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  • 1.
    Aglago, Elom K.
    et al.
    Nutrition and Metabolism Branch, International Agency for Research on Cancer, Lyon, France; Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom.
    Cross, Amanda J.
    Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom.
    Riboli, Elio
    Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom.
    Fedirko, Veronika
    Department of Epidemiology, University of Texas M. D. Anderson Cancer Center, TX, Houston, United States; Department of Epidemiology, Rollins School of Public Health, Emory University, GA, Atlanta, United States.
    Hughes, David J.
    Cancer Biology and Therapeutics Group (CBT), Conway Institute, School of Biomolecular and Biomedical Science (SBBS), University College Dublin, Dublin, Ireland.
    Fournier, Agnes
    Centre de Recherche en Epidémiologie et Santé des Populations, Université Paris-Sud, UVSQ, INSERM, Université Paris-Saclay, Villejuif, France; Institut Gustave Roussy, Villejuif, France.
    Jakszyn, Paula
    Unit of Nutrition and Cancer, Cancer Epidemiology Research Programme, Catalan Institute of Oncology (ICO-IDIBELL), Barcelona, Spain; Blanquerna School of Health Sciences, Ramon Llull University, Barcelona, Spain.
    Freisling, Heinz
    Nutrition and Metabolism Branch, International Agency for Research on Cancer, Lyon, France.
    Gunter, Marc J.
    Nutrition and Metabolism Branch, International Agency for Research on Cancer, Lyon, France.
    Dahm, Christina C.
    Department of Public Health, Aarhus University, Aarhus, Denmark.
    Overvad, Kim
    Department of Public Health, Aarhus University, Aarhus, Denmark; Department of Cardiology, Aalborg University Hospital, Aalborg, Denmark.
    Tjønneland, Anne
    Danish Cancer Society Research Center, Copenhagen, Denmark; Department of Public Health, Section of Environmental Health, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
    Kyrø, Cecilie
    Danish Cancer Society Research Center, Copenhagen, Denmark.
    Boutron-Ruault, Marie-Christine
    Centre de Recherche en Epidémiologie et Santé des Populations, Université Paris-Sud, UVSQ, INSERM, Université Paris-Saclay, Villejuif, France; Institut Gustave Roussy, Villejuif, France.
    Rothwell, Joseph A.
    Centre de Recherche en Epidémiologie et Santé des Populations, Université Paris-Sud, UVSQ, INSERM, Université Paris-Saclay, Villejuif, France; Institut Gustave Roussy, Villejuif, France.
    Severi, Gianluca
    Centre de Recherche en Epidémiologie et Santé des Populations, Université Paris-Sud, UVSQ, INSERM, Université Paris-Saclay, Villejuif, France; Institut Gustave Roussy, Villejuif, France; Department of Statistics, Computer Science, Applications “G. Parenti”, University of Florence, Florence, Italy.
    Katzke, Verena
    Division of Cancer Epidemiology, German Cancer research Center (DKFZ), Heidelberg, Germany.
    Srour, Bernard
    Division of Cancer Epidemiology, German Cancer research Center (DKFZ), Heidelberg, Germany.
    Schulze, Matthias B.
    Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany; Institute of Nutritional Science, University of Potsdam, Potsdam, Germany.
    Wittenbecher, Clemens
    Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany; Department of Nutrition, Harvard T.H. Chan School of Public Health, MA, Boston, United States; German Center for Diabetes Research (DZD), Neuherberg, Germany.
    Palli, Domenico
    Cancer Risk Factors and Life-Style Epidemiology Unit, Institute for Cancer Research, Prevention and Clinical Network, ISPRO, Florence, Italy.
    Sieri, Sabina
    Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Via Venezian, Milano, Italy.
    Pasanisi, Fabrizio
    Internal Medicine and Clinical Nutrition Unit, Department of Clinical Medicine and Surgery, Federico II University Hospital, Naples, Italy.
    Tumino, Rosario
    Hyblean Association for Epidemiological Research, AIRE-ONLUS, Ragusa, Italy.
    Ricceri, Fulvio
    Department of Clinical and Biological Sciences, University of Turin, Turin, Italy; Unit of Epidemiology, Regional Health Service, TO, Grugliasco, Italy.
    Bueno-de-Mesquita, Bas
    Former senior scientist, Department for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment (RIVM), PO Box 1, Bilthoven, Netherlands.
    Derksen, Jeroen W. G.
    Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands.
    Skeie, Guri
    Faculty of Health Sciences, Department of Community Medicine, University of Tromsø, The Arctic University of Norway, Tromsø, Norway.
    Jensen, Torill Enget
    Faculty of Health Sciences, Department of Community Medicine, University of Tromsø, The Arctic University of Norway, Tromsø, Norway.
    Lukic, Marko
    Faculty of Health Sciences, Department of Community Medicine, University of Tromsø, The Arctic University of Norway, Tromsø, Norway.
    Sánchez, Maria-Jose
    Escuela Andaluza de Salud Pública (EASP), Granada, Spain; Instituto de Investigación Biosanitaria ibs.GRANADA, Granada, Spain; Department of Preventive Medicine and Public Health, University of Granada, Granada, Spain; Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain.
    Amiano, Pilar
    Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain; Ministry of Health of the Basque Government, Sub-Directorate for Public Health and Addictions of Gipuzkoa, San Sebastián, Spain; Biodonostia Health Research Institute, Epidemiology and Public Health Area, San Sebastián, Spain.
    Colorado-Yohar, Sandra
    Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain; Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca, Murcia, Spain; Research Group on Demography and Health, National Faculty of Public Health, University of Antioquia, Medellín, Colombia.
    Barricarte, Aurelio
    Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain; Navarra Public Health Institute, Pamplona, Spain; Navarra Institute for Health Research (IdiSNA), Pamplona, Spain.
    Ericson, Ulrika
    Department of Clinical Sciences in Malmö, Lund University, Malmö, Sweden.
    van Guelpen, Bethany
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper. Umeå universitet, Medicinska fakulteten, Wallenberg centrum för molekylär medicin vid Umeå universitet (WCMM).
    Papier, Keren
    Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.
    Knuppel, Anika
    Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.
    Casagrande, Corinne
    Nutrition and Metabolism Branch, International Agency for Research on Cancer, Lyon, France.
    Huybrechts, Inge
    Nutrition and Metabolism Branch, International Agency for Research on Cancer, Lyon, France.
    Heath, Alicia K.
    Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom.
    Tsilidis, Konstantinos K.
    Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom.
    Jenab, Mazda
    Nutrition and Metabolism Branch, International Agency for Research on Cancer, Lyon, France.
    Dietary intake of total, heme and non-heme iron and the risk of colorectal cancer in a European prospective cohort study2023Ingår i: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 128, s. 1529-1540Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Iron is an essential micronutrient with differing intake patterns and metabolism between men and women. Epidemiologic evidence on the association of dietary iron and its heme and non-heme components with colorectal cancer (CRC) development is inconclusive.

    Methods: We examined baseline dietary questionnaire-assessed intakes of total, heme, and non-heme iron and CRC risk in the EPIC cohort. Sex-specific multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were computed using Cox regression. We modelled substitution of a 1 mg/day of heme iron intake with non-heme iron using the leave one-out method.

    Results: Of 450,105 participants (318,680 women) followed for 14.2 ± 4.0 years, 6162 (3511 women) developed CRC. In men, total iron intake was not associated with CRC risk (highest vs. lowest quintile, HRQ5vs.Q1:0.88; 95%CI:0.73, 1.06). An inverse association was observed for non-heme iron (HRQ5vs.Q1:0.80, 95%CI:0.67, 0.96) whereas heme iron showed a non-significant association (HRQ5vs.Q1:1.10; 95%CI:0.96, 1.27). In women, CRC risk was not associated with intakes of total (HRQ5vs.Q1:1.11, 95%CI:0.94, 1.31), heme (HRQ5vs.Q1:0.95; 95%CI:0.84, 1.07) or non-heme iron (HRQ5vs.Q1:1.03, 95%CI:0.88, 1.20). Substitution of heme with non-heme iron demonstrated lower CRC risk in men (HR:0.94; 95%CI: 0.89, 0.99).

    Conclusions: Our findings suggest potential sex-specific CRC risk associations for higher iron consumption that may differ by dietary sources.

  • 2. Aglago, Elom K.
    et al.
    Huybrechts, Inge
    Murphy, Neil
    Casagrande, Corinne
    Nicolas, Genevieve
    Pischon, Tobias
    Fedirko, Veronika
    Severi, Gianluca
    Boutron-Ruault, Marie-Christine
    Fournier, Agnès
    Katzke, Verena
    Kühn, Tilman
    Olsen, Anja
    Tjønneland, Anne
    Dahm, Christina C.
    Overvad, Kim
    Lasheras, Cristina
    Agudo, Antonio
    Sánchez, Maria-Jose
    Amiano, Pilar
    Huerta, José Maria
    Ardanaz, Eva
    Perez-Cornago, Aurora
    Trichopoulou, Antonia
    Karakatsani, Anna
    Martimianaki, Georgia
    Palli, Domenico
    Pala, Valeria
    Tumino, Rosario
    Naccarati, Alessio
    Panico, Salvatore
    Bueno-de-Mesquita, Bas
    May, Anne
    Derksen, Jeroen W. G.
    Hellstrand, Sophie
    Ohlsson, Bodil
    Wennberg, Maria
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för hållbar hälsa.
    van Guelpen, Bethany
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Skeie, Guri
    Brustad, Magritt
    Weiderpass, Elisabete
    Cross, Amanda J.
    Ward, Heather
    Riboli, Elio
    Norat, Teresa
    Chajes, Veronique
    Gunter, Marc J.
    Consumption of Fish and Long-chain n-3 Polyunsaturated Fatty Acids Is Associated With Reduced Risk of Colorectal Cancer in a Large European Cohort2020Ingår i: Clinical Gastroenterology and Hepatology, ISSN 1542-3565, E-ISSN 1542-7714, s. 654-666Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND & AIMS: There is an unclear association between intake of fish and long-chain n-3 polyunsaturated fatty acids (n-3 LC-PUFAs) and colorectal cancer (CRC). We examined the association between fish consumption, dietary and circulating levels of n-3 LC-PUFAs, and ratio of n-6:n-3 LC-PUFA with CRC using data from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.

    METHODS: Dietary intake of fish (total, fatty/oily, lean/white) and n-3 LC-PUFA were estimated by food frequency questionnaires given to 521,324 participants in the EPIC study; among these, 6291 individuals developed CRC (median follow up, 14.9 years). Levels of phospholipid LC-PUFA were measured by gas chromatography in plasma samples from a sub-group of 461 CRC cases and 461 matched individuals without CRC (controls). Multivariable Cox proportional hazards and conditional logistic regression models were used to calculate hazard ratios (HRs) and odds ratios (ORs), respectively, with 95% CIs.

    RESULTS: Total intake of fish (HR for quintile 5 vs 1, 0.88; 95% CI, 0.80-0.96; Ptrend = .005), fatty fish (HR for quintile 5 vs 1, 0.90; 95% CI, 0.82-0.98; Ptrend = .009), and lean fish (HR for quintile 5 vs 1, 0.91; 95% CI, 0.83-1.00; Ptrend = .016) were inversely associated with CRC incidence. Intake of total n-3 LC-PUFA (HR for quintile 5 vs 1, 0.86; 95% CI, 0.78-0.95; Ptrend = .010) was also associated with reduced risk of CRC, whereas dietary ratio of n-6:n-3 LC-PUFA was associated with increased risk of CRC (HR for quintile 5 vs 1, 1.31; 95% CI, 1.18-1.45; Ptrend < .001). Plasma levels of phospholipid n-3 LC-PUFA was not associated with overall CRC risk, but an inverse trend was observed for proximal compared with distal colon cancer (Pheterogeneity = .026).

    CONCLUSIONS: In an analysis of dietary patterns of participants in the EPIC study, we found regular consumption of fish, at recommended levels, to be associated with a lower risk of CRC, possibly through exposure to n-3 LC-PUFA. Levels of n-3 LC-PUFA in plasma were not associated with CRC risk, but there may be differences in risk at different regions of the colon.

  • 3.
    Aglago, Elom K.
    et al.
    Department of Epidemiology and Biostatistics, Imperial College London, School of Public Health, London, United Kingdom.
    Kim, Andre
    Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, CA, Los Angeles, United States.
    Lin, Yi
    Public Health Sciences Division, Fred Hutchinson Cancer Research Center, WA, Seattle, United States.
    Qu, Conghui
    Public Health Sciences Division, Fred Hutchinson Cancer Research Center, WA, Seattle, United States.
    Evangelou, Marina
    Department of Epidemiology and Biostatistics, Imperial College London, School of Public Health, London, United Kingdom.
    Ren, Yu
    Department of Epidemiology and Biostatistics, Imperial College London, School of Public Health, London, United Kingdom.
    Morrison, John
    Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, CA, Los Angeles, United States.
    Albanes, Demetrius
    Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, MD, Bethesda, Liberia.
    Arndt, Volker
    Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.
    Barry, Elizabeth L.
    Department of Epidemiology, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire.
    Baurley, James W.
    Bioinformatics and Data Science Research Center, Bina Nusantara University, Jakarta, Indonesia.
    Berndt, Sonja I.
    Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, MD, Bethesda, Liberia.
    Bien, Stephanie A.
    Public Health Sciences Division, Fred Hutchinson Cancer Research Center, WA, Seattle, United States.
    Bishop, D Timothy
    Leeds Institute of Cancer and Pathology, University of Leeds, Leeds, United Kingdom.
    Bouras, Emmanouil
    Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece.
    Brenner, Hermann
    Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany; Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany; German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.
    Buchanan, Daniel D.
    Colorectal Oncogenomics Group, Department of Clinical Pathology, University of Melbourne, VIC, Parkville, Australia; University of Melbourne Centre for Cancer Research, Victorian Comprehensive Cancer Centre, VIC, Parkville, Australia; Genomic Medicine and Family Cancer Clinic, Royal Melbourne Hospital, VIC, Parkville, Australia.
    Budiarto, Arif
    Bioinformatics and Data Science Research Center, Bina Nusantara University, Jakarta, Indonesia; Computer Science Department, School of Computer Science, Bina Nusantara University, Jakarta, Indonesia.
    Carreras-Torres, Robert
    ONCOBELL Program, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain; Digestive Diseases and Microbiota Group, Girona Biomedical Research Institute (IDIBGI), Salt, Girona, Spain.
    Casey, Graham
    Center for Public Health Genomics, Department of Public Health Sciences, University of Virginia, VA, Charlottesville, United States.
    Cenggoro, Tjeng Wawan
    Bioinformatics and Data Science Research Center, Bina Nusantara University, Jakarta, Indonesia.
    Chan, Andrew T.
    Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, MA, Boston, United States; Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, MA, Boston, United States; Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, MA, Boston, United States; Broad Institute of Harvard and MIT, MA, Cambridge, United States; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Harvard University, MA, Boston, United States; Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Harvard University, MA, Boston, United States.
    Chang-Claude, Jenny
    Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany; University Medical Centre Hamburg-Eppendorf, University Cancer Centre Hamburg (UCCH), Hamburg, Germany.
    Chen, Xuechen
    Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany; Medical Faculty Heidelberg, Heidelberg University, Heidelberg, Germany.
    Conti, David V.
    Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, CA, Los Angeles, United States.
    Devall, Matthew
    Department of Family Medicine, University of Virginia, VA, Charlottesville, United States.
    Diez-Obrero, Virginia
    ONCOBELL Program, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain; Unit of Biomarkers and Susceptibility (UBS), Oncology Data Analytics Program (ODAP), Catalan Institute of Oncology (ICO), L'Hospitalet del Llobregat, Barcelona, Spain; Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), Madrid, Spain; Department of Clinical Sciences, Faculty of Medicine, University of Barcelona, Barcelona, Spain; Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.
    Dimou, Niki
    Nutrition and Metabolism Branch, International Agency for Research on Cancer, World Health Organization, Lyon, France.
    Drew, David
    Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, MA, Boston, United States.
    Figueiredo, Jane C.
    Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, CA, Los Angeles, United States; Department of Medicine, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, CA, Los Angeles, United States.
    Gallinger, Steven
    Lunenfeld Tanenbaum Research Institute, University of Toronto, Mount Sinai Hospital, ON, Toronto, Canada.
    Giles, Graham G.
    Cancer Epidemiology Division, Cancer Council Victoria, VIC, Melbourne, Australia; Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Melbourne, Australia; Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, VIC, Clayton, Australia.
    Gruber, Stephen B.
    Department of Medical Oncology & Therapeutics Research, City of Hope National Medical Center.
    Gsur, Andrea
    Center for Cancer Research, Medical University of Vienna, Vienna, Austria.
    Gunter, Marc J.
    Nutrition and Metabolism Branch, International Agency for Research on Cancer, World Health Organization, Lyon, France.
    Hampel, Heather
    Department of Medical Oncology & Therapeutics Research, City of Hope National Medical Center.
    Harlid, Sophia
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Hidaka, Akihisa
    Public Health Sciences Division, Fred Hutchinson Cancer Research Center, WA, Seattle, United States.
    Harrison, Tabitha A.
    Public Health Sciences Division, Fred Hutchinson Cancer Research Center, WA, Seattle, United States.
    Hoffmeister, Michael
    Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.
    Huyghe, Jeroen R.
    Public Health Sciences Division, Fred Hutchinson Cancer Research Center, WA, Seattle, United States.
    Jenkins, Mark A.
    Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Melbourne, Australia.
    Jordahl, Kristina
    Public Health Sciences Division, Fred Hutchinson Cancer Research Center, WA, Seattle, United States.
    Joshi, Amit D.
    Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, MA, Boston, United States; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Harvard University, MA, Boston, United States.
    Kawaguchi, Eric S.
    Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, CA, Los Angeles, United States.
    Keku, Temitope O.
    Center for Gastrointestinal Biology and Disease, University of North Carolina, Chapel Hill, NC, United States.
    Kundaje, Anshul
    Department of Genetics, Stanford University, CA, Stanford, United States; Department of Computer Science, Stanford University, CA, Stanford, United States.
    Larsson, Susanna C.
    Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Marchand, Loic Le
    University of Hawaii Cancer Center, HI, Honolulu, United States.
    Lewinger, Juan Pablo
    Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, CA, Los Angeles, United States.
    Li, Li
    Department of Family Medicine, University of Virginia, VA, Charlottesville, United States.
    Lynch, Brigid M.
    Cancer Epidemiology Division, Cancer Council Victoria, VIC, Melbourne, Australia; Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Melbourne, Australia; Physical Activity Laboratory, Baker Heart and Diabetes Institute, Melbourne, Australia.
    Mahesworo, Bharuno
    Bioinformatics and Data Science Research Center, Bina Nusantara University, Jakarta, Indonesia.
    Mandic, Marko
    Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany; Medical Faculty Heidelberg, Heidelberg University, Heidelberg, Germany.
    Obón-Santacana, Mireia
    ONCOBELL Program, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain; Unit of Biomarkers and Susceptibility (UBS), Oncology Data Analytics Program (ODAP), Catalan Institute of Oncology (ICO), L'Hospitalet del Llobregat, Barcelona, Spain; Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), Madrid, Spain.
    Moreno, Victor
    ONCOBELL Program, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain; Unit of Biomarkers and Susceptibility (UBS), Oncology Data Analytics Program (ODAP), Catalan Institute of Oncology (ICO), L'Hospitalet del Llobregat, Barcelona, Spain; Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), Madrid, Spain; Department of Clinical Sciences, Faculty of Medicine, University of Barcelona, Barcelona, Spain.
    Murphy, Neil
    Nutrition and Metabolism Branch, International Agency for Research on Cancer, World Health Organization, Lyon, France.
    Nan, Hongmei
    Department of Epidemiology, Richard M. Fairbanks School of Public Health, IN, Indianapolis, United States; IU Melvin and Bren Simon Cancer Center, Indiana University, IN, Indianapolis, United States.
    Nassir, Rami
    Department of Pathology, School of Medicine, Umm Al-Qura'a University, Mecca, Saudi Arabia.
    Newcomb, Polly A.
    Public Health Sciences Division, Fred Hutchinson Cancer Research Center, WA, Seattle, United States; Department of Epidemiology, University of Washington School of Public Health, WA, Seattle, United States.
    Ogino, Shuji
    Broad Institute of Harvard and MIT, MA, Cambridge, United States; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Harvard University, MA, Boston, United States; Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, MA, Boston, United States; Department of Oncologic Pathology, Dana-Farber Cancer Institute, MA, Boston, United States.
    Ose, Jennifer
    Huntsman Cancer Institute, UT, Salt Lake City, United States; Department of Population Health Sciences, University of Utah, UT, Salt Lake City, United States.
    Pai, Rish K.
    Department of Laboratory Medicine and Pathology, Mayo Clinic Arizona, AZ, Scottsdale, United States.
    Palmer, Julie R.
    Department of Medicine, Boston University School of Medicine, Slone Epidemiology Center, Boston University, MA, Boston, United States.
    Papadimitriou, Nikos
    Nutrition and Metabolism Branch, International Agency for Research on Cancer, World Health Organization, Lyon, France.
    Pardamean, Bens
    Bioinformatics and Data Science Research Center, Bina Nusantara University, Jakarta, Indonesia.
    Peoples, Anita R.
    Huntsman Cancer Institute, UT, Salt Lake City, United States; Department of Population Health Sciences, University of Utah, UT, Salt Lake City, United States.
    Platz, Elizabeth A.
    Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, MD, Baltimore, Liberia.
    Potter, John D.
    Public Health Sciences Division, Fred Hutchinson Cancer Research Center, WA, Seattle, United States; Department of Epidemiology, University of Washington School of Public Health, WA, Seattle, United States; Research Centre for Hauora and Health, Massey University, Wellington, New Zealand.
    Prentice, Ross L.
    Public Health Sciences Division, Fred Hutchinson Cancer Research Center, WA, Seattle, United States.
    Rennert, Gad
    Department of Community Medicine and Epidemiology, Lady Davis Carmel Medical Center, Haifa, Israel; Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel; Clalit National Cancer Control Center, Haifa, Israel.
    Ruiz-Narvaez, Edward
    Department of Nutritional Sciences, University of Michigan School of Public Health, MI, Ann Arbor, United States.
    Sakoda, Lori C.
    Public Health Sciences Division, Fred Hutchinson Cancer Research Center, WA, Seattle, United States; Division of Research, Kaiser Permanente Northern California, CA, Oakland, United States.
    Scacheri, Peter C.
    Department of Genetics and Genome Sciences, Case Western Reserve University, OH, Cleveland, United States.
    Schmit, Stephanie L.
    Genomic Medicine Institute, Cleveland Clinic, OH, Cleveland, United States.
    Schoen, Robert E.
    Department of Medicine and Epidemiology, University of Pittsburgh Medical Center, PA, Pittsburgh, United States.
    Shcherbina, Anna
    Department of Genetics, Stanford University, CA, Stanford, United States; Department of Computer Science, Stanford University, CA, Stanford, United States.
    Slattery, Martha L.
    Department of Internal Medicine, University of Utah, UT, Salt Lake City, United States.
    Stern, Mariana C.
    Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, CA, Los Angeles, United States.
    Su, Yu-Ru
    Public Health Sciences Division, Fred Hutchinson Cancer Research Center, WA, Seattle, United States.
    Tangen, Catherine M.
    SWOG Statistical Center, Fred Hutchinson Cancer Research Center, WA, Seattle, United States.
    Thibodeau, Stephen N.
    Division of Laboratory Genetics, Department of Laboratory Medicine and Pathology, Mayo Clinic, MN, Rochester, United States.
    Thomas, Duncan C.
    Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, CA, Los Angeles, United States.
    Tian, Yu
    Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany; School of Public Health, Capital Medical University, Beijing, China.
    Ulrich, Cornelia M.
    Huntsman Cancer Institute, UT, Salt Lake City, United States; Department of Population Health Sciences, University of Utah, UT, Salt Lake City, United States.
    van Duijnhoven, Franzel Jb
    Division of Human Nutrition and Health, Wageningen University & Research, Wageningen, Netherlands.
    van Guelpen, Bethany
    Umeå universitet, Medicinska fakulteten, Wallenberg centrum för molekylär medicin vid Umeå universitet (WCMM). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Visvanathan, Kala
    Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, MD, Baltimore, Liberia.
    Vodicka, Pavel
    Department of Molecular Biology of Cancer, Institute of Experimental Medicine of the Czech Academy of Sciences, Prague, Czech Republic; Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University, Prague, Czech Republic; Faculty of Medicine and Biomedical Center in Pilsen, Charles University, Pilsen, Czech Republic.
    Wang, Jun
    Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, CA, Los Angeles, United States.
    White, Emily
    Public Health Sciences Division, Fred Hutchinson Cancer Research Center, WA, Seattle, United States; Department of Epidemiology, University of Washington School of Public Health, WA, Seattle, United States.
    Wolk, Alicja
    Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Woods, Michael O.
    Memorial University of Newfoundland, Discipline of Genetics, St. John's, Canada.
    Wu, Anna H.
    Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, CA, Los Angeles, United States.
    Zemlianskaia, Natalia
    Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, CA, Los Angeles, United States.
    Hsu, Li
    Public Health Sciences Division, Fred Hutchinson Cancer Research Center, WA, Seattle, United States; Department of Biostatistics, University of Washington, WA, Seattle, United States.
    Gauderman, W James
    Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, CA, Los Angeles, United States.
    Peters, Ulrike
    Public Health Sciences Division, Fred Hutchinson Cancer Research Center, WA, Seattle, United States; Department of Epidemiology, University of Washington School of Public Health, WA, Seattle, United States.
    Tsilidis, Konstantinos K.
    Department of Epidemiology and Biostatistics, Imperial College London, School of Public Health, London, United Kingdom; Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece.
    Campbell, Peter T.
    Department of Epidemiology and Population Health, Albert Einstein College of Medicine, NY, Bronx, United States.
    A Genetic Locus within the FMN1/GREM1 Gene Region Interacts with Body Mass Index in Colorectal Cancer Risk2023Ingår i: Cancer Research, ISSN 0008-5472, E-ISSN 1538-7445, Vol. 83, nr 15, s. 2572-2583Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Colorectal cancer risk can be impacted by genetic, environmental, and lifestyle factors, including diet and obesity. Gene-environment interactions (G × E) can provide biological insights into the effects of obesity on colorectal cancer risk. Here, we assessed potential genome-wide G × E interactions between body mass index (BMI) and common SNPs for colorectal cancer risk using data from 36,415 colorectal cancer cases and 48,451 controls from three international colorectal cancer consortia (CCFR, CORECT, and GECCO). The G × E tests included the conventional logistic regression using multiplicative terms (one degree of freedom, 1DF test), the two-step EDGE method, and the joint 3DF test, each of which is powerful for detecting G × E interactions under specific conditions. BMI was associated with higher colorectal cancer risk. The two-step approach revealed a statistically significant G×BMI interaction located within the Formin 1/Gremlin 1 (FMN1/GREM1) gene region (rs58349661). This SNP was also identified by the 3DF test, with a suggestive statistical significance in the 1DF test. Among participants with the CC genotype of rs58349661, overweight and obesity categories were associated with higher colorectal cancer risk, whereas null associations were observed across BMI categories in those with the TT genotype. Using data from three large international consortia, this study discovered a locus in the FMN1/GREM1 gene region that interacts with BMI on the association with colorectal cancer risk. Further studies should examine the potential mechanisms through which this locus modifies the etiologic link between obesity and colorectal cancer.

    SIGNIFICANCE: This gene-environment interaction analysis revealed a genetic locus in FMN1/GREM1 that interacts with body mass index in colorectal cancer risk, suggesting potential implications for precision prevention strategies.

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  • 4. Aleksandrova, Krasimira
    et al.
    Jenab, Mazda
    Leitzmann, Michael
    Bueno-de-Mesquita, Bas
    Kaaks, Rudolf
    Trichopoulou, Antonia
    Bamia, Christina
    Lagiou, Pagona
    Rinaldi, Sabina
    Freisling, Heinz
    Carayol, Marion
    Pischon, Tobias
    Drogan, Dagmar
    Weiderpass, Elisabete
    Jakszyn, Paula
    Overvad, Kim
    Dahm, Christina C.
    Tjonneland, Anne
    Bouton-Ruault, Marie-Christine
    Kuehn, Tilman
    Peppa, Eleni
    Valanou, Elissavet
    La Vecchia, Carlo
    Palli, Domenico
    Panico, Salvatore
    Sacerdote, Carlotta
    Agnoli, Claudia
    Tumino, Rosario
    May, Anne
    van Vulpen, Jonna
    Borch, Kristin Benjaminsen
    Oyeyemi, Sunday Oluwafemi
    Ramon Quiros, J.
    Bonet, Catalina
    Sanchez, Maria-Jose
    Dorronsoro, Miren
    Navarro, Carmen
    Barricarte, Aurelio
    van Guelpen, Bethany
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Wennberg, Patrik
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Key, Timothy J.
    Khaw, Kay-Tee
    Wareham, Nicholas
    Assi, Nada
    Ward, Heather A.
    Aune, Dagfinn
    Riboli, Elio
    Boeing, Heiner
    Physical activity, mediating factors and risk of colon cancer: insights into adiposity and circulating biomarkers from the EPIC cohort2017Ingår i: International Journal of Epidemiology, ISSN 0300-5771, E-ISSN 1464-3685, Vol. 46, nr 6, s. 1823-1835Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    There is convincing evidence that high physical activity lowers the risk of colon cancer; however, the underlying biological mechanisms remain largely unknown. We aimed to determine the extent to which body fatness and biomarkers of various biologically plausible pathways account for the association between physical activity and colon cancer. We conducted a nested case-control study in a cohort of 519 978 men and women aged 25 to 70 years followed from 1992 to 2003. A total of 713 incident colon cancer cases were matched, using risk-set sampling, to 713 controls on age, sex, study centre, fasting status and hormonal therapy use. The amount of total physical activity during the past year was expressed in metabolic equivalent of task [MET]-h/week. Anthropometric measurements and blood samples were collected at study baseline. High physical activity was associated with a lower risk of colon cancer: relative risk a parts per thousand<yen>91 MET-h/week vs < 91 MET-h/week = 0.75 [95% confidence interval (CI): 0.57 to 0.96]. In mediation analyses, this association was accounted for by waist circumference: proportion explained effect (PEE) = 17%; CI: 4% to 52%; and the biomarkers soluble leptin receptor (sOB-R): PEE = 15%; 95% CI: 1% to 50% and 5-hydroxyvitamin D (25[OH]D): PEE = 30%; 95% CI: 12% to 88%. In combination, these factors explained 45% (95% CI: 20% to 125%) of the association. Beyond waist circumference, sOB-R and 25[OH]D additionally explained 10% (95% CI: 1%; 56%) and 23% (95% CI: 6%; 111%) of the association, respectively. Promoting physical activity, particularly outdoors, and maintaining metabolic health and adequate vitamin D levels could represent a promising strategy for colon cancer prevention.

  • 5. Aleksandrova, Krasimira
    et al.
    Reichmann, Robin
    Kaaks, Rudolf
    Jenab, Mazda
    Bueno-de-Mesquita, H. Bas
    Dahm, Christina C.
    Eriksen, Anne Kirstine
    Tjonneland, Anne
    Artaud, Fanny
    Boutron-Ruault, Marie-Christine
    Severi, Gianluca
    Husing, Anika
    Trichopoulou, Antonia
    Karakatsani, Anna
    Peppa, Eleni
    Panico, Salvatore
    Masala, Giovanna
    Grioni, Sara
    Sacerdote, Carlotta
    Tumino, Rosario
    Elias, Sjoerd G.
    May, Anne M.
    Borch, Kristin B.
    Sandanger, Torkjel M.
    Skeie, Guri
    Sanchez, Maria-Jose
    Huerta, Jose Maria
    Sala, Nuria
    Gurrea, Aurelio Barricarte
    Quiros, Jose Ramon
    Amiano, Pilar
    Berntsson, Jonna
    Drake, Isabel
    van Guelpen, Bethany
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi. Umeå universitet, Medicinska fakulteten, Wallenberg centrum för molekylär medicin vid Umeå universitet (WCMM).
    Harlid, Sophia
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Key, Tim
    Weiderpass, Elisabete
    Aglago, Elom K.
    Cross, Amanda J.
    Tsilidis, Konstantinos K.
    Riboli, Elio
    Gunter, Marc J.
    Development and validation of a lifestyle-based model for colorectal cancer risk prediction: the LiFeCRC score2021Ingår i: BMC Medicine, E-ISSN 1741-7015, Vol. 19, nr 1, artikel-id 1Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Nutrition and lifestyle have been long established as risk factors for colorectal cancer (CRC). Modifiable lifestyle behaviours bear potential to minimize long-term CRC risk; however, translation of lifestyle information into individualized CRC risk assessment has not been implemented. Lifestyle-based risk models may aid the identification of high-risk individuals, guide referral to screening and motivate behaviour change. We therefore developed and validated a lifestyle-based CRC risk prediction algorithm in an asymptomatic European population.

    Methods: The model was based on data from 255,482 participants in the European Prospective Investigation into Cancer and Nutrition (EPIC) study aged 19 to 70 years who were free of cancer at study baseline (1992–2000) and were followed up to 31 September 2010. The model was validated in a sample comprising 74,403 participants selected among five EPIC centres. Over a median follow-up time of 15 years, there were 3645 and 981 colorectal cancer cases in the derivation and validation samples, respectively. Variable selection algorithms in Cox proportional hazard regression and random survival forest (RSF) were used to identify the best predictors among plausible predictor variables. Measures of discrimination and calibration were calculated in derivation and validation samples. To facilitate model communication, a nomogram and a web-based application were developed.

    Results: The final selection model included age, waist circumference, height, smoking, alcohol consumption, physical activity, vegetables, dairy products, processed meat, and sugar and confectionary. The risk score demonstrated good discrimination overall and in sex-specific models. Harrell’s C-index was 0.710 in the derivation cohort and 0.714 in the validation cohort. The model was well calibrated and showed strong agreement between predicted and observed risk. Random survival forest analysis suggested high model robustness. Beyond age, lifestyle data led to improved model performance overall (continuous net reclassification improvement = 0.307 (95% CI 0.264–0.352)), and especially for young individuals below 45 years (continuous net reclassification improvement = 0.364 (95% CI 0.084–0.575)).

    Conclusions: LiFeCRC score based on age and lifestyle data accurately identifies individuals at risk for incident colorectal cancer in European populations and could contribute to improved prevention through motivating lifestyle change at an individual level.

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  • 6.
    Alwers, Elizabeth
    et al.
    Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany.
    Carr, Prudence R.
    Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany.
    Banbury, Barbara
    Public Health Sciences Division, Fred Hutchinson Cancer Research Center, WA, Seattle, United States.
    Walter, Viola
    Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany.
    Chang-Claude, Jenny
    Division of Cancer Epidemiology, German Cancer Research Center, Heidelberg, Germany; Genetic Tumor Epidemiology Group, University Medical Center Hamburg-Eppendorf, University Cancer Center Hamburg, Hamburg, Germany.
    Jansen, Lina
    Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany.
    Drew, David A.
    Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, Harvard Medical School, MA, Boston, United States; Division of Gastroenterology, Massachusetts General Hospital, Harvard Medical School, MA, Boston, United States.
    Giovannucci, Edward
    Department of Epidemiology, Harvard T.H. Chan School of Public Health, Harvard University, MA, Boston, United States; Department of Nutrition, Harvard T.H. Chan School of Public Health, Harvard University, MA, Boston, United States; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, MA, Boston, United States.
    Nan, Hongmei
    Department of Global Health, Richard M. Fairbanks School of Public Health, IN, Indianapolis, United States.
    Berndt, Sonja I.
    Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, MD, Bethesda, United States.
    Huang, Wen-Yi
    Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, MD, Bethesda, United States.
    Prizment, Anna
    Division of Epidemiology and Community Health, University of Minnesota, MN, Minneapolis, United States.
    Hayes, Richard B.
    Division of Epidemiology, Department of Population Health, New York University, School of Medicine, NY, New York, United States.
    Sakoda, Lori C.
    Division of Research, Kaiser Permanente Northern California, CA, Oakland, United States.
    White, Emily
    Public Health Sciences Division, Fred Hutchinson Cancer Research Center, WA, Seattle, United States.
    Labadie, Julia
    Public Health Sciences Division, Fred Hutchinson Cancer Research Center, WA, Seattle, United States; Department of Epidemiology, University of Washington, School of Public Health, WA, Seattle, United States.
    Slattery, Martha
    Department of Internal Medicine, University of Utah, UT, Salt Lake City, United States.
    Schoen, Robert E.
    Departments of Medicine and Epidemiology, University of Pittsburgh, PA, Pittsburgh, United States.
    Diergaarde, Brenda
    Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, PA, United States; UPMC Hillman Cancer Center, PA, Pittsburgh, United States.
    van Guelpen, Bethany
    Umeå universitet, Medicinska fakulteten, Wallenberg centrum för molekylär medicin vid Umeå universitet (WCMM). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Campbell, Peter T.
    Department of Population Science, American Cancer Society, GA, Atlanta, United States.
    Peters, Ulrike
    Public Health Sciences Division, Fred Hutchinson Cancer Research Center, WA, Seattle, United States; Department of Epidemiology, University of Washington, School of Public Health, WA, Seattle, United States.
    Chan, Andrew T.
    Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, Harvard Medical School, MA, Boston, United States; Division of Gastroenterology, Massachusetts General Hospital, Harvard Medical School, MA, Boston, United States; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Harvard University, MA, Boston, United States; Broad Institute of Harvard and MIT, MA, Cambridge, United States.
    Newcomb, Polly A.
    Public Health Sciences Division, Fred Hutchinson Cancer Research Center, WA, Seattle, United States.
    Hoffmeister, Michael
    Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany.
    Brenner, Hermann
    Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany; Division of Preventive Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany; German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.
    Smoking Behavior and Prognosis after Colorectal Cancer Diagnosis: A Pooled Analysis of 11 Studies2021Ingår i: JNCI Cancer Spectrum, E-ISSN 2515-5091, Vol. 5, nr 5, artikel-id pkab077Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Smoking has been associated with colorectal cancer (CRC) incidence and mortality in previous studies, but current evidence on smoking in association with survival after CRC diagnosis is limited.

    Methods: We pooled data from 12 345 patients with stage I-IV CRC from 11 epidemiologic studies in the International Survival Analysis in Colorectal Cancer Consortium. Cox proportional hazards regression models were used to evaluate the associations of prediagnostic smoking behavior with overall, CRC-specific, and non-CRC-specific survival.

    Results: Among 12 345 patients with CRC, 4379 (35.5%) died (2515 from CRC) over a median follow-up time of 7.5years. Smoking was strongly associated with worse survival in stage I-III patients, whereas no associa-tion was observed among stage IV patients. Among stage I-III patients, clear dose-response relationships with all survival outcomes were seen for current smokers. For example, current smokers with 40 or more pack-years had statistically significantly worse over-all, CRC-specific, and non-CRC-specific survival compared with never smokers (hazard ratio [HR] 1/41.94, 95% confidence interval [CI] 1/41.68 to 2.25; HR = 1.41, 95% CI = 1.12 to 1.78; and HR = 2.67, 95% CI = 2.19 to 3.26, respectively). Similar associations with all sur-vival outcomes were observed for former smokers who had quit for less than 10years, but only a weak association with non-CRC-specific survival was seen among former smokers who had quit for more than 10years.

    Conclusions: This large consortium of CRC patient studies provides compelling evidence that smoking is strongly associated with worse survival of stage I-III CRC patients in a clear dose-response manner. The detrimental effect of smoking was primarily related to noncolorectal cancer events, but current heavy smoking also showed an association with CRC-specific survival.

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  • 7.
    Amadou, Amina
    et al.
    International Agency for Research on Cancer (IARC/WHO), Nutrition and Metabolism Branch, Lyon, France; Department of Prevention Cancer Environment, Centre Léon Bérard, Lyon, France.
    Freisling, Heinz
    International Agency for Research on Cancer (IARC/WHO), Nutrition and Metabolism Branch, Lyon, France.
    Jenab, Mazda
    International Agency for Research on Cancer (IARC/WHO), Nutrition and Metabolism Branch, Lyon, France.
    Tsilidis, Konstantinos K.
    Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece; Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom.
    Trichopoulou, Antonia
    Hellenic Health Foundation, Athens, Greece.
    Boffetta, Paolo
    Stony Brook Cancer Center, Stony Brook University, NY, Stony Brook, United States; Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy.
    van Guelpen, Bethany
    Umeå universitet, Medicinska fakulteten, Wallenberg centrum för molekylär medicin vid Umeå universitet (WCMM). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Mokoroa, Olatz
    Public Health Division of Gipuzkoa, BioDonostia Research Institute, San Sebastian, Spain.
    Wilsgaard, Tom
    Department of Community Medicine, UiT The Arctic University of Norway, Tromsø, Norway.
    Kee, Frank
    Institute for Health Sciences Risk and Inequality, Centre for Public Health, Belfast, United Kingdom.
    Schöttker, Ben
    Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.
    Ordóñez-Mena, José M.
    Nuffield Department of Primary Care Health Sciences, Radcliffe Observatory Quarter, Woodstock Road, Oxford, United Kingdom; NIHR Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom.
    Männistö, Satu
    Department of Public Health and Welfare, Finnish Institute for Health and Welfare (THL), Helsinki, Finland.
    Söderberg, Stefan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Vermeulen, Roel C. H.
    Environmental Epidemiology, Institute for Risk Assessment Sciences (IRAS), Utrecht University, Utrecht, Netherlands.
    Quirós, J. Ramón
    Public Health Directorate, Asturias, Spain.
    Liao, Linda M.
    Division of Cancer Epidemiology and Genetics, National Cancer Institute, MD, Bethesda, United States.
    Sinha, Rashmi
    Division of Cancer Epidemiology and Genetics, National Cancer Institute, MD, Bethesda, United States.
    Kuulasmaa, Kari
    Department of Public Health and Welfare, Finnish Institute for Health and Welfare (THL), Helsinki, Finland.
    Brenner, Hermann
    Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany; Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany; German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.
    Romieu, Isabelle
    International Agency for Research on Cancer (IARC/WHO), Nutrition and Metabolism Branch, Lyon, France.
    Prevalent diabetes and risk of total, colorectal, prostate and breast cancers in an ageing population: meta-analysis of individual participant data from cohorts of the CHANCES consortium2021Ingår i: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 124, nr 11, s. 1882-1890Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: We investigated whether associations between prevalent diabetes and cancer risk are pertinent to older adults and whether associations differ across subgroups of age, body weight status or levels of physical activity.

    Methods: We harmonised data from seven prospective cohort studies of older individuals in Europe and the United States participating in the CHANCES consortium. Cox proportional hazard regression was used to estimate the associations of prevalent diabetes with cancer risk (all cancers combined, and for colorectum, prostate and breast). We calculated summary risk estimates across cohorts using pooled analysis and random-effects meta-analysis.

    Results: A total of 667,916 individuals were included with an overall median (P25–P75) age at recruitment of 62.3 (57–67) years. During a median follow-up time of 10.5 years, 114,404 total cancer cases were ascertained. Diabetes was not associated with the risk of all cancers combined (hazard ratio (HR) = 0.94; 95% confidence interval (CI): 0.86–1.04; I2 = 63.3%). Diabetes was positively associated with colorectal cancer risk in men (HR = 1.17; 95% CI: 1.08–1.26; I2 = 0%) and a similar HR in women (1.13; 95% CI: 0.82–1.56; I2 = 46%), but with a confidence interval including the null. Diabetes was inversely associated with prostate cancer risk (HR = 0.81; 95% CI: 0.77–0.85; I2 = 0%), but not with postmenopausal breast cancer (HR = 0.96; 95% CI: 0.89–1.03; I2 = 0%). In exploratory subgroup analyses, diabetes was inversely associated with prostate cancer risk only in men with overweight or obesity.

    Conclusions: Prevalent diabetes was positively associated with colorectal cancer risk and inversely associated with prostate cancer risk in older Europeans and Americans.

  • 8. Archambault, Alexi N.
    et al.
    Su, Yu-Ru
    Jeon, Jihyoun
    Thomas, Minta
    Lin, Yi
    Conti, David V.
    Win, Aung Ko
    Sakoda, Lori C.
    Lansdorp-Vogelaar, Iris
    Peterse, Elisabeth F. P.
    Zauber, Ann G.
    Duggan, David
    Holowatyj, Andreana N.
    Huyghe, Jeroen R.
    Brenner, Hermann
    Cotterchio, Michelle
    Bézieau, Stéphane
    Schmit, Stephanie L.
    Edlund, Christopher K.
    Southey, Melissa C.
    MacInnis, Robert J.
    Campbell, Peter T.
    Chang-Claude, Jenny
    Slattery, Martha L.
    Chan, Andrew T.
    Joshi, Amit D.
    Song, Mingyang
    Cao, Yin
    Woods, Michael O.
    White, Emily
    Weinstein, Stephanie J.
    Ulrich, Cornelia M.
    Hoffmeister, Michael
    Bien, Stephanie A.
    Harrison, Tabitha A.
    Hampe, Jochen
    Li, Christopher I.
    Schafmayer, Clemens
    Offit, Kenneth
    Pharoah, Paul D.
    Moreno, Victor
    Lindblom, Annika
    Wolk, Alicja
    Wu, Anna H.
    Li, Li
    Gunter, Marc J.
    Gsur, Andrea
    Keku, Temitope O.
    Pearlman, Rachel
    Bishop, D. Timothy
    Castellví-Bel, Sergi
    Moreira, Leticia
    Vodicka, Pavel
    Kampman, Ellen
    Giles, Graham G.
    Albanes, Demetrius
    Baron, John A.
    Berndt, Sonja I.
    Brezina, Stefanie
    Buch, Stephan
    Buchanan, Daniel D.
    Trichopoulou, Antonia
    Severi, Gianluca
    Chirlaque, María-Dolores
    Sánchez, Maria-José
    Palli, Domenico
    Kühn, Tilman
    Murphy, Neil
    Cross, Amanda J.
    Burnett-Hartman, Andrea N.
    Chanock, Stephen J.
    de la Chapelle, Albert
    Easton, Douglas F.
    Elliott, Faye
    English, Dallas R.
    Feskens, Edith J. M.
    FitzGerald, Liesel M.
    Goodman, Phyllis J.
    Hopper, John L.
    Hudson, Thomas J.
    Hunter, David J.
    Jacobs, Eric J.
    Joshu, Corinne E.
    Küry, Sébastien
    Markowitz, Sanford D.
    Milne, Roger L.
    Platz, Elizabeth A.
    Rennert, Gad
    Rennert, Hedy S.
    Schumacher, Fredrick R.
    Sandler, Robert S.
    Seminara, Daniela
    Tangen, Catherine M.
    Thibodeau, Stephen N.
    Toland, Amanda E.
    van Duijnhoven, Franzel J. B.
    Visvanathan, Kala
    Vodickova, Ludmila
    Potter, John D.
    Männistö, Satu
    Weigl, Korbinian
    Figueiredo, Jane
    Martín, Vicente
    Larsson, Susanna C.
    Parfrey, Patrick S.
    Huang, Wen-Yi
    Lenz, Heinz-Josef
    Castelao, Jose E.
    Gago-Dominguez, Manuela
    Muñoz-Garzón, Victor
    Mancao, Christoph
    Haiman, Christopher A.
    Wilkens, Lynne R.
    Siegel, Erin
    Barry, Elizabeth
    Younghusband, Ban
    van Guelpen, Bethany
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi. Umeå universitet, Medicinska fakulteten, Wallenberg centrum för molekylär medicin vid Umeå universitet (WCMM).
    Harlid, Sophia
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Zeleniuch-Jacquotte, Anne
    Liang, Peter S.
    Du, Mengmeng
    Casey, Graham
    Lindor, Noralane M.
    Le Marchand, Loic
    Gallinger, Steven J.
    Jenkins, Mark A.
    Newcomb, Polly A.
    Gruber, Stephen B.
    Schoen, Robert E.
    Hampel, Heather
    Corley, Douglas A.
    Hsu, Li
    Peters, Ulrike
    Hayes, Richard B.
    Cumulative Burden of Colorectal Cancer-Associated Genetic Variants Is More Strongly Associated With Early-Onset vs Late-Onset Cancer2020Ingår i: Gastroenterology, ISSN 0016-5085, E-ISSN 1528-0012, Vol. 158, nr 5, s. 1274-1286.e12Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND & AIMS: Early-onset colorectal cancer (CRC, in persons younger than 50 years old) is increasing in incidence; yet, in the absence of a family history of CRC, this population lacks harmonized recommendations for prevention. We aimed to determine whether a polygenic risk score (PRS) developed from 95 CRC-associated common genetic risk variants was associated with risk for early-onset CRC.

    METHODS: We studied risk for CRC associated with a weighted PRS in 12,197 participants younger than 50 years old vs 95,865 participants 50 years or older. PRS was calculated based on single nucleotide polymorphisms associated with CRC in a large-scale genome-wide association study as of January 2019. Participants were pooled from 3 large consortia that provided clinical and genotyping data: the Colon Cancer Family Registry, the Colorectal Transdisciplinary Study, and the Genetics and Epidemiology of Colorectal Cancer Consortium and were all of genetically defined European descent. Findings were replicated in an independent cohort of 72,573 participants.

    RESULTS: Overall associations with CRC per standard deviation of PRS were significant for early-onset cancer, and were stronger compared with late-onset cancer (P for interaction = .01); when we compared the highest PRS quartile with the lowest, risk increased 3.7-fold for early-onset CRC (95% CI 3.28-4.24) vs 2.9-fold for late-onset CRC (95% CI 2.80-3.04). This association was strongest for participants without a first-degree family history of CRC (P for interaction = 5.61 × 10-5). When we compared the highest with the lowest quartiles in this group, risk increased 4.3-fold for early-onset CRC (95% CI 3.61-5.01) vs 2.9-fold for late-onset CRC (95% CI 2.70-3.00). Sensitivity analyses were consistent with these findings.

    CONCLUSIONS: In an analysis of associations with CRC per standard deviation of PRS, we found the cumulative burden of CRC-associated common genetic variants to associate with early-onset cancer, and to be more strongly associated with early-onset than late-onset cancer, particularly in the absence of CRC family history. Analyses of PRS, along with environmental and lifestyle risk factors, might identify younger individuals who would benefit from preventive measures.

  • 9.
    Baker, Jacqueline Roshelli
    et al.
    Department of Epidemiology, Rollins School of Public Health, Emory University, GA, Atlanta, United States.
    Umesh, Sushma
    Department of Epidemiology, Rollins School of Public Health, Emory University, GA, Atlanta, United States.
    Jenab, Mazda
    International Agency for Research on Cancer, Lyon, France.
    Schomburg, Lutz
    Institut für Experimentelle Endokrinologie, Charité Universitätsmedizin Berlin, Berlin, Germany.
    Tjønneland, Anne
    Danish Cancer Society Research Center, Diet, Genes and Environment, Copenhagen, Denmark.
    Olsen, Anja
    Danish Cancer Society Research Center, Diet, Genes and Environment, Copenhagen, Denmark.
    Boutron-Ruault, Marie-Christine
    CESP (UMR1018), Faculté de Médecine, Université Paris-Saclay, Inserm, Gustave Roussy, Villejuif, France.
    Rothwell, Joseph A.
    CESP (UMR1018), Faculté de Médecine, Université Paris-Saclay, Inserm, Gustave Roussy, Villejuif, France.
    Severi, Gianluca
    CESP (UMR1018), Faculté de Médecine, Université Paris-Saclay, Inserm, Gustave Roussy, Villejuif, France; Department of Statistics, Computer Science and Applications (DISIA), University of Florence, Florence, Italy.
    Katzke, Verena
    Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
    Johnson, Theron
    Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
    Schulze, Matthias B.
    Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany; Institute of Nutrition Science, University of Potsdam, Nuthetal, Germany.
    Masala, Giovanna
    Cancer Risk Factors and Lifestyle Epidemiology Unit, Institute for Cancer Research, Prevention and Clinical Network-ISPRO, Florence, Italy.
    Agnoli, Claudia
    Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy.
    Simeon, Vittorio
    Dipartimento di Salute Mentale e Fisica e Medicina Preventiva, Università degli Studi della Campania ‘Luigi Vanvitelli’, Naples, Italy.
    Tumino, Rosario
    Cancer Registry and Histopathology Department, Provincial Health Authority (ASP 7), Ragusa, Italy.
    Bueno-De-mesquita, H. Bas
    Center for Nutrition and Health, National Institute for Public Health and the Environment, Bilthoven, Netherlands.
    Gram, Inger Torhild
    Department of Community Medicine, The Arctic University of Norway, Tromsø, Norway.
    Skeie, Guri
    Department of Community Medicine, The Arctic University of Norway, Tromsø, Norway.
    Bonet, Catalina
    Unitat de Nutrició i Càncer, Malaga, Spain.
    Rodriguez-Barranco, Miguel
    Escuela Andaluza de Salud Pública (EASP), Instituto de Investigación Biosanitaria ibs. Granada, Granada, Spain; Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain.
    Houerta, José María
    Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain; Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca, Murcia, Spain.
    Gylling, Björn
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Van Guelpen, Bethany
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Perez-Cornago, Aurora
    Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.
    Aglago, Elom
    International Agency for Research on Cancer, Lyon, France.
    Freisling, Heinz
    International Agency for Research on Cancer, Lyon, France.
    Weiderpass, Elisabete
    International Agency for Research on Cancer, Lyon, France.
    Cross, Amanda J.
    School of Public Health, Imperial College London, London, United Kingdom.
    Heath, Alicia K.
    School of Public Health, Imperial College London, London, United Kingdom.
    Hughes, David J.
    Cancer Biology and Therapeutics Group, School of Biomolecular and Biomedical Science, UCD Conway Institute, University College Dublin, Dublin, Ireland.
    Fedirko, Veronika
    Department of Epidemiology, Rollins School of Public Health, Emory University, GA, Atlanta, United States; Department of Epidemiology, The University of Texas MD Anderson Cancer Center, TX, Houston, United States.
    Prediagnostic blood selenium status and mortality among patients with colorectal cancer in western european populations2021Ingår i: Biomedicines, E-ISSN 2227-9059, Vol. 9, nr 11, artikel-id 1521Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    A higher selenium (Se) status has been shown to be associated with lower risk for colorectal cancer (CRC), but the importance of Se in survival after CRC diagnosis is not well studied. The associations of prediagnostic circulating Se status (as indicated by serum Se and selenoprotein P (SELENOP) measurements) with overall and CRC-specific mortality were estimated using multi-variable Cox proportional hazards regression among 995 CRC cases (515 deaths, 396 from CRC) in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Se and SELENOP serum concentrations were measured on average 46 months before CRC diagnosis. Median follow-up time was 113 months. Participants with Se concentrations in the highest quintile (≥100 µg/L) had a multivariable-adjusted hazard ratio (HR) of 0.73 (95% CI: 0.52–1.02; Ptrend = 0.06) for CRC-specific mortality and 0.77 (95% CI: 0.57–1.03; Ptrend = 0.04) for overall mortality, compared with the lowest quintile (≤67.5 µg/L). Similarly, participants with SELENOP concentrations in the highest (≥5.07 mg/L) compared with the lowest quintile (≤3.53 mg/L) had HRs of 0.89 (95% CI: 0.64–1.24; Ptrend = 0.39) for CRC-specific mortality and 0.83 (95% CI: 0.62–1.11; Ptrend = 0.17) for overall mortal-ity. Higher prediagnostic exposure to Se within an optimal concentration (100–150 µg/L) might be associated with improved survival among CRC patients, although our results were not statistically significant and additional studies are needed to confirm this potential association. Our findings may stimulate further research on selenium’s role in survival among CRC patients especially among those residing in geographic regions with suboptimal Se availability.

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  • 10. Benetou, Vassiliki
    et al.
    Orfanos, Philippos
    Benetos, Ioannis S
    Pala, Valeria
    Evangelista, Alberto
    Frasca, Graziella
    Giurdanella, Maria Concetta
    Peeters, Petra HM
    van der Schouw, Yvonne T
    Rohrmann, Sabine
    Linseisen, Jakob
    Boeing, Heiner
    Weikert, Cornelia
    Pettersson, Ulrika
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk farmakologi.
    Van Guelpen, Bethany
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Bueno-de-Mesquita, H Bas
    Altzibar, Jone
    Boffetta, Paolo
    Trichopoulou, Antonia
    Anthropometry, physical activity and hip fractures in the elderly2011Ingår i: Injury, ISSN 0020-1383, E-ISSN 1879-0267, Vol. 42, nr 2, s. 188-193Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    INTRODUCTION: Hip fractures constitute a major and growing public health problem amongst the elderly worldwide. We examined the association of anthropometry and physical activity with hip fracture incidence in a cohort of elderly Europeans, participants in the European Prospective Investigation into Cancer and nutrition (EPIC) study.

    MATERIALS AND METHODS: The study population consisted of 27982 volunteers (10553 men and 17429 women) aged 60 years and above from five European countries. Information on anthropometry, physical activity, medical history and other characteristics was collected at baseline. During a median follow-up of 8 years, 261 incident hip fractures (203 women and 58 men) were recorded. Data were analysed through Cox proportional hazard regression with adjustment for potential confounders.

    RESULTS: A higher body mass index (BMI) was associated with lower hip fracture risk (hazard ratio (HR) per increasing sex-specific-quintile: 0.85, 95% confidence interval (95% CI): 0.77-0.94). Body height was associated with increased hip fracture risk (HR per 5cm: 1.13, 95% CI: 1.01-1.25). Waist-to-hip ratio was not related to hip fracture risk. Increasing levels of leisure-time physical activity were related to lower risk (HR per increasing tertile: 0.84, 95% CI: 0.70-0.99, p for trend: 0.039).

    CONCLUSIONS: In a prospective cohort study of elderly Europeans, we found evidence that high body stature increased and high BMI decreased the incidence of hip fractures. After adjustment for BMI, waist-to-hip ratio was not associated with hip fracture risk. Leisure-time physical activity appears to play a beneficial role in the prevention of hip fractures.

  • 11. Bien, Stephanie A.
    et al.
    Su, Yu-Ru
    Conti, David V.
    Harrison, Tabitha A.
    Qu, Conghui
    Guo, Xingyi
    Lu, Yingchang
    Albanes, Demetrius
    Auer, Paul L.
    Banbury, Barbara L.
    Berndt, Sonja I.
    Bezieau, Stephane
    Brenner, Hermann
    Buchanan, Daniel D.
    Caan, Bette J.
    Campbell, Peter T.
    Carlson, Christopher S.
    Chan, Andrew T.
    Chang-Claude, Jenny
    Chen, Sai
    Connolly, Charles M.
    Easton, Douglas F.
    Feskens, Edith J. M.
    Gallinger, Steven
    Giles, Graham G.
    Gunter, Marc J.
    Hampe, Jochen
    Huyghe, Jeroen R.
    Hoffmeister, Michael
    Hudson, Thomas J.
    Jacobs, Eric J.
    Jenkins, Mark A.
    Kampman, Ellen
    Kang, Hyun Min
    Kuehn, Tilman
    Kury, Sebastien
    Lejbkowicz, Flavio
    Le Marchand, Loic
    Milne, Roger L.
    Li, Li
    Li, Christopher I.
    Lindblom, Annika
    Lindor, Noralane M.
    Martin, Vicente
    McNeil, Caroline E.
    Melas, Marilena
    Moreno, Victor
    Newcomb, Polly A.
    Offit, Kenneth
    Pharaoh, Paul D. P.
    Potter, John D.
    Qu, Chenxu
    Riboli, Elio
    Rennert, Gad
    Sala, Nuria
    Schafmayer, Clemens
    Scacheri, Peter C.
    Schmit, Stephanie L.
    Severi, Gianluca
    Slattery, Martha L.
    Smith, Joshua D.
    Trichopoulou, Antonia
    Tumino, Rosario
    Ulrich, Cornelia M.
    van Duijnhoven, Franzel J. B.
    van Guelpen, Bethany
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi. Department of Public Health Sciences, University of Virginia School of Medicine, Charlottesville, USA.
    Weinstein, Stephanie J.
    White, Emily
    Wolk, Alicja
    Woods, Michael O.
    Wu, Anna H.
    Abecasis, Goncalo R.
    Casey, Graham
    Nickerson, Deborah A.
    Gruber, Stephen B.
    Hsu, Li
    Zheng, Wei
    Peters, Ulrike
    Genetic variant predictors of gene expression provide new insight into risk of colorectal cancer2019Ingår i: Human Genetics, ISSN 0340-6717, E-ISSN 1432-1203, Vol. 138, nr 4, s. 307-326Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Genome-wide association studies have reported 56 independently associated colorectal cancer (CRC) risk variants, most of which are non-coding and believed to exert their effects by modulating gene expression. The computational method PrediXcan uses cis-regulatory variant predictors to impute expression and perform gene-level association tests in GWAS without directly measured transcriptomes. In this study, we used reference datasets from colon (n=169) and whole blood (n=922) transcriptomes to test CRC association with genetically determined expression levels in a genome-wide analysis of 12,186 cases and 14,718 controls. Three novel associations were discovered from colon transverse models at FDR0.2 and further evaluated in an independent replication including 32,825 cases and 39,933 controls. After adjusting for multiple comparisons, we found statistically significant associations using colon transcriptome models with TRIM4 (discovery P=2.2x10(-4), replication P=0.01), and PYGL (discovery P=2.3x10(-4), replication P=6.7x10(-4)). Interestingly, both genes encode proteins that influence redox homeostasis and are related to cellular metabolic reprogramming in tumors, implicating a novel CRC pathway linked to cell growth and proliferation. Defining CRC risk regions as one megabase up- and downstream of one of the 56 independent risk variants, we defined 44 non-overlapping CRC-risk regions. Among these risk regions, we identified genes associated with CRC (P<0.05) in 34/44 CRC-risk regions. Importantly, CRC association was found for two genes in the previously reported 2q25 locus, CXCR1 and CXCR2, which are potential cancer therapeutic targets. These findings provide strong candidate genes to prioritize for subsequent laboratory follow-up of GWAS loci. This study is the first to implement PrediXcan in a large colorectal cancer study and findings highlight the utility of integrating transcriptome data in GWAS for discovery of, and biological insight into, risk loci.

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  • 12.
    Bodén, Stina
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Harbs, Justin
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Sundkvist, Anneli
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Fuchs, Klara
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Myte, Robin
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Gylling, Björn
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Zingmark, Carl
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Löfgren Burström, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Palmqvist, Richard
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Harlid, Sophia
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    van Guelpen, Bethany
    Umeå universitet, Medicinska fakulteten, Wallenberg centrum för molekylär medicin vid Umeå universitet (WCMM). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Plasma concentrations of gut hormones acyl ghrelin and peptide YY and subsequent risk of colorectal cancer and molecular tumor subtypes2023Ingår i: Cancer Prevention Research, ISSN 1940-6207, E-ISSN 1940-6215, Vol. 16, nr 2, s. 75-87Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Obesity and metabolic dysfunction are implicated in colorectal cancer development. Appetite-regulating gut hormones might have a role in colorectal cancer risk. We investigated whether circulating levels of the gut hormones ghrelin (analyzed as acyl ghrelin) and Peptide YY (PYY) were associated with subsequent colorectal cancer risk, including clinical and molecular tumor subtypes. We also provide descriptive data on these hormones in relation to background participant characteristics and metabolic biomarkers. This population-based study included 1,010 matched case-control pairs with a median of 12.3 years of follow-up. Acyl ghrelin and PYY were measured by multiplex immunoassay. Data on KRAS and BRAF mutations and microsatellite instability (MSI) status were available for 704 and 708 cases, respectively. Conditional logistic regression models estimated association to colorectal cancer risk. Partial correlation and linear regression were used to investigate relationships between background and metabolic variables and variation in plasma gut hormone concentrations. Acyl ghrelin was not clearly associated with colorectal cancer risk (multivariable OR per 1 SD increase: 1.11; 95% CI, 1.00-1.23). Positive associations were observed for specific subtypes, in particular BRAF-mutated colorectal cancer and right-sided colon cancer, although with nonsignificant heterogeneity. PYY was not related to colorectal cancer risk (multivariable OR per 1 SD: 1.04; 95% CI, 0.95-1.14) or any tumor subtype. In the control participants, ghrelin was inversely correlated with BMI, and PYY was positively correlated with C-peptide and insulin levels. These findings provide limited support for a possible role for ghrelin in colorectal cancer development, primarily in specific anatomical and molecular tumor subtypes.

    PREVENTION RELEVANCE: The findings of this study do not support a major role for the metabolic gut hormones ghrelin and PYY in colorectal cancer development but suggest the possibility of an involvement for ghrelin in specific tumor subtypes. Elucidating subtype-specific risk factors and mechanisms of carcinogenesis may have implications for precision prevention.

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  • 13.
    Bodén, Stina
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Myte, Robin
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Harbs, Justin
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Sundkvist, Anneli
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Zingmark, Carl
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Löfgren Burström, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Palmqvist, Richard
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Harlid, Sophia
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    van Guelpen, Bethany
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi. Umeå universitet, Medicinska fakulteten, Wallenberg centrum för molekylär medicin vid Umeå universitet (WCMM).
    C-reactive Protein and Future Risk of Clinical and Molecular Subtypes of Colorectal Cancer2020Ingår i: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 29, nr 7, s. 1482-1491Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Inflammation has been implicated in colorectal cancer etiology, but the relationship between C-reactive protein (CRP) and colorectal cancer risk is unclear. We aimed to investigate the association between prediagnostic plasma CRP concentrations and the risk of clinical and molecular colorectal cancer subtypes.

    Methods: We used prospectively collected samples from 1,010 matched colorectal cancer case-control pairs from two population-based cohorts in Northern Sweden, including 259 with repeated samples. Conditional logistic regression and linear mixed models were used to estimate relative risks of colorectal cancer, including subtypes based on BRAF and KRAS mutations, microsatellite instability status, tumor location, stage, lag time, and (using unconditional logistic regression) body mass index.

    Results: CRP was not associated with colorectal cancer risk, regardless of clinical or molecular colorectal cancer subtype. For participants with advanced tumors and blood samples <5 years before diagnosis, CRP was associated with higher risk [OR per 1 unit increase in natural logarithm (In) transformed CRP, 1.32; 95% confidence interval (CI), 1.01-1.73]. CRP levels increased over time, but average time trajectories were similar for cases and controls (P-interaction = 0.19).

    Conclusions: Our results do not support intertumoral heterogeneity as an explanation for previous inconsistent findings regarding the role of CRP in colorectal cancer etiology. The possible association in the subgroup with advanced tumors and shorter follow-up likely reflects undiagnosed cancer at baseline. Impact: Future efforts to establish the putative role of chronic, low-grade inflammation in colorectal cancer development will need to address the complex relationship between systemic inflammatory factors and tumor microenvironment, and might consider larger biomarker panels than CRP alone.

  • 14.
    Bodén, Stina
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Myte, Robin
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Wennberg, Maria
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning. Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för hållbar hälsa.
    Harlid, Sophia
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Johansson, Ingegerd
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi, Tandläkarutbildning. Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för hållbar hälsa.
    Shivappa, Nitin
    Hébert, James R
    van Guelpen, Bethany
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi. Umeå universitet, Medicinska fakulteten, Wallenberg centrum för molekylär medicin vid Umeå universitet (WCMM).
    Nilsson, Lena Maria
    Umeå universitet, Arktiskt centrum vid Umeå universitet (Arcum). Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning. Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för hållbar hälsa.
    The inflammatory potential of diet in determining cancer risk: a prospective investigation of two dietary pattern scores2019Ingår i: PLOS ONE, E-ISSN 1932-6203, Vol. 14, nr 4, artikel-id e0214551Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    PURPOSE: Inflammation-related mechanisms may contribute to the link between diet and cancer. We sought to investigate the inflammatory impact of diet on cancer risk using the Dietary inflammatory index (DII) and an adapted Mediterranean diet score (MDS).

    METHODS: This population-based, prospective cohort study used self-reported dietary data from the Västerbotten Intervention Programme, including 100,881 participants, of whom 35,393 had repeated measures. Associations between dietary patterns and cancer risk were evaluated using Cox proportional hazards regression. We also used restricted cubic splines to test for potential non-linear associations.

    RESULTS: A total of 9,250 incident cancer cases were diagnosed during a median follow-up of 15 years. The two dietary patterns were moderately correlated to each other and had similar associations with cancer risk, predominantly lung cancer in men (DII per tertile decrease: Hazard ratio (HR) 0.81 (0.66-0.99), MDS per tertile increase: HR 0.86 (0.72-1.03)), and gastric cancer in men (DII: 0.73 (0.53-0.99), MDS: 0.73 (0.56-0.96)). Associations were, in general, found to be linear. We found no longitudinal association between 10-year change in diet and cancer risk.

    CONCLUSION: We confirm small, but consistent and statistically significant associations between a more anti-inflammatory or healthier diet and reduced risk of cancer, including a lower risk of lung and gastric cancer in men. The dietary indexes produced similar associations with respect to the risk of cancer.

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  • 15.
    Bodén, Stina
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Wennberg, Maria
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Van Guelpen, Bethany
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Johansson, Ingegerd
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Lindahl, Bernt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Andersson, Jonas
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Shivappa, Nitin
    Hebert, James R
    Nilsson, Lena Maria
    Umeå universitet, Arktiskt centrum vid Umeå universitet (Arcum). Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Dietary inflammatory index and risk of first myocardial infarction: a prospective population-based study2017Ingår i: Nutrition Journal, ISSN 1475-2891, E-ISSN 1475-2891, Vol. 16, artikel-id 21Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Chronic, low-grade inflammation is an established risk factor for cardiovascular disease. The inflammatory impact of diet can be reflected by concentrations of inflammatory markers in the bloodstream and the inflammatory potential of diet can be estimated by the dietary inflammatory index (DII(TM)), which has been associated with cardiovascular disease risk in some previous studies. We aimed to examine the association between the DII and the risk of first myocardial infarction (MI) in a population-based study with long follow-up.

    METHOD: We conducted a prospective case-control study of 1389 verified cases of first MI and 5555 matched controls nested within the population-based cohorts of the Northern Sweden Health and Disease Study (NSHDS), of which the largest is the ongoing Västerbotten Intervention Programme (VIP) with nearly 100 000 participants during the study period. Median follow-up from recruitment to MI diagnosis was 6.4 years (6.2 for men and 7.2 for women). DII scores were derived from a validated food frequency questionnaire (FFQ) administered in 1986-2006. Multivariable conditional logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals (CI), using quartile 1 (most anti-inflammatory diet) as the reference category. For validation, general linear models were used to estimate the association between the DII scores and two inflammatory markers, high-sensitivity C-reactive protein (hsCRP) and interleukin 6 (IL-6) in a subset (n = 605) of the study population.

    RESULTS: Male participants with the most pro-inflammatory DII scores had an increased risk of MI [ORQ4vsQ1 = 1.57 (95% CI 1.21-2.02) P trend = 0.02], which was essentially unchanged after adjustment for potential confounders, including cardiovascular risk factors [ORQ4vsQ1 = 1.50 (95% CI 1.14-1.99), P trend = 0.10]. No association was found between DII and MI in women. An increase of one DII score unit was associated with 9% higher hsCRP (95% CI 0.03-0.14) and 6% higher IL-6 (95% CI 0.02-0.11) in 605 controls with biomarker data available.

    CONCLUSION: A pro-inflammatory diet was associated with an elevated risk of first myocardial infarction in men; whereas for women the relationship was null. Consideration of the inflammatory impact of diet could improve prevention of cardiovascular disease.

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  • 16.
    Bodén, Stina
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Zheng, Rui
    Hanhineva, Kati
    Landberg, Rikard
    Harlid, Sophia
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Vidman, Linda
    Gunter, Marc
    Winkvist, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för hållbar hälsa. Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Sweden.
    Johansson, Ingegerd
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi. Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning. Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    van Guelpen, Bethany
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi. Umeå universitet, Medicinska fakulteten, Wallenberg centrum för molekylär medicin vid Umeå universitet (WCMM).
    Brunius, Carl
    Data-driven dietary patterns and their association with colorectal cancer risk and untargeted plasma metabolite profilesManuskript (preprint) (Övrigt vetenskapligt)
  • 17.
    Bodén, Stina
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi. Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Zheng, Rui
    Department of Surgical Sciences, The EpiHub, Uppsala University, Uppsala, Sweden.
    Ribbenstedt, Anton
    Department of Life Sciences, Chalmers University of Technology, Gothenburg, Sweden.
    Landberg, Rikard
    Department of Life Sciences, Chalmers University of Technology, Gothenburg, Sweden.
    Harlid, Sophia
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Vidman, Linda
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Gunter, Marc J.
    International Agency for Research On Cancer, Nutrition and Metabolism Section, Lyon Cedex 08, France; Cancer Epidemiology and Prevention Research Unit, Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom.
    Winkvist, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för hållbar hälsa. Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Johansson, Ingegerd
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    van Guelpen, Bethany
    Umeå universitet, Medicinska fakulteten, Wallenberg centrum för molekylär medicin vid Umeå universitet (WCMM). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Brunius, Carl
    Department of Life Sciences, Chalmers University of Technology, Gothenburg, Sweden.
    Dietary patterns, untargeted metabolite profiles and their association with colorectal cancer risk2024Ingår i: Scientific Reports, E-ISSN 2045-2322, Vol. 14, nr 1, artikel-id 2244Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    We investigated data-driven and hypothesis-driven dietary patterns and their association to plasma metabolite profiles and subsequent colorectal cancer (CRC) risk in 680 CRC cases and individually matched controls. Dietary patterns were identified from combined exploratory/confirmatory factor analysis. We assessed association to LC–MS metabolic profiles by random forest regression and to CRC risk by multivariable conditional logistic regression. Principal component analysis was used on metabolite features selected to reflect dietary exposures. Component scores were associated to CRC risk and dietary exposures using partial Spearman correlation. We identified 12 data-driven dietary patterns, of which a breakfast food pattern showed an inverse association with CRC risk (OR per standard deviation increase 0.89, 95% CI 0.80–1.00, p = 0.04). This pattern was also inversely associated with risk of distal colon cancer (0.75, 0.61–0.96, p = 0.01) and was more pronounced in women (0.69, 0.49–0.96, p = 0.03). Associations between meat, fast-food, fruit soup/rice patterns and CRC risk were modified by tumor location in women. Alcohol as well as fruit and vegetables associated with metabolite profiles (Q2 0.22 and 0.26, respectively). One metabolite reflecting alcohol intake associated with increased CRC risk, whereas three metabolites reflecting fiber, wholegrain, and fruit and vegetables associated with decreased CRC risk.

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  • 18.
    Bouras, Emmanouil
    et al.
    Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece.
    Kim, Andre E.
    Division of Biostatistics, Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, CA, Los Angeles, United States.
    Lin, Yi
    Public Health Sciences Division, Fred Hutchinson Cancer Center, WA, Seattle, United States.
    Morrison, John
    Division of Biostatistics, Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, CA, Los Angeles, United States.
    Du, Mengmeng
    Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, NY, New York, United States.
    Albanes, Demetrius
    Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, MD, Bethesda, United States.
    Barry, Elizabeth L.
    Department of Epidemiology, Geisel School of Medicine at Dartmouth, NH, Hanover, United States.
    Baurley, James W.
    Bioinformatics and Data Science Research Center, Bina Nusantara University, Jakarta, Indonesia; BioRealm LLC, CA, Walnut, United States.
    Berndt, Sonja I.
    Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, MD, Bethesda, United States.
    Bien, Stephanie A.
    Public Health Sciences Division, Fred Hutchinson Cancer Center, WA, Seattle, United States.
    Bishop, Timothy D.
    Leeds Institute of Cancer and Pathology, University of Leeds, Leeds, United Kingdom.
    Brenner, Hermann
    Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany; Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany; German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.
    Budiarto, Arif
    Bioinformatics and Data Science Research Center, Bina Nusantara University, Jakarta, Indonesia; Computer Science Department, School of Computer Science, Bina Nusantara University, Jakarta, Indonesia.
    Burnett-Hartman, Andrea
    Institute for Health Research, Kaiser Permanente Colorado, CO, Denver, United States.
    Campbell, Peter T.
    Department of Epidemiology and Population Health, Albert Einstein College of Medicine, NY, Bronx, United States.
    Carreras-Torres, Robert
    Unit of Biomarkers and Suceptibility (UBS), Oncology Data Analytics Program (ODAP), Catalan Institute of Oncology (ICO), L'Hospitalet del Llobregat, Barcelona, Spain; ONCOBELL Program, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain; Digestive Diseases and Microbiota Group, Girona Biomedical Research Institute (IDIBGI), Salt, Girona, Spain.
    Casey, Graham
    Center for Public Health Genomics, University of Virginia, VA, Charlottesville, United States.
    Cenggoro, Tjeng Wawan
    Bioinformatics and Data Science Research Center, Bina Nusantara University, Jakarta, Indonesia; Computer Science Department, School of Computer Science, Bina Nusantara University, Jakarta, Indonesia.
    Chan, Andrew T.
    Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, MA, Boston, United States; Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, MA, Boston, United States; Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, MA, Boston, United States; Broad Institute of Harvard and MIT, MA, Cambridge, United States; Department of Epidemiology, Harvard TH Chan School of Public Health, Harvard University, MA, Boston, United States; Department of Immunology and Infectious Diseases, Harvard TH Chan School of Public Health, Harvard University, MA, Boston, United States.
    Chang-Claude, Jenny
    Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany; University Medical Centre Hamburg-Eppendorf, University Cancer Centre Hamburg (UCCH), Hamburg, Germany.
    Conti, David V.
    Division of Biostatistics, Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, CA, Los Angeles, United States.
    Cotterchio, Michelle
    Ontario Health (Cancer Care Ontario), ON, Toronto, Canada.
    Devall, Matthew
    Center for Public Health Genomics, Department of Public Health Sciences, University of Virginia, VA, Charlottesville, United States; Department of Public Health Sciences, Center for Public Health Genomics, VA, Charlottesville, United States.
    Diez-Obrero, Virginia
    Unit of Biomarkers and Suceptibility (UBS), Oncology Data Analytics Program (ODAP), Catalan Institute of Oncology (ICO), L'Hospitalet del Llobregat, Barcelona, Spain; ONCOBELL Program, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain.
    Dimou, Niki
    Nutrition and Metabolism Branch, International Agency for Research on Cancer, Lyon, France.
    Drew, David A.
    Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, MA, Boston, United States.
    Figueiredo, Jane C.
    Department of Medicine, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, CA, Los Angeles, United States.
    Giles, Graham G.
    Cancer Epidemiology Division, Cancer Council Victoria, VIC, Melbourne, Australia; Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, VIC, Melbourne, Australia; Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, VIC, Clayton, Australia.
    Gruber, Stephen B.
    Department of Medical Oncology & Therapeutics Research, City of Hope National Medical Center, CA, Duarte, United States.
    Gunter, Marc J.
    Nutrition and Metabolism Branch, International Agency for Research on Cancer, Lyon, France.
    Harrison, Tabitha A.
    Public Health Sciences Division, Fred Hutchinson Cancer Center, WA, Seattle, United States.
    Hidaka, Akihisa
    Public Health Sciences Division, Fred Hutchinson Cancer Center, WA, Seattle, United States.
    Hoffmeister, Michael
    Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.
    Huyghe, Jeroen R.
    Public Health Sciences Division, Fred Hutchinson Cancer Center, WA, Seattle, United States.
    Joshi, Amit D.
    Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, MA, Boston, United States; Department of Epidemiology, Harvard TH Chan School of Public Health, Harvard University, MA, Boston, United States.
    Kawaguchi, Eric S.
    Division of Biostatistics, Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, CA, Los Angeles, United States; Department of Biostatistics, Fielding School of Public Health, University of California, Los Angeles, CA, Los Angeles, United States.
    Keku, Temitope O.
    Center for Gastrointestinal Biology and Disease, University of North Carolina, NC, Chapel Hill, United States.
    Kundaje, Anshul
    Department of Genetics, Stanford University, CA, Stanford, United States; Department of Computer Science, Stanford University, CA, Stanford, United States.
    Le Marchand, Loic
    University of Hawaii Cancer Center, HI, Honolulu, United States.
    Lewinger, Juan Pablo
    Division of Biostatistics, Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, CA, Los Angeles, United States.
    Li, Li
    Department of Family Medicine, University of Virginia, VA, Charlottesville, United States.
    Lynch, Brigid M.
    Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, VIC, Melbourne, Australia; Cancer Epidemiology Division, Cancer Council Victoria, VIC, Melbourne, Australia.
    Mahesworo, Bharuno
    Bioinformatics and Data Science Research Center, Bina Nusantara University, Jakarta, Indonesia.
    Männistö, Satu
    Department of Public Health Solutions, National Institute for Health and Welfare, Helsinki, Finland.
    Moreno, Victor
    Unit of Biomarkers and Suceptibility (UBS), Oncology Data Analytics Program (ODAP), Catalan Institute of Oncology (ICO), L'Hospitalet del Llobregat, Barcelona, Spain; ONCOBELL Program, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain; Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), Madrid, Spain; Department of Clinical Sciences, Faculty of Medicine and health Sciences and Universitat de Barcelona Institute of Complex Systems (UBICS), University of Barcelona (UB), L'Hospitalet de Llobregat, Barcelona, Spain.
    Murphy, Neil
    Nutrition and Metabolism Branch, International Agency for Research on Cancer, Lyon, France.
    Newcomb, Polly A.
    Public Health Sciences Division, Fred Hutchinson Cancer Center, WA, Seattle, United States; School of Public Health, University of Washington, WA, Seattle, United States.
    Obón-Santacana, Mireia
    Unit of Biomarkers and Suceptibility (UBS), Oncology Data Analytics Program (ODAP), Catalan Institute of Oncology (ICO), L'Hospitalet del Llobregat, Barcelona, Spain; ONCOBELL Program, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain; Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), Madrid, Spain.
    Ose, Jennifer
    Huntsman Cancer Institute, University of Utah, Utah, Salt Lake City, United States; Department of Population Health Sciences, University of Utah, UT, Salt Lake City, United States.
    Palmer, Julie R.
    Slone Epidemiology Center at Boston University, MA, Boston, United States.
    Papadimitriou, Nikos
    Nutrition and Metabolism Branch, International Agency for Research on Cancer, Lyon, France.
    Pardamean, Bens
    Bioinformatics and Data Science Research Center, Bina Nusantara University, Jakarta, Indonesia.
    Pellatt, Andrew J.
    Department of Cancer Medicine, MD Anderson Cancer Center, TX, Houston, United States.
    Peoples, Anita R.
    Huntsman Cancer Institute, University of Utah, Utah, Salt Lake City, United States; Department of Population Health Sciences, University of Utah, UT, Salt Lake City, United States.
    Platz, Elizabeth A.
    Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, MD, Baltimore, United States.
    Potter, John D.
    Public Health Sciences Division, Fred Hutchinson Cancer Center, WA, Seattle, United States; Research Centre for Hauora and Health, Massey University, Wellington, New Zealand.
    Qi, Lihong
    Department of Public Health Sciences, University of California Davis, CA, Davis, United States.
    Qu, Conghui
    Public Health Sciences Division, Fred Hutchinson Cancer Center, WA, Seattle, United States.
    Rennert, Gad
    Department of Community Medicine and Epidemiology, Lady Davis Carmel Medical Center, Haifa, Israel; Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel; Clalit National Cancer Control Center, Haifa, Israel.
    Ruiz-Narvaez, Edward
    Department of Nutritional Sciences, University of Michigan School of Public Health, MI, Ann Arbor, United States.
    Sakoda, Lori C.
    Public Health Sciences Division, Fred Hutchinson Cancer Center, WA, Seattle, United States; Division of Research, Kaiser Permanente Northern California, CA, Oakland, United States.
    Schmit, Stephanie L.
    Genomic Medicine Institute, Cleveland Clinic, OH, Cleveland, United States; Population and Cancer Prevention Program, Case Comprehensive Cancer Center, OH, Cleveland, United States.
    Shcherbina, Anna
    Department of Genetics, Stanford University, CA, Stanford, United States; Department of Computer Science, Stanford University, CA, Stanford, United States.
    Stern, Mariana C.
    Department of Population and Public Health Sciences and Norris Comprehensive Cancer Center, Preventive Medicine, Keck School of Medicine, University of Southern California, CA, Los Angeles, United States.
    Su, Yu-Ru
    Public Health Sciences Division, Fred Hutchinson Cancer Center, WA, Seattle, United States.
    Tangen, Catherine M.
    SWOG Statistical Center, Fred Hutchinson Cancer Research Center, WA, Seattle, United States.
    Thomas, Duncan C.
    Division of Biostatistics, Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, CA, Los Angeles, United States.
    Tian, Yu
    Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany; School of Public Health, Capital Medical University, Beijing, China.
    Um, Caroline Y.
    Department of Population Science, American Cancer Society, GA, Atlanta, United States.
    van Duijnhoven, Franzel JB.
    Division of Human Nutrition and Health, Wageningen University & Research, Wageningen, Netherlands.
    van Guelpen, Bethany
    Umeå universitet, Medicinska fakulteten, Wallenberg centrum för molekylär medicin vid Umeå universitet (WCMM). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Visvanathan, Kala
    Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, MD, Baltimore, United States.
    Wang, Jun
    Department of Population and Public Health Sciences and Norris Comprehensive Cancer Center, Preventive Medicine, Keck School of Medicine, University of Southern California, CA, Los Angeles, United States.
    White, Emily
    Public Health Sciences Division, Fred Hutchinson Cancer Center, WA, Seattle, United States; Department of Epidemiology, University of Washington School of Public Health, WA, Seattle, United States.
    Wolk, Alicja
    Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Woods, Michael O.
    Memorial University of Newfoundland, Discipline of Genetics, St John's, Canada.
    Ulrich, Cornelia M.
    Huntsman Cancer Institute, University of Utah, Utah, Salt Lake City, United States; Department of Population Health Sciences, University of Utah, UT, Salt Lake City, United States.
    Hsu, Li
    Public Health Sciences Division, Fred Hutchinson Cancer Center, WA, Seattle, United States; Department of Biostatistics, University of Washington, WA, Seattle, United States.
    Gauderman, W James
    Division of Biostatistics, Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, CA, Los Angeles, United States.
    Peters, Ulrike
    Public Health Sciences Division, Fred Hutchinson Cancer Center, WA, Seattle, United States; Department of Epidemiology, University of Washington, WA, Seattle, United States.
    Tsilidis, Konstantinos K.
    Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece; Department of Epidemiology and Biostatistics, Imperial College London, School of Public Health, London, United Kingdom.
    Genome-wide interaction analysis of folate for colorectal cancer risk2023Ingår i: American Journal of Clinical Nutrition, ISSN 0002-9165, E-ISSN 1938-3207, Vol. 118, nr 5, s. 881-891Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Epidemiological and experimental evidence suggests that higher folate intake is associated with decreased colorectal cancer (CRC) risk; however, the mechanisms underlying this relationship are not fully understood. Genetic variation that may have a direct or indirect impact on folate metabolism can provide insights into folate's role in CRC.

    Objectives: Our aim was to perform a genome-wide interaction analysis to identify genetic variants that may modify the association of folate on CRC risk.

    Methods: We applied traditional case-control logistic regression, joint 3-degree of freedom, and a 2-step weighted hypothesis approach to test the interactions of common variants (allele frequency >1%) across the genome and dietary folate, folic acid supplement use, and total folate in relation to risk of CRC in 30,550 cases and 42,336 controls from 51 studies from 3 genetic consortia (CCFR, CORECT, GECCO).

    Results: Inverse associations of dietary, total folate, and folic acid supplement with CRC were found (odds ratio [OR]: 0.93; 95% confidence interval [CI]: 0.90, 0.96; and 0.91; 95% CI: 0.89, 0.94 per quartile higher intake, and 0.82 (95% CI: 0.78, 0.88) for users compared with nonusers, respectively). Interactions (P-interaction < 5×10-8) of folic acid supplement and variants in the 3p25.2 locus (in the region of Synapsin II [SYN2]/tissue inhibitor of metalloproteinase 4 [TIMP4]) were found using traditional interaction analysis, with variant rs150924902 (located upstream to SYN2) showing the strongest interaction. In stratified analyses by rs150924902 genotypes, folate supplementation was associated with decreased CRC risk among those carrying the TT genotype (OR: 0.82; 95% CI: 0.79, 0.86) but increased CRC risk among those carrying the TA genotype (OR: 1.63; 95% CI: 1.29, 2.05), suggesting a qualitative interaction (P-interaction = 1.4×10-8). No interactions were observed for dietary and total folate.

    Conclusions: Variation in 3p25.2 locus may modify the association of folate supplement with CRC risk. Experimental studies and studies incorporating other relevant omics data are warranted to validate this finding.

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  • 19. Bull, Caroline J.
    et al.
    Bell, Joshua A.
    Murphy, Neil
    Sanderson, Eleanor
    Davey Smith, George
    Timpson, Nicholas J.
    Banbury, Barbara L.
    Albanes, Demetrius
    Berndt, Sonja I.
    Bezieau, Stephane
    Bishop, D. Timothy
    Brenner, Hermann
    Buchanan, Daniel D.
    Burnett-Hartman, Andrea
    Casey, Graham
    Castellvi-Bel, Sergi
    Chan, Andrew T.
    Chang-Claude, Jenny
    Cross, Amanda J.
    de la Chapelle, Albert
    Figueiredo, Jane C.
    Gallinger, Steven J.
    Gapstur, Susan M.
    Giles, Graham G.
    Gruber, Stephen B.
    Gsur, Andrea
    Hampe, Jochen
    Hampel, Heather
    Harrison, Tabitha A.
    Hoffmeister, Michael
    Hsu, Li
    Huang, Wen-Yi
    Huyghe, Jeroen R.
    Jenkins, Mark A.
    Joshu, Corinne E.
    Keku, Temitope O.
    Kuhn, Tilman
    Kweon, Sun-Seog
    Le Marchand, Loic
    Li, Christopher I.
    Li, Li
    Lindblom, Annika
    Martin, Vicente
    May, Anne M.
    Milne, Roger L.
    Moreno, Victor
    Newcomb, Polly A.
    Offit, Kenneth
    Ogino, Shuji
    Phipps, Amanda I.
    Platz, Elizabeth A.
    Potter, John D.
    Qu, Conghui
    Quiros, J. Ramon
    Rennert, Gad
    Riboli, Elio
    Sakoda, Lori C.
    Schafmayer, Clemens
    Schoen, Robert E.
    Slattery, Martha L.
    Tangen, Catherine M.
    Tsilidis, Kostas K.
    Ulrich, Cornelia M.
    van Duijnhoven, Franzel J. B.
    van Guelpen, Bethany
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi. Umeå universitet, Medicinska fakulteten, Wallenberg centrum för molekylär medicin vid Umeå universitet (WCMM).
    Visvanathan, Kala
    Vodicka, Pavel
    Vodickova, Ludmila
    Wang, Hansong
    White, Emily
    Wolk, Alicja
    Woods, Michael O.
    Wu, Anna H.
    Campbell, Peter T.
    Zheng, Wei
    Peters, Ulrike
    Vincent, Emma E.
    Gunter, Marc J.
    Adiposity, metabolites, and colorectal cancer risk: Mendelian randomization study2020Ingår i: BMC Medicine, E-ISSN 1741-7015, Vol. 18, nr 1, artikel-id 396Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background Higher adiposity increases the risk of colorectal cancer (CRC), but whether this relationship varies by anatomical sub-site or by sex is unclear. Further, the metabolic alterations mediating the effects of adiposity on CRC are not fully understood. Methods We examined sex- and site-specific associations of adiposity with CRC risk and whether adiposity-associated metabolites explain the associations of adiposity with CRC. Genetic variants from genome-wide association studies of body mass index (BMI) and waist-to-hip ratio (WHR, unadjusted for BMI; N = 806,810), and 123 metabolites from targeted nuclear magnetic resonance metabolomics (N = 24,925), were used as instruments. Sex-combined and sex-specific Mendelian randomization (MR) was conducted for BMI and WHR with CRC risk (58,221 cases and 67,694 controls in the Genetics and Epidemiology of Colorectal Cancer Consortium, Colorectal Cancer Transdisciplinary Study, and Colon Cancer Family Registry). Sex-combined MR was conducted for BMI and WHR with metabolites, for metabolites with CRC, and for BMI and WHR with CRC adjusted for metabolite classes in multivariable models. Results In sex-specific MR analyses, higher BMI (per 4.2 kg/m(2)) was associated with 1.23 (95% confidence interval (CI) = 1.08, 1.38) times higher CRC odds among men (inverse-variance-weighted (IVW) model); among women, higher BMI (per 5.2 kg/m(2)) was associated with 1.09 (95% CI = 0.97, 1.22) times higher CRC odds. WHR (per 0.07 higher) was more strongly associated with CRC risk among women (IVW OR = 1.25, 95% CI = 1.08, 1.43) than men (IVW OR = 1.05, 95% CI = 0.81, 1.36). BMI or WHR was associated with 104/123 metabolites at false discovery rate-corrected P <= 0.05; several metabolites were associated with CRC, but not in directions that were consistent with the mediation of positive adiposity-CRC relations. In multivariable MR analyses, associations of BMI and WHR with CRC were not attenuated following adjustment for representative metabolite classes, e.g., the univariable IVW OR for BMI with CRC was 1.12 (95% CI = 1.00, 1.26), and this became 1.11 (95% CI = 0.99, 1.26) when adjusting for cholesterol in low-density lipoprotein particles. Conclusions Our results suggest that higher BMI more greatly raises CRC risk among men, whereas higher WHR more greatly raises CRC risk among women. Adiposity was associated with numerous metabolic alterations, but none of these explained associations between adiposity and CRC. More detailed metabolomic measures are likely needed to clarify the mechanistic pathways.

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  • 20. Butt, Julia
    et al.
    Jenab, Mazda
    Pawlita, Michael
    Overvad, Kim
    Tjonneland, Anne
    Olsen, Anja
    Boutron-Ruault, Marie-Christine
    Carbonnel, Franck
    Mancini, Francesca Romana
    Kaaks, Rudolf
    Kühn, Tilman
    Boeing, Heiner
    Trichopoulou, Antonia
    Karakatsani, Anna
    Palli, Domenico
    Pala, Valeria Maria
    Tumino, Rosario
    Sacerdote, Carlotta
    Panico, Salvatore
    Bueno-de-Mesquita, Bas
    van Gils, Carla H.
    Vermeulen, Roel C. H.
    Weiderpass, Elisabete
    Quiros, Jose Ramon
    Duell, Eric Jeffrey
    Sanchez, Maria-Jose
    Dorronsoro, Miren
    Maria Huerta, Jose
    Ardanaz, Eva
    van Guelpen, Bethany
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Harlid, Sophia
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Perez-Cornago, Aurora
    Gunter, Marc J.
    Murphy, Neil
    Freisling, Heinz
    Aune, Dagfinn
    Waterboer, Tim
    Hughes, David J.
    Antibody Responses to Fusobacterium nucleatum Proteins in Prediagnostic Blood Samples are not Associated with Risk of Developing Colorectal Cancer2019Ingår i: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 28, nr 9, s. 1552-1555Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: There is a lack of prospective data on the potential association of Fusobacterium nucleatum (F. nucleatum) and colorectal cancer risk. In this study, we assessed whether antibody responses to F. nucleatum are associated with colorectal cancer risk in prediagnostic serum samples in the European Prospective Investigation into Nutrition and Cancer (EPIC) cohort.

    Methods: We applied a multiplex serology assay to simultaneously measure antibody responses to 11 F. nucleatum antigens in prediagnostic serum samples from 485 colorectal cancer cases and 485 matched controls. Conditional logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CI).

    Results: We observed neither a statistically significant colorectal cancer risk association for antibodies to individual F. nucleatum proteins nor for combined positivity to any of the 11 proteins (OR, 0.81; 95% CI, 0.62–1.06).

    Conclusions: Antibody responses to F. nucleatum proteins in prediagnostic serum samples from a subset of colorectal cancer cases and matched controls within the EPIC study were not associated with colorectal cancer risk.

    Impact: Our findings in prospectively ascertained serum samples contradict the existing literature on the association of F. nucleatum with colorectal cancer risk. Future prospective studies, specifically detecting F. nucleatum in stool or tissue biopsies, are needed to complement our findings.

  • 21. Butt, Julia
    et al.
    Jenab, Mazda
    Pawlita, Michael
    Tjonneland, Anne
    Kyro, Cecilie
    Boutron-Ruault, Marie-Christine
    Carbonnel, Franck
    Dong, Catherine
    Kaaks, Rudolf
    Kuhn, Tilman
    Boeing, Heiner
    Schulze, Matthias B.
    Trichopoulou, Antonia
    Karakatsani, Anna
    La Vecchia, Carlo
    Palli, Domenico
    Agnoli, Claudia
    Tumino, Rosario
    Sacerdote, Carlotta
    Panico, Salvatore
    Bueno-de-Mesquita, Bas
    Vermeulen, Roel
    Gram, Inger T.
    Weiderpass, Elisabete
    Borch, Kristin Benjaminsen
    Quiros, Jose Ramon
    Agudo, Antonio
    Rodriguez-Barranco, Miguel
    Santiuste, Carmen
    Ardanaz, Eva
    van Guelpen, Bethany
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi. Umeå universitet, Medicinska fakulteten, Wallenberg centrum för molekylär medicin vid Umeå universitet (WCMM).
    Harlid, Sophia
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Imaz, Liher
    Perez-Cornago, Aurora
    Gunter, Marc J.
    Zouiouich, Semi
    Park, Jin Young
    Riboli, Elio
    Cross, Amanda J.
    Heath, Alicia K.
    Waterboer, Tim
    Hughes, David J.
    Antibody Responses to Helicobacter pylori and Risk of Developing Colorectal Cancer in a European Cohort2020Ingår i: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 29, nr 7, s. 1475-1481Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: While Helicobacter pylori (H. pylori) is the major cause of gastric cancer, it has also been suggested to be involved in colorectal cancer development. However, prospective studies addressing H. pylori and colorectal cancer are sparse and inconclusive. We assessed the association of antibody responses to H. pylori proteins with colorectal cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.

    Methods: We applied H. pylori multiplex serology to measure antibody responses to 13 H. pylori proteins in prediagnostic serum samples from 485 colorectal cancer cases and 485 matched controls nested within the EPIC study. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using multivariable conditional logistic regression to estimate the association of H. pylori overall and protein-specific seropositivity with odds of developing colorectal cancer.

    Results: Fifty-one percent of colorectal cancer cases were H. pylori seropositive compared with 44% of controls, resulting in an OR of 1.36 (95% CI, 1.00-1.85). Among the 13 individual H. pylori proteins, the association was driven mostly by seropositivity to Helicobacter cysteine-rich protein C (HcpC; OR: 1.66; 95% CI, 1.19-2.30) and Vacuolating cytotoxin A (VacA) (OR: 1.34; 95% CI, 0.99-1.82), the latter being nonstatistically significant only in the fully adjusted model.

    Conclusions: In this prospective multicenter European study, antibody responses to H. pylori proteins, specifically HcpC and VacA, were associated with an increased risk of developing colorectal cancer. Impact: Biological mechanisms for a potential causal role of H. pylori in colorectal carcinogenesis need to be elucidated, and subsequently whether H. pylori eradication may decrease colorectal cancer incidence.

  • 22.
    Carreras-Torres, Robert
    et al.
    Colorectal Cancer Group, ONCOBELL Program, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain; Oncology Data Analytics Program, Catalan Institute of Oncology, L'Hospitalet de Llobregat, Barcelona, Spain; Digestive Diseases and Microbiota Group, Girona Biomedical Research Institute (IDIBGI), Salt, Girona, Spain.
    Kim, Andre E.
    Division of Biostatistics, Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, CA, Los Angeles, United States.
    Lin, Yi
    Public Health Sciences Division, Fred Hutchinson Cancer Research Center, WA, Seattle, United States.
    Díez-Obrero, Virginia
    Colorectal Cancer Group, ONCOBELL Program, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain; Oncology Data Analytics Program, Catalan Institute of Oncology, L'Hospitalet de Llobregat, Barcelona, Spain; Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), Madrid, Spain.
    Bien, Stephanie A.
    Public Health Sciences Division, Fred Hutchinson Cancer Research Center, WA, Seattle, United States.
    Qu, Conghui
    Public Health Sciences Division, Fred Hutchinson Cancer Research Center, WA, Seattle, United States.
    Wang, Jun
    Division of Biostatistics, Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, CA, Los Angeles, United States.
    Dimou, Niki
    Nutrition and Metabolism Branch, International Agency for Research on Cancer, Lyon, France.
    Aglago, Elom K.
    Nutrition and Metabolism Branch, International Agency for Research on Cancer, Lyon, France.
    Albanes, Demetrius
    Division of Cancer Epidemiology and Genetics, NCI, NIH, MD, Bethesda, Liberia.
    Arndt, Volker
    Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.
    Baurley, James W.
    Bioinformatics and Data Science Research Center, Bina Nusantara University, Jakarta, Indonesia.
    Berndt, Sonja I.
    Division of Cancer Epidemiology and Genetics, NCI, NIH, MD, Bethesda, Liberia.
    Bézieau, Stéphane
    Service de Génétique Médicale, Centre Hospitalier Universitaire (CHU) Nantes, Nantes, France.
    Bishop, D Timothy
    Leeds Institute of Cancer and Pathology, University of Leeds, Leeds, United Kingdom.
    Bouras, Emmanouil
    Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece.
    Brenner, Hermann
    Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany; Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany; German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.
    Budiarto, Arif
    Bioinformatics and Data Science Research Center, Bina Nusantara University, Jakarta, Indonesia.
    Campbell, Peter T.
    Behavioral and Epidemiology Research Group, American Cancer Society, Atlanta, Georgia.
    Casey, Graham
    Center for Public Health Genomics, Department of Public Health Sciences, University of Virginia, VA, Charlottesville, United States.
    Chan, Andrew T.
    Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, MA, Boston, United States.
    Chang-Claude, Jenny
    Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
    Chen, Xuechen
    Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.
    Conti, David V.
    Division of Biostatistics, Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, CA, Los Angeles, United States.
    Dampier, Christopher H.
    Department of General Surgery, University of Virginia School of Medicine, VA, Charlottesville, United States.
    Devall, Matthew A M
    Center for Public Health Genomics, Department of Public Health Sciences, University of Virginia, VA, Charlottesville, United States.
    Drew, David A.
    Clinical & Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, MA, Boston, United States.
    Figueiredo, Jane C.
    Department of Medicine, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, CA, Los Angeles, United States.
    Gallinger, Steven
    Lunenfeld Tanenbaum Research Institute, University of Toronto, Mount Sinai Hospital, ON, Toronto, Canada.
    Giles, Graham G.
    Cancer Epidemiology Division, Cancer Council Victoria, VIC, Melbourne, Australia.
    Gruber, Stephen B.
    Department of Medical Oncology & Therapeutics Research, City of Hope National Medical Center, Duarte, California.
    Gsur, Andrea
    Institute of Cancer Research, Department of Medicine I, Medical University Vienna, Vienna, Austria.
    Gunter, Marc J.
    Nutrition and Metabolism Branch, International Agency for Research on Cancer, Lyon, France.
    Harrison, Tabitha A.
    Public Health Sciences Division, Fred Hutchinson Cancer Research Center, WA, Seattle, United States.
    Hidaka, Akihisa
    Public Health Sciences Division, Fred Hutchinson Cancer Research Center, WA, Seattle, United States.
    Hoffmeister, Michael
    Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.
    Huyghe, Jeroen R.
    Public Health Sciences Division, Fred Hutchinson Cancer Research Center, WA, Seattle, United States.
    Jenkins, Mark A.
    Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, VIC, Melbourne, Australia.
    Jordahl, Kristina M.
    Public Health Sciences Division, Fred Hutchinson Cancer Research Center, WA, Seattle, United States.
    Kawaguchi, Eric
    Division of Biostatistics, Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, CA, Los Angeles, United States.
    Keku, Temitope O.
    Center for Gastrointestinal Biology and Disease, University of North Carolina, Chapel Hill, NC, United States.
    Kundaje, Anshul
    Department of Genetics, Department of Computer Science, Stanford University, CA, Stanford, United States.
    Le Marchand, Loic
    University of Hawaii Cancer Center, HI, Honolulu, United States.
    Lewinger, Juan Pablo
    Division of Biostatistics, Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, CA, Los Angeles, United States.
    Li, Li
    Department of Family Medicine, University of Virginia, VA, Charlottesville, United States.
    Mahesworo, Bharuno
    Bioinformatics and Data Science Research Center, Bina Nusantara University, Jakarta, Indonesia.
    Morrison, John L.
    Division of Biostatistics, Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, CA, Los Angeles, United States.
    Murphy, Neil
    Nutrition and Metabolism Branch, International Agency for Research on Cancer, Lyon, France.
    Nan, Hongmei
    Department of Epidemiology, Richard M. Fairbanks School of Public Health, IN, Indianapolis, United States.
    Nassir, Rami
    Department of Pathology, School of Medicine, Umm Al-Qura'a University, Saudi Arabia.
    Newcomb, Polly A.
    Public Health Sciences Division, Fred Hutchinson Cancer Research Center, WA, Seattle, United States.
    Obón-Santacana, Mireia
    Colorectal Cancer Group, ONCOBELL Program, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain; Oncology Data Analytics Program, Catalan Institute of Oncology, L'Hospitalet de Llobregat, Barcelona, Spain; Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), Madrid, Spain.
    Ogino, Shuji
    Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, MA, Boston, United States; Department of Oncologic Pathology, Dana-Farber Cancer Institute, MA, Boston, United States; Department of Epidemiology, Harvard T.H. Chan School of Public Health, MA, Boston, United States; Broad Institute of MIT and Harvard, MA, Cambridge, United States.
    Ose, Jennifer
    Huntsman Cancer Institute, UT, Salt Lake City, United States; Department of Population Health Sciences, University of Utah, UT, Salt Lake City, United States.
    Pai, Rish K.
    Department of Laboratory Medicine and Pathology, Mayo Clinic Arizona, AZ, Scottsdale, United States.
    Palmer, Julie R.
    Slone Epidemiology Center at Boston University, MA, Boston, United States.
    Papadimitriou, Nikos
    Nutrition and Metabolism Branch, International Agency for Research on Cancer, Lyon, France.
    Pardamean, Bens
    Bioinformatics and Data Science Research Center, Bina Nusantara University, Jakarta, Indonesia.
    Peoples, Anita R.
    Huntsman Cancer Institute, UT, Salt Lake City, United States.
    Pharoah, Paul D P
    Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom.
    Platz, Elizabeth A.
    Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, MD, Baltimore, Liberia.
    Rennert, Gad
    Department of Community Medicine and Epidemiology, Lady Davis Carmel Medical Center, Haifa, Israel.
    Ruiz-Narvaez, Edward
    Department of Nutritional Sciences, University of Michigan School of Public Health, MI, Ann Arbor, United States.
    Sakoda, Lori C.
    Division of Research, Kaiser Permanente Northern California, CA, Oakland, United States.
    Scacheri, Peter C.
    Department of Genetics and Genome Sciences, Case Western Reserve University, OH, Cleveland, United States.
    Schmit, Stephanie L.
    Genomic Medicine Institute, Cleveland Clinic, OH, Cleveland, United States; Population and Cancer Prevention Program, Case Comprehensive Cancer Center, OH, Cleveland, United States.
    Schoen, Robert E.
    Department of Medicine and Epidemiology, University of Pittsburgh Medical Center, PA, Pittsburgh, United States.
    Shcherbina, Anna
    Biomedical Informatics Program, Dept. of Biomedical Data Sciences, Stanford University, CA, Stanford, United States.
    Slattery, Martha L.
    Department of Internal Medicine, University of Utah, UT, Salt Lake City, United States.
    Stern, Mariana C.
    Division of Biostatistics, Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, CA, Los Angeles, United States.
    Su, Yu-Ru
    Public Health Sciences Division, Fred Hutchinson Cancer Research Center, WA, Seattle, United States.
    Tangen, Catherine M.
    SWOG Statistical Center, Fred Hutchinson Cancer Research Center, WA, Seattle, United States.
    Thomas, Duncan C.
    Division of Biostatistics, Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, CA, Los Angeles, United States.
    Tian, Yu
    Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany; School of Public Health, Capital Medical University, Beijing, China.
    Tsilidis, Konstantinos K.
    Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece; Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom.
    Ulrich, Cornelia M.
    Huntsman Cancer Institute, UT, Salt Lake City, United States; Department of Population Health Sciences, University of Utah, UT, Salt Lake City, United States.
    van Duijnhoven, Fränzel J B
    Division of Human Nutrition and Health, Wageningen University & Research, Wageningen, Netherlands.
    van Guelpen, Bethany
    Umeå universitet, Medicinska fakulteten, Wallenberg centrum för molekylär medicin vid Umeå universitet (WCMM). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Visvanathan, Kala
    Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, MD, Baltimore, Liberia.
    Vodicka, Pavel
    Department of Molecular Biology of Cancer, Institute of Experimental Medicine of the Czech Academy of Sciences, Prague, and Biomedical Center, Medical Faculty, Pilsen, Czech Republic.
    Cenggoro, Tjeng Wawan
    Bioinformatics and Data Science Research Center, Bina Nusantara University, Jakarta, Indonesia.
    Weinstein, Stephanie J.
    Division of Cancer Epidemiology and Genetics, NCI, NIH, MD, Bethesda, Liberia.
    White, Emily
    Public Health Sciences Division, Fred Hutchinson Cancer Research Center, WA, Seattle, United States.
    Wolk, Alicja
    Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Woods, Michael O.
    Memorial University of Newfoundland, Discipline of Genetics, St. John's, Canada.
    Hsu, Li
    Public Health Sciences Division, Fred Hutchinson Cancer Research Center, WA, Seattle, United States.
    Peters, Ulrike
    Public Health Sciences Division, Fred Hutchinson Cancer Research Center, WA, Seattle, United States; School of Public Health, University of Washington, WA, Seattle, United States.
    Moreno, Victor
    Colorectal Cancer Group, ONCOBELL Program, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain; Oncology Data Analytics Program, Catalan Institute of Oncology, L'Hospitalet de Llobregat, Barcelona, Spain; Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), Madrid, Spain; Department of Clinical Sciences, Faculty of Medicine, University of Barcelona, Barcelona, Spain.
    Gauderman, W. James
    Division of Biostatistics, Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, CA, Los Angeles, United States.
    Genome-wide interaction study with smoking for colorectal cancer risk identifies novel genetic loci related to tumor suppression, inflammation, and immune response2023Ingår i: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 32, nr 3, s. 315-328Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Tobacco smoking is an established risk factor for colorectal cancer. However, genetically defined population subgroups may have increased susceptibility to smoking-related effects on colorectal cancer.

    METHODS: A genome-wide interaction scan was performed including 33,756 colorectal cancer cases and 44,346 controls from three genetic consortia.

    RESULTS: Evidence of an interaction was observed between smoking status (ever vs. never smokers) and a locus on 3p12.1 (rs9880919, P = 4.58 × 10-8), with higher associated risk in subjects carrying the GG genotype [OR, 1.25; 95% confidence interval (CI), 1.20-1.30] compared with the other genotypes (OR <1.17 for GA and AA). Among ever smokers, we observed interactions between smoking intensity (increase in 10 cigarettes smoked per day) and two loci on 6p21.33 (rs4151657, P = 1.72 × 10-8) and 8q24.23 (rs7005722, P = 2.88 × 10-8). Subjects carrying the rs4151657 TT genotype showed higher risk (OR, 1.12; 95% CI, 1.09-1.16) compared with the other genotypes (OR <1.06 for TC and CC). Similarly, higher risk was observed among subjects carrying the rs7005722 AA genotype (OR, 1.17; 95% CI, 1.07-1.28) compared with the other genotypes (OR <1.13 for AC and CC). Functional annotation revealed that SNPs in 3p12.1 and 6p21.33 loci were located in regulatory regions, and were associated with expression levels of nearby genes. Genetic models predicting gene expression revealed that smoking parameters were associated with lower colorectal cancer risk with higher expression levels of CADM2 (3p12.1) and ATF6B (6p21.33).

    CONCLUSIONS: Our study identified novel genetic loci that may modulate the risk for colorectal cancer of smoking status and intensity, linked to tumor suppression and immune response.

    IMPACT: These findings can guide potential prevention treatments.

  • 23.
    Dahlin, Anna M
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Henriksson, Maria L
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Van Guelpen, Bethany
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Stenling, Roger
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Öberg, Åke
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Rutegård, Jörgen
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Palmqvist, Richard
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Colorectal cancer prognosis depends on T-cell infiltration and molecular characteristics of the tumor2011Ingår i: Modern Pathology, ISSN 0893-3952, E-ISSN 1530-0285, Vol. 24, s. 671-682Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The aim of this study was to relate the density of tumor infiltrating T cells to cancer-specific survival in colorectal cancer, taking into consideration the CpG island methylator phenotype (CIMP) and microsatellite instability (MSI) screening status. The T-cell marker CD3 was stained by immunohistochemistry in 484 archival tumor tissue samples. T-cell density was semiquantitatively estimated and scored 1-4 in the tumor front and center (T cells in stroma), and intraepithelially (T cells infiltrating tumor cell nests). Total CD3 score was calculated as the sum of the three CD3 scores (range 3-12). MSI screening status was assessed by immunohistochemistry. CIMP status was determined by quantitative real-time PCR (MethyLight) using an eight-gene panel. We found that patients whose tumors were highly infiltrated by T cells (total CD3 score ≥7) had longer survival compared with patients with poorly infiltrated tumors (total CD3 score ≤4). This finding was statistically significant in multivariate analyses (multivariate hazard ratio, 0.57; 95% confidence interval, 0.31-1.00). Importantly, the finding was consistent in rectal cancer patients treated with preoperative radiotherapy. Although microsatellite unstable tumor patients are generally considered to have better prognosis, we found no difference in survival between microsatellite unstable and microsatellite stable (MSS) colorectal cancer patients with similar total CD3 scores. Patients with MSS tumors highly infiltrated by T cells had better prognosis compared with intermediately or poorly infiltrated microsatellite unstable tumors (log rank P=0.013). Regarding CIMP status, CIMP-low was associated with particularly poor prognosis in patients with poorly infiltrated tumors (multivariate hazard ratio for CIMP-low versus CIMP-negative, 3.07; 95% confidence interval, 1.53-6.15). However, some subset analyses suffered from low power and are in need of confirmation by independent studies. In conclusion, patients whose tumors are highly infiltrated by T cells have a beneficial prognosis, regardless of MSI, whereas the role of CIMP status in this context is less clear.

  • 24.
    Dahlin, Anna M
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Palmqvist, Richard
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Henriksson, Maria L
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Jacobsson, Maria
    Eklöf, Vincy
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Rutegård, Jörgen
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Öberg, Åke
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Van Guelpen, Bethany
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    The role of the CpG island methylator phenotype in colorectal cancer prognosis depends on microsatellite instability screening status2010Ingår i: Clinical Cancer Research, ISSN 1078-0432, E-ISSN 1557-3265, Vol. 16, nr 6, s. 1845-1855Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    PURPOSE: The aim of this study was to relate the CpG island methylator phenotype (CIMP; characterized by extensive promoter hypermethylation) to cancer-specific survival in colorectal cancer, taking into consideration relevant clinicopathologic factors, such as microsatellite instability (MSI) screening status and the BRAF V600E mutation.

    EXPERIMENTAL DESIGN: Archival tumor samples from 190 patients from the Northern Sweden Health and Disease Study (NSHDS) and 414 patients from the Colorectal Cancer in Umeå Study (CRUMS), including 574 with cancer-specific survival data, were analyzed for an eight-gene CIMP panel using quantitative real-time PCR (MethyLight). MSI screening status was assessed by immunohistochemistry.

    RESULTS: CIMP-low patients had a shorter cancer-specific survival compared with CIMP-negative patients (multivariate hazard ratio in NSHDS, 2.01; 95% confidence interval, 1.20-3.37; multivariate hazard ratio in CRUMS, 1.48; 95% confidence interval, 1.00-2.22). This result was similar in subgroups based on MSI screening status and was statistically significant in microsatellite stable (MSS) tumors in NSHDS. For CIMP-high patients, a shorter cancer-specific survival compared with CIMP-negative patients was observed in the MSS subgroup. Statistical significance was lost after adjusting for the BRAF mutation, but the main findings were generally unaffected.

    CONCLUSIONS: In this study, we found a poor prognosis in CIMP-low patients regardless of MSI screening status, and in CIMP-high patients with MSS. Although not consistently statistically significant, these results were consistent in two separate patient groups and emphasize the potential importance of CIMP and MSI status in colorectal cancer research.

  • 25.
    Dahlin, Anna M
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Van Guelpen, Bethany
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Hultdin, Johan
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Johansson, Ingegerd
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi, Kariologi.
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Palmqvist, Richard
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Plasma vitamin B12 concentrations and the risk of colorectal cancer: a nested case-referent study2008Ingår i: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 32, nr 2, s. 304-314Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    In this nested case-referent study, we related plasma concentrations of vitamin B12 to the risk of colorectal cancer, taking into consideration prediagnostic plasma folate and total homocysteine concentrations. Subjects were 226 cases and double matched referents from the population-based Northern Sweden Health and Disease Study. Follow-up times from recruitment to diagnosis ranged from 0.1 to 12.7 years, with a median of 4.2 years. Plasma vitamin B12 concentrations were inversely associated with the risk of rectal cancer: univariate odds ratio for the highest versus lowest quintile 0.34 (95% confidence interval (95% CI) 0.13-0.83), p(trend) = 0.004. Risk estimates were attenuated slightly but remained statistically significant after adjustment for body mass index, current smoking, recreational and occupational physical activity, alcohol intake and prediagnostic plasma folate and total homocysteine concentrations: OR 0.30 (95% CI 0.08-0.99), p(trend) = 0.025. The corresponding univariate and fully adjusted odds ratios for colon cancer were 1.25 (CI 0.66-2.36), p(trend) = 0.185 and 1.42 (CI 0.67-3.05), p(trend) = 0.113, respectively. The observed over-risk was attributable to left-sided colon cancer. Interaction analyses including vitamin B12, folate and homocysteine were in line with the results for vitamin B12 alone. In conclusion, these results suggest that increasing levels of plasma vitamin B12, alone or together with other factors involved in one-carbon metabolism, may reduce the risk of rectal cancer, whereas for colon cancer, the association appears to be less clear.

  • 26. de Batlle, J.
    et al.
    Ferrari, P.
    Chajes, V.
    Park, J. Y.
    Slimani, N.
    McKenzie, F.
    Overvad, K.
    Roswall, N.
    Tjønneland, A.
    Boutron-Ruault, M. C.
    Clavel-Chapelon, F.
    Fagherazzi, G.
    Katzke, V.
    Kaaks, R.
    Bergmann, M. M.
    Trichopoulou, A.
    Lagiou, P.
    Trichopoulos, D.
    Palli, D.
    Sieri, S.
    Panico, S.
    Tumino, R.
    Vineis, P.
    Bueno-de-Mesquita, H. B.
    Peeters, P. H.
    Hjartåker, A.
    Engeset, D.
    Weiderpass, E.
    Sánchez, S.
    Travier, N.
    Sanchez, M. J.
    Amiano, P.
    Chirlaque, M. D.
    Barricarte Gurrea, A.
    Khaw, K. T.
    Key, T. J.
    Bradbury, K. E.
    Ericson, U.
    Sonestedt, E.
    Van Guelpen, Bethany
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk farmakologi.
    Schneede, Jörn
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk farmakologi.
    Riboli, E.
    Romieu, I.
    Dietary folate intake and breast cancer risk: European prospective investigation into cancer and nutrition2015Ingår i: Journal of the National Cancer Institute, ISSN 0027-8874, E-ISSN 1460-2105, Vol. 107, nr 1, artikel-id dju367Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    There is limited evidence on the association between dietary folate intake and the risk of breast cancer (BC) by hormone receptor expression in the tumors. We investigated the relationship between dietary folate and BC risk using data from the European Prospective Investigation into Cancer and Nutrition (EPIC). A total of 367993 women age 35 to 70 years were recruited in 10 European countries. During a median follow-up of 11.5 years, 11575 women with BC were identified. Dietary folate intake was estimated from country-specific dietary questionnaires. Cox proportional hazards regression models were used to quantify the association between dietary variables and BC risk. BC tumors were classified by receptor status. Subgroup analyses were performed by menopausal status and alcohol intake. Intake of other B vitamins was considered. All statistical tests were two-sided. A borderline inverse association was observed between dietary folate and BC risk (hazard ratio comparing top vs bottom quintile [HRQ5-Q1] = 0.92, 95% CI = 0.83 to 1.01, P (trend) = .037). In premenopausal women, we observed a statistically significant trend towards lower risk in estrogen receptor-negative BC (HRQ5-Q1 = 0.66, 95% CI = 0.45 to 0.96, P (trend) = .042) and progesterone receptor-negative BC (HRQ5-Q1 = 0.70, 95% CI = 0.51 to 0.97, P (trend) = .021). No associations were found in postmenopausal women. A 14% reduction in BC risk was observed when comparing the highest with the lowest dietary folate tertiles in women having a high (> 12 alcoholic drinks/week) alcohol intake (HRT3-T1 = 0.86, 95% CI = 0.75 to 0.98, P (interaction) = .035). Higher dietary folate intake may be associated with a lower risk of sex hormone receptor-negative BC in premenopausal women.

  • 27.
    Dimou, Niki
    et al.
    Section of Nutrition and Metabolism, International Agency for Research on Cancer, Lyon, France.
    Yarmolinsky, James
    Department of Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom; MRC Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom.
    Bouras, Emmanouil
    Laboratory of Hygiene, Social & Preventive Medicine and Medical Statistics, Department of Medicine, School of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki, Greece; Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece.
    Tsilidis, Konstantinos K.
    Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece; Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom.
    Martin, Richard M.
    Department of Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom; MRC Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom; National Institute for Health Research (NIHR), Bristol Biomedical Research Centre, University Hospitals Bristol NHS Foundation Trust, University of Bristol, Bristol, United Kingdom.
    Lewis, Sarah J.
    Department of Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom; MRC Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom.
    Gram, Inger T.
    Department of Community Medicine, Faculty of Health Sciences, UiT The Arctic University of Norway, Tromsø, Norway.
    Bakker, Marije F.
    Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, University Utrecht, Utrecht, Netherlands.
    Brenner, Hermann
    Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany; Division of Preventive Oncology, German Cancer Research Center (DKFZ), National Center for Tumor Diseases (NCT), Heidelberg, Germany; German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.
    Figueiredo, Jane C.
    Department of Medicine, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, CA, Los Angeles, United States; Department of Preventive Medicine, Keck School of Medicine, University of Southern California, CA, Los Angeles, United States.
    Fortner, Renee T.
    Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
    Gruber, Stephen B.
    Center for Precision Medicine, City of Hope National Medical Center, CA, Duarte, United States.
    van Guelpen, Bethany
    Umeå universitet, Medicinska fakulteten, Wallenberg centrum för molekylär medicin vid Umeå universitet (WCMM). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Hsu, Li
    Public Health Sciences Division, Fred Hutchinson Cancer Research Center, WA, Seattle, United States; Department of Biostatistics, University of Washington, WA, Seattle, United States.
    Kaaks, Rudolf
    Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany; German Center for Lung Research (DZL), Translational Lung Research Center (TLRC), Heidelberg, Germany.
    Kweon, Sun-Seog
    Department of Preventive Medicine, Chonnam National University Medical School, Gwangju, South Korea; Jeonnam Regional Cancer Center, Chonnam National University Hwasun Hospital, Hwasun, South Korea.
    Lin, Yi
    Public Health Sciences Division, Fred Hutchinson Cancer Research Center, WA, Seattle, United States.
    Lindor, Noralane M.
    Department of Health Science Research, Mayo Clinic, AZ, Scottsdale, United States.
    Newcomb, Polly A.
    Public Health Sciences Division, Fred Hutchinson Cancer Research Center, WA, Seattle, United States; School of Public Health, University of Washington, WA, Seattle, United States.
    Sanchez, Maria-Jose
    Escuela Andaluza de Salud Publica (EASP), Granada, Spain; Instituto de Investigacion Biosanitaria ibs.GRANADA, Granada, Spain; Centro de Investigacion Biomedica en Red de Epidemiología y Salud Publica (CIBERESP), Madrid, Spain; Department of Preventive Medicine and Public Health, University of Granada, Granada, Spain.
    Severi, Gianluca
    CESP UMR1018, Universite Paris-Saclay, UVSQ, Inserm, Gustave Roussy, Villejuif, France; Department of Statistics, Computer Science and Applications “G. Parenti”, University of Florence, Florence, Italy.
    Tindle, Hilary A.
    General Internal Medicine, Vanderbilt University Medical Center, Vanderbilt University, TN, Nashville, United States.
    Tumino, Rosario
    Cancer Registry and Histopathology Department, Provincial Health Authority (ASP 7) Ragusa, Ragusa, Italy.
    Weiderpass, Elisabete
    International Agency for Research on Cancer, World Health Organization, Lyon, France.
    Gunter, Marc J.
    Section of Nutrition and Metabolism, International Agency for Research on Cancer, Lyon, France.
    Murphy, Neil
    Section of Nutrition and Metabolism, International Agency for Research on Cancer, Lyon, France.
    Causal effects of lifetime smoking on breast and colorectal cancer risk: Mendelian randomization study2021Ingår i: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 30, nr 5, s. 953-964Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Observational evidence has shown that smoking is a risk factor for breast and colorectal cancer. We used Mendelian randomization (MR) to examine causal associations between smoking and risks of breast and colorectal cancer.

    Methods: Genome-Wide Association Study summary data were used to identify genetic variants associated with lifetime amount of smoking (n ¼ 126 variants) and ever having smoked regularly (n ¼ 112 variants). Using two-sample MR, we examined these variants in relation to incident breast (122,977 cases/ 105,974 controls) and colorectal cancer (52,775 cases/45,940 controls).

    Results: In inverse-variance weighted models, a genetic predisposition to higher lifetime amount of smoking was positively associated with breast cancer risk [OR per 1-SD increment: 1.13; 95% confidence interval (CI): 1.00–1.26; P ¼ 0.04]; although heterogeneity was observed. Similar associations were found for estrogen receptor–positive and estrogen receptor–negative tumors. Higher lifetime amount of smoking was positively associated with colorectal cancer (OR per 1-SD increment, 1.21; 95% CI, 1.04–1.40; P ¼ 0.01), colon cancer (OR, 1.31; 95% CI, 1.11–1.55; P < 0.01), and rectal cancer (OR, 1.36; 95% CI, 1.07–1.73; P ¼ 0.01). Ever having smoked regularly was not associated with risks of breast (OR, 1.01; 95% CI, 0.90–1.14; P ¼ 0.85) or colorectal cancer (OR, 0.97; 95% CI, 0.86–1.10; P ¼ 0.68).

    Conclusions: These findings are consistent with prior observational evidence and support a causal role of higher lifetime smoking amount in the development of breast and colorectal cancer.

    Impact: The results from this comprehensive MR analysis indicate that lifetime smoking is a causal risk factor for these common malignancies.

  • 28.
    Edin, Sofia
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Gylling, Björn
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Li, Xingru
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Stenberg, Åsa
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Löfgren Burström, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Zingmark, Carl
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    van Guelpen, Bethany
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper. Umeå universitet, Medicinska fakulteten, Wallenberg centrum för molekylär medicin vid Umeå universitet (WCMM).
    Ljuslinder, Ingrid
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Ling, Agnes
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Palmqvist, Richard
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Opposing roles by KRAS and BRAF mutation on immune cell infiltration in colorectal cancer: possible implications for immunotherapy2023Ingår i: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: The immune response has important clinical value in colorectal cancer (CRC) in both prognosis and response to immunotherapy. This study aims to explore tumour immune cell infiltration in relation to clinically well-established molecular markers of CRC.

    Methods: Multiplex immunohistochemistry and multispectral imaging was used to evaluate tumour infiltration of cytotoxic T cells (CD8+), Th1 cells (T-bet+), T regulatory cells (FoxP3+), B cells (CD20+), and macrophages (CD68+) in a cohort of 257 CRC patients.

    Results: We found the expected association between higher immune-cell infiltration and microsatellite instability. Also, whereas BRAF-mutated tumours displayed increased immune-cell infiltration compared to BRAF wild-type tumours, the opposite was seen for KRAS-mutated tumours, differences that were most prominent for cytotoxic T cells and Th1 cells. The opposing relationships of BRAF and KRAS mutations with tumour infiltration of cytotoxic T cells was validated in an independent cohort of 608 CRC patients. A positive prognostic importance of cytotoxic T cells was found in wild-type as well as KRAS and BRAF-mutated CRCs in both cohorts.

    Conclusion: A combined evaluation of MSI status, KRAS and BRAF mutational status, and immune infiltration (cytotoxic T cells) may provide important insights to prognosis and response to immunotherapy in CRC.

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  • 29.
    Ekblom, Kim
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Hultdin, Johan
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Stegmayr, Birgitta
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Johansson, Ingegerd
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi, Kariologi.
    Van Guelpen, Bethany
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Weinehall, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och folkhälsovetenskap.
    Johansson, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Wiklund, Per-Gunnar
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Marklund, Stefan L
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Iron stores and HFE genotypes are not related to increased risk of ischemic stroke.: a prospective nested case-referent study2007Ingår i: Cerebrovascular Diseases, ISSN 1015-9770, E-ISSN 1421-9786, Vol. 24, nr 5, s. 405-411Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: High iron levels can increase the formation of noxious oxygen radicals, which are thought to contribute to cerebrovascular disease. The aim of this prospective study was to determine if iron status and HFE genotypes constitute risk factors for stroke.

    Methods: First-ever stroke cases (231 ischemic and 42 hemorrhagic) and matched double referents from the population-based Northern Sweden cohorts were studied in a nested case-referent setting.

    Results: For total iron binding capacity, an increased risk of ischemic stroke was seen in the highest quartile (OR 1.80; 95% CI 1.14-2.83; p for trend 0.012). The highest quartile of transferrin iron saturation showed a decreased risk of ischemic stroke in men (OR 0.44; 95% CI 0.22-0.87; p for trend 0.028), but not in women. There was an increased risk of hemorrhagic stroke in the second (OR 4.07; 95% CI 1.09-15.20) and third quartile (OR 4.22; 95% CI 1.08-16.42) of ferritin. Neither quartiles of plasma iron concentrations nor the HFE C282Y and H63D genotypes were associated with ischemic or hemorrhagic stroke.

    Conclusions: Iron stores were not positively related to increased risk of ischemic stroke. Furthermore, HFE genotypes did not influence the risk of ischemic or hemorrhagic stroke. Copyright (c) 2007 S. Karger AG, Basel.

  • 30.
    Ekblom, Kim
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Marklund, Stefan L.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Palmqvist, Richard
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Van Guelpen, Bethany
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Weinehall, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa.
    Hultdin, Johan
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Iron Biomarkers in Plasma, HFE Genotypes, and the Risk for Colorectal Cancer in a Prospective Setting2012Ingår i: Diseases of the Colon & Rectum, ISSN 0012-3706, E-ISSN 1530-0358, Vol. 55, nr 3, s. 337-344Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: High iron levels can increase the formation of noxious oxygen radicals, which are thought to promote carcinogenesis. OBJECTIVE: The aim of this prospective study was to determine whether iron biomarkers and HFE genotypes, which influence iron regulation, constitute risk factors for colorectal cancer. DESIGN: This is a prospective nested case-referent study. SETTINGS: The study was performed within the population-based Northern Sweden Health and Disease Study. PATIENTS: The study included 226 cases of colorectal cancer and 437 matched referents. MAIN OUTCOME MEASURES: Conditional regression analysis was performed. Adjustments for smoking, smoking and BMI, and HFE C282Y and H63D were performed. RESULTS: The highest quintile of total iron-binding capacity showed significantly higher risk for colorectal cancer, unadjusted OR 2.35 (95% CI 1.38-4.02). When stratified by sex, the findings were only present in women (OR 3.34 (95% CI 1.59-7.02)). Ferritin was associated with reduced risk throughout quintiles 2 to 5 both in univariate and multivariate models. LIMITATIONS: Colorectal cancer may influence iron markers because of occult bleeding. Homozygotes for HFE C282Y were too few to make conclusions for this group. The relatively short follow-up time might be insufficient to detect risk of iron biomarkers. CONCLUSIONS: High iron levels do not increase the risk of colorectal cancer. HFE genotypes influencing iron uptake had no effect on colorectal cancer risk.

  • 31.
    Eklöf, Vincy
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Van Guelpen, Bethany
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Hultdin, Johan
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Johansson, Ingegerd
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Palmqvist, Richard
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    The reduced folate carrier (RFC1) 80G>A and folate hydrolase 1 (FOLH1) 1561C>T polymorphisms and the risk of colorectal cancer: a nested case-referent study2008Ingår i: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 68, nr 5, s. 393-401Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective. Polymorphisms in genes involved in folate uptake and metabolism may affect folate status and, thereby, the risk of cancer. In this nested case‐referent study, we related two such polymorphisms, reduced folate carrier (RFC1) 80G>A and folate hydrolase 1 (FOLH1) 1561C>T, to the risk of colorectal cancer, taking into account pre‐diagnostic plasma folate and total homocysteine concentrations and the MTHFR 677C>T polymorphism, which were analysed in a previous study.

    Material and methods. Subjects were 220 cases and 414 matched referents from the population‐based Northern Sweden Health and Disease Study.

    Results. The RFC1 80A‐allele was associated with reduced plasma folate and elevated plasma total homocysteine concentrations, but the result was statistically significant only for folate. In contrast, the FOLH1 1561T‐allele was associated with higher plasma folate and reduced plasma total homocysteine concentrations, and the result was statistically significant only for homocysteine. Neither polymorphism was related to the risk of colorectal cancer, either in univariate analysis or after adjusting for body mass index, current smoking, recreational and occupational physical activity and alcohol intake. Further adjustment for folate or homocysteine status or the MTHFR 677C>T polymorphism did not affect risk estimates. Subjects with the RFC1 80AA genotype in combination with low plasma folate concentrations or the MTHFR 677TT genotype had a reduced risk of colorectal cancer of borderline statistical significance.

    Conclusions. These findings suggest that although the RFC1 80G>A and FOLH1 1561C>T polymorphisms may influence folate status, they are not likely to have a major independent role in the development of colorectal cancer.

    Read More: http://informahealthcare.com/doi/abs/10.1080/00365510701805431

  • 32. Eussen, Simone JPM
    et al.
    Nilsen, Roy M
    Midttun, Oivind
    Hustad, Steinar
    IJssennagger, Noortje
    Meyer, Klaus
    Fredriksen, Ase
    Ulvik, Arve
    Ueland, Per M
    Brennan, Paul
    Johansson, Mattias
    Bueno-de-Mesquita, Bas
    Vineis, Paolo
    Chuang, Shu-Chun
    Boutron-Ruault, Marie Christine
    Dossus, Laure
    Perquier, Florence
    Overvad, Kim
    Teucher, Birgit
    Grote, Verena A
    Trichopoulou, Antonia
    Adarakis, George
    Plada, Maria
    Sieri, Sabina
    Tumino, Rosario
    Santucci de Magistris, Maria
    Ros, Martine M
    Peeters, Petra HM
    Luisa Redondo, Maria
    Zamora-Ros, Raul
    Chirlaque, Maria-Dolores
    Ardanaz, Eva
    Sonestedt, Emily
    Ericson, Ulrika
    Schneede, Jörn
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk farmakologi.
    van Guelpen, Bethany
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Wark, Petra A
    Gallo, Valentina
    Norat, Teresa
    Riboli, Elio
    Vollset, Stein Emil
    North-south gradients in plasma concentrations of B-vitamins and other components of one-carbon metabolism in Western Europe: results from the European Prospective Investigation into Cancer and Nutrition (EPIC) Study2013Ingår i: British Journal of Nutrition, ISSN 0007-1145, E-ISSN 1475-2662, Vol. 110, nr 2, s. 363-374Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Different lifestyle patterns across Europe may influence plasma concentrations of B-vitamins and one-carbon metabolites and their relation to chronic disease. Comparison of published data on one-carbon metabolites in Western European regions is difficult due to differences in sampling procedures and analytical methods between studies. The present study aimed, to compare plasma concentrations of one-carbon metabolites in Western European regions with one laboratory performing all biochemical analyses. We performed the present study in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort among 5446 presumptively healthy individuals. Quantile regression was used to compare sex-specific median concentrations between Northern (Denmark and Sweden), Central (France, Germany, The Netherlands and United Kingdom) and Southern (Greece, Spain and Italy) European regions. The lowest folate concentrations were observed in Northern Europe (men, 10.4 nmol/l; women, 10.7 nmol/l) and highest concentrations in Central Europe. Cobalamin concentrations were slightly higher in Northern Europe (men, 330 pmol/l; women, 352 pmol/l) compared with Central and Southern Europe, but did not show a clear north-south gradient. Vitamin B-2 concentrations were highest in Northern Europe (men, 22.2 nmol/l; women, 26.0 nmol/l) and decreased towards Southern Europe (P-trend < 0.001). Vitamin B-6 concentrations were highest in Central Europe in men (77.3 nmol/l) and highest in the North among women (70.4 nmol/l), with decreasing concentrations towards Southern Europe in women (P-trend < 0.001). In men, concentrations of serine, glycine and sarcosine increased from the north to south. In women, sarcosine increased from Northern to Southern Europe. These findings may provide relevant information for the study of regional differences of chronic disease incidence in association with lifestyle.

  • 33. Eussen, Simone JPM
    et al.
    Vollset, Stein Emil
    Hustad, Steinar
    Midttun, Øivind
    Meyer, Klaus
    Fredriksen, Ase
    Ueland, Per Magne
    Jenab, Mazda
    Slimani, Nadia
    Boffetta, Paolo
    Overvad, Kim
    Thorlacius-Ussing, Ole
    Tjønneland, Anne
    Olsen, Anja
    Clavel-Chapelon, Françoise
    Boutron-Ruault, Marie-Christine
    Morois, Sophie
    Weikert, Cornelia
    Pischon, Tobias
    Linseisen, Jakob
    Kaaks, Rudolf
    Trichopoulou, Antonia
    Zilis, Demosthenes
    Katsoulis, Michael
    Palli, Domenico
    Pala, Valeria
    Vineis, Paolo
    Tumino, Rosario
    Panico, Salvatore
    Peeters, Petra HM
    Bueno-de-Mesquita, H Bas
    van Duijnhoven, Fränzel JB
    Skeie, Guri
    Muñoz, Xavier
    Martínez, Carmen
    Dorronsoro, Miren
    Ardanaz, Eva
    Navarro, Carmen
    Rodríguez, Laudina
    Van Guelpen, Bethany
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Palmqvist, Richard
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Manjer, Jonas
    Ericson, Ulrika
    Bingham, Sheila
    Khaw, Kay-Tee
    Norat, Teresa
    Riboli, Elio
    Plasma vitamins B2, B6, and B12, and related genetic variants as predictors of colorectal cancer risk2010Ingår i: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 19, nr 10, s. 2549-2561Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    This European population-based study is the first to indicate that vitamin B2 is inversely associated with colorectal cancer, and is in agreement with previously suggested inverse associations of vitamin B6 with colorectal cancer.

  • 34. Eussen, Simone JPM
    et al.
    Vollset, Stein Emil
    Igland, Jannicke
    Meyer, Klaus
    Fredriksen, Ase
    Ueland, Per Magne
    Jenab, Mazda
    Slimani, Nadia
    Boffetta, Paolo
    Overvad, Kim
    Tjønneland, Anne
    Olsen, Anja
    Clavel-Chapelon, Françoise
    Boutron-Ruault, Marie-Christine
    Morois, Sophie
    Weikert, Cornelia
    Pischon, Tobias
    Linseisen, Jakob
    Kaaks, Rudolf
    Trichopoulou, Antonia
    Zilis, Demosthenes
    Katsoulis, Michael
    Palli, Domenico
    Berrino, Franco
    Vineis, Paolo
    Tumino, Rosario
    Panico, Salvatore
    Peeters, Petra HM
    Bueno-de-Mesquita, H Bas
    van Duijnhoven, Fränzel JB
    Gram, Inger Torhild
    Skeie, Guri
    Lund, Eiliv
    González, Carlos A
    Martínez, Carmen
    Dorronsoro, Miren
    Ardanaz, Eva
    Navarro, Carmen
    Rodríguez, Laudina
    Van Guelpen, Bethany
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Palmqvist, Richard
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Manjer, Jonas
    Ericson, Ulrika
    Bingham, Sheila
    Khaw, Kay-Tee
    Norat, Teresa
    Riboli, Elio
    Plasma folate, related genetic variants, and colorectal cancer risk in EPIC2010Ingår i: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 19, nr 5, s. 1328-1340Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Findings of the present study tend to weaken the evidence that folate plays an important role in CRC carcinogenesis. However, larger sample sizes are needed to adequately address potential gene-environment interactions.

  • 35.
    Fernandez-Rozadilla, Ceres
    et al.
    Edinburgh Cancer Research Centre, Institute of Genomics and Cancer, University of Edinburgh, Edinburgh, United Kingdom; Genomic Medicine Group, Instituto de Investigacion Sanitaria de Santiago, Santiago de Compostela, Spain.
    Timofeeva, Maria
    Colon Cancer Genetics Group, Medical Research Council Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, United Kingdom; Danish Institute for Advanced Study, Department of Public Health, University of Southern Denmark, Odense, Denmark.
    Chen, Zhishan
    Division of Epidemiology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt Epidemiology Center, Vanderbilt University Medical Center, TN, Nashville, United States.
    Law, Philip
    Division of Genetics and Epidemiology, Institute of Cancer Research, London, United Kingdom.
    Thomas, Minta
    Public Health Sciences Division, Fred Hutchinson Cancer Research Center, WA, Seattle, United States.
    Schmit, Stephanie
    Genomic Medicine Institute, Cleveland Clinic, OH, Cleveland, United States; Population and Cancer Prevention Program, Case Comprehensive Cancer Center, OH, Cleveland, United States.
    Díez-Obrero, Virginia
    Colorectal Cancer Group, ONCOBELL Program, Bellvitge Biomedical Research Institute, Barcelona, Spain; Oncology Data Analytics Program, Catalan Institute of Oncology, Barcelona, Spain; Consortium for Biomedical Research in Epidemiology and Public Health, Madrid, Madrid, Spain; Department of Clinical Sciences, Faculty of Medicine, University of Barcelona, Barcelona, Spain.
    Hsu, Li
    Public Health Sciences Division, Fred Hutchinson Cancer Research Center, WA, Seattle, United States; Department of Biostatistics, School of Public Health, University of Washington, WA, Seattle, United States.
    Fernandez-Tajes, Juan
    Edinburgh Cancer Research Centre, Institute of Genomics and Cancer, University of Edinburgh, Edinburgh, United Kingdom.
    Palles, Claire
    Institute of Cancer and Genomic Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom.
    Sherwood, Kitty
    Edinburgh Cancer Research Centre, Institute of Genomics and Cancer, University of Edinburgh, Edinburgh, United Kingdom.
    Briggs, Sarah
    Department of Public Health, Richard Doll Building, University of Oxford, Oxford, United Kingdom.
    Svinti, Victoria
    Colon Cancer Genetics Group, Medical Research Council Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, United Kingdom.
    Donnelly, Kevin
    Colon Cancer Genetics Group, Medical Research Council Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, United Kingdom.
    Farrington, Susan
    Colon Cancer Genetics Group, Medical Research Council Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, United Kingdom.
    Blackmur, James
    Colon Cancer Genetics Group, Medical Research Council Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, United Kingdom.
    Vaughan-Shaw, Peter
    Colon Cancer Genetics Group, Medical Research Council Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, United Kingdom.
    Shu, Xiao-ou
    Division of Epidemiology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt Epidemiology Center, Vanderbilt University Medical Center, TN, Nashville, United States.
    Long, Jirong
    Division of Epidemiology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt Epidemiology Center, Vanderbilt University Medical Center, TN, Nashville, United States.
    Cai, Qiuyin
    Division of Epidemiology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt Epidemiology Center, Vanderbilt University Medical Center, TN, Nashville, United States.
    Guo, Xingyi
    Division of Epidemiology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt Epidemiology Center, Vanderbilt University Medical Center, TN, Nashville, United States; Department of Biomedical Informatics, Vanderbilt University School of Medicine, TN, Nashville, United States.
    Lu, Yingchang
    Division of Epidemiology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt Epidemiology Center, Vanderbilt University Medical Center, TN, Nashville, United States.
    Broderick, Peter
    Division of Genetics and Epidemiology, Institute of Cancer Research, London, United Kingdom.
    Studd, James
    Division of Genetics and Epidemiology, Institute of Cancer Research, London, United Kingdom.
    Huyghe, Jeroen
    Public Health Sciences Division, Fred Hutchinson Cancer Research Center, WA, Seattle, United States.
    Harrison, Tabitha
    Public Health Sciences Division, Fred Hutchinson Cancer Research Center, WA, Seattle, United States.
    Conti, David
    Department of Preventive Medicine, USC Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, CA, Los Angeles, United States.
    Dampier, Christopher
    Center for Public Health Genomics, Department of Public Health Sciences, University of Virginia, VA, Charlottesville, United States.
    Devall, Mathew
    Center for Public Health Genomics, Department of Public Health Sciences, University of Virginia, VA, Charlottesville, United States.
    Schumacher, Fredrick
    Department of Population and Quantitative Health Sciences, Case Western Reserve University, OH, Cleveland, United States; Case Comprehensive Cancer Center, Case Western Reserve University, OH, Cleveland, United States.
    Melas, Marilena
    The Steve and Cindy Rasmussen Institute for Genomic Medicine, Nationwide Children’s Hospital, OH, Columbus, United States.
    Rennert, Gad
    Department of Community Medicine and Epidemiology, Lady Davis Carmel Medical Center, Haifa, Israel; Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel; Clalit National Cancer Control Center, Haifa, Israel.
    Obón-Santacana, Mireia
    Colorectal Cancer Group, ONCOBELL Program, Bellvitge Biomedical Research Institute, Barcelona, Spain; Oncology Data Analytics Program, Catalan Institute of Oncology, Barcelona, Spain; Consortium for Biomedical Research in Epidemiology and Public Health, Madrid, Spain.
    Martín-Sánchez, Vicente
    Consortium for Biomedical Research in Epidemiology and Public Health, Madrid, Madrid, Spain; Biomedicine Institute, University of León, León, Spain.
    Moratalla-Navarro, Ferran
    Colorectal Cancer Group, ONCOBELL Program, Bellvitge Biomedical Research Institute, Barcelona, Spain; Oncology Data Analytics Program, Catalan Institute of Oncology, Barcelona, Spain; Consortium for Biomedical Research in Epidemiology and Public Health, Madrid, Madrid, Spain; Department of Clinical Sciences, Faculty of Medicine, University of Barcelona, Barcelona, Spain.
    Oh, Jae Hwan
    Center for Colorectal Cancer, National Cancer Center Hospital, National Cancer Center, Gyeonggi-do, South Korea.
    Kim, Jeongseon
    Department of Cancer Biomedical Science, Graduate School of Cancer Science and Policy, National Cancer Center, Gyeonggi-do, South Korea.
    Jee, Sun Ha
    Department of Epidemiology and Health Promotion, Graduate School of Public Health, Yonsei University, Seoul, South Korea.
    Jung, Keum Ji
    Department of Epidemiology and Health Promotion, Graduate School of Public Health, Yonsei University, Seoul, South Korea.
    Kweon, Sun-Seog
    Department of Preventive Medicine, Chonnam National University Medical School, Gwangju, South Korea.
    Shin, Min-Ho
    Department of Preventive Medicine, Chonnam National University Medical School, Gwangju, South Korea.
    Shin, Aesun
    Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, South Korea; Cancer Research Institute, Seoul National University, Seoul, South Korea.
    Ahn, Yoon-Ok
    Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, South Korea.
    Kim, Dong-Hyun
    Department of Social and Preventive Medicine, Hallym University College of Medicine, Okcheon-dong, South Korea.
    Oze, Isao
    Division of Cancer Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya, Japan.
    Wen, Wanqing
    Division of Epidemiology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt Epidemiology Center, Vanderbilt University Medical Center, TN, Nashville, United States.
    Matsuo, Keitaro
    Division of Molecular and Clinical Epidemiology, Aichi Cancer Center Research Institute, Nagoya, Japan; Department of Epidemiology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
    Matsuda, Koichi
    Laboratory of Clinical Genome Sequencing, Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, University of Tokyo, Tokyo, Japan.
    Tanikawa, Chizu
    Laboratory of Genome Technology, Human Genome Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan.
    Ren, Zefang
    School of Public Health, Sun Yat-sen University, Guangzhou, China.
    Gao, Yu-Tang
    State Key Laboratory of Oncogenes and Related Genes and Department of Epidemiology, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
    Jia, Wei-Hua
    State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-sen University, Guangzhou, China.
    Hopper, John
    Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, VIC, Melbourne, Australia; Department of Epidemiology, School of Public Health and Institute of Health and Environment, Seoul National University, Seoul, South Korea.
    Jenkins, Mark
    Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, VIC, Melbourne, Australia.
    Win, Aung Ko
    Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, VIC, Melbourne, Australia.
    Pai, Rish
    Department of Laboratory Medicine and Pathology, Mayo Clinic Arizona, AZ, Scottsdale, United States.
    Figueiredo, Jane
    Department of Preventive Medicine, USC Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, CA, Los Angeles, United States; Department of Medicine, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, CA, Los Angeles, United States.
    Haile, Robert
    Division of Oncology, Department of Medicine, Cedars-Sinai Cancer Research Center for Health Equity, CA, Los Angeles, United States.
    Gallinger, Steven
    Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, ON, Toronto, Canada.
    Woods, Michael
    Division of Biomedical Sciences, Memorial University of Newfoundland, ON, St. John, Canada.
    Newcomb, Polly
    Public Health Sciences Division, Fred Hutchinson Cancer Research Center, WA, Seattle, United States; School of Public Health, University of Washington, WA, Seattle, United States.
    Duggan, David
    City of Hope National Medical Center, Translational Genomics Research Institute, AZ, Phoenix, United States.
    Cheadle, Jeremy
    Institute of Medical Genetics, Cardiff University, Cardiff, United Kingdom.
    Kaplan, Richard
    MRC Clinical Trials Unit, Medical Research Council, Cardiff, United Kingdom.
    Maughan, Timothy
    MRC Institute for Radiation Oncology, University of Oxford, Oxford, United Kingdom.
    Kerr, Rachel
    Department of Oncology, University of Oxford, Oxford, United Kingdom.
    Kerr, David
    Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom.
    Kirac, Iva
    Department of Surgical Oncology, University Hospital for Tumors, Sestre milosrdnice University Hospital Center, Zagreb, Croatia.
    Böhm, Jan
    Department of Pathology, Central Finland Health Care District, Jyväskylä, Finland.
    Mecklin, Lukka-Pekka
    Central Finland Health Care District, Jyväskylä, Finland.
    Jousilahti, Pekka
    Department of Health and Welfare, Finnish Institute for Health and Welfare, Helsinki, Finland.
    Knekt, Paul
    Department of Health and Welfare, Finnish Institute for Health and Welfare, Helsinki, Finland.
    Aaltonen, Lauri
    Department of Medical and Clinical Genetics, University of Helsinki, Helsinki, Finland; Genome-Scale Biology Research Program, University of Helsinki, Helsinki, Finland.
    Rissanen, Harri
    Department of Public Health and Welfare, Finnish Institute for Health and Welfare, Helsinki, Finland.
    Pukkala, Eero
    Finnish Cancer Registry, Institute for Statistical and Epidemiological Cancer Research, Helsinki, Finland; Faculty of Social Sciences, Tampere University, Tampere, Finland.
    Eriksson, Johan
    Folkhälsan Research Centre, University of Helsinki, Helsinki, Finland; Human Potential Translational Research Programme, National University of Singapore, Singapore, Singapore; Unit of General Practice and Primary Health Care, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
    Cajuso, Tatiana
    Department of Medical and Clinical Genetics, University of Helsinki, Helsinki, Finland; Genome-Scale Biology Research Program, University of Helsinki, Helsinki, Finland.
    Hänninen, Ulrika
    Department of Medical and Clinical Genetics, University of Helsinki, Helsinki, Finland; Genome-Scale Biology Research Program, University of Helsinki, Helsinki, Finland.
    Kondelin, Johanna
    Department of Medical and Clinical Genetics, University of Helsinki, Helsinki, Finland; Genome-Scale Biology Research Program, University of Helsinki, Helsinki, Finland.
    Palin, Kimmo
    Department of Medical and Clinical Genetics, University of Helsinki, Helsinki, Finland; Genome-Scale Biology Research Program, University of Helsinki, Helsinki, Finland.
    Tanskanen, Tomas
    Department of Medical and Clinical Genetics, University of Helsinki, Helsinki, Finland; Genome-Scale Biology Research Program, University of Helsinki, Helsinki, Finland.
    Renkonen-Sinisalo, Laura
    Department of Surgery, Abdominal Centre, Helsinki University Hospital, Helsinki, Finland.
    Zanke, Brent
    Department of Oncology, University of Toronto, ON, Toronto, Canada.
    Männistö, Satu
    Department of Public Health and Welfare, Finnish Institute for Health and Welfare, Helsinki, Finland.
    Albanes, Demetrius
    Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, MD, Bethesda, United States.
    Weinstein, Stephanie
    Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, MD, Bethesda, United States.
    Ruiz-Narvaez, Edward
    Department of Nutritional Sciences, School of Public Health, University of Michigan, MI, Ann Arbor, United States.
    Palmer, Julie
    Slone Epidemiology Center at Boston University, MA, Boston, United States; Department of Medicine, Boston University School of Medicine, MA, Boston, United States.
    Buchanan, Daniel
    Colorectal Oncogenomics Group, Department of Clinical Pathology, University of Melbourne, VIC, Parkville, Australia; University of Melbourne Centre for Cancer Research, Victorian Comprehensive Cancer Centre, VIC, Parkville, Australia; Genomic Medicine and Family Cancer Clinic, Royal Melbourne Hospital, VIC, Parkville, Australia.
    Platz, Elizabeth
    Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, MD, Baltimore, United States.
    Visvanathan, Kala
    Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, MD, Baltimore, United States.
    Ulrich, Cornelia
    Huntsman Cancer Institute and Department of Population Health Sciences, University of Utah, UT, Salt Lake City, United States.
    Siegel, Erin
    Cancer Epidemiology Program, H. Lee Moffitt Cancer Center and Research Institute, FL, Tampa, United States.
    Brezina, Stefanie
    Institute of Cancer Research, Department of Medicine I, Medical University Vienna, Vienna, Austria.
    Gsur, Andrea
    Institute of Cancer Research, Department of Medicine I, Medical University Vienna, Vienna, Austria.
    Campbell, Peter
    Department of Epidemiology and Population Health, Albert Einstein College of Medicine, NY, New York, United States.
    Chang-Claude, Jenny
    Division of Cancer Epidemiology, German Cancer Research Center, Heidelberg, Germany; University Medical Centre Hamburg-Eppendorf, University Cancer Centre Hamburg, Hamburg, Germany.
    Hoffmeister, Michael
    Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany.
    Brenner, Hermann
    Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany; Division of Preventive Oncology, German Cancer Research Center and National Center for Tumor Diseases, Heidelberg, Germany; German Cancer Consortium, German Cancer Research Center, Heidelberg, Germany.
    Slattery, Martha
    Department of Internal Medicine, University of Utah, UT, Salt Lake City, United States.
    Potter, John
    Public Health Sciences Division, Fred Hutchinson Cancer Research Center, WA, Seattle, United States; Research Centre for Hauora and Health, Massey University, Wellington, New Zealand.
    Tsilidis, Konstantinos
    Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece; Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom.
    Schulze, Matthias
    Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany; Institute of Nutritional Science, University of Potsdam, Potsdam, Germany.
    Gunter, Marc
    Nutrition and Metabolism Branch, International Agency for Research on Cancer, World Health Organization, Lyon, France.
    Murphy, Neil
    Nutrition and Metabolism Branch, International Agency for Research on Cancer, World Health Organization, Lyon, France.
    Castells, Antoni
    Gastroenterology Department, Hospital Clínic, Institut d’Investigacions Biomèdiques August Pi i Sunyer, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, University of Barcelona, Barcelona, Spain.
    Castellví-Bel, Sergi
    Gastroenterology Department, Hospital Clínic, Institut d’Investigacions Biomèdiques August Pi i Sunyer, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, University of Barcelona, Barcelona, Spain.
    Moreira, Leticia
    Gastroenterology Department, Hospital Clínic, Institut d’Investigacions Biomèdiques August Pi i Sunyer, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, University of Barcelona, Barcelona, Spain.
    Arndt, Volker
    Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany.
    Shcherbina, Anna
    Department of Genetics, Stanford University, CA, Stanford, United States.
    Stern, Mariana
    Department of Population and Public Health Sciences, USC Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, CA, Los Angeles, United States; Jeonnam Regional Cancer Center, Chonnam National University Hwasun Hospital, Hwasun, South Korea.
    Pardamean, Bens
    Bioinformatics and Data Science Research Center, Bina Nusantara University, Jakarta, Indonesia.
    Bishop, Timothy
    Leeds Institute of Medical Research at St James’s, University of Leeds, Leeds, United Kingdom.
    Giles, Graham
    Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, VIC, Melbourne, Australia; Cancer Epidemiology Division, Cancer Council Victoria, VIC, Melbourne, Australia; Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, VIC, Clayton, Australia.
    Southey, Melissa
    Cancer Epidemiology Division, Cancer Council Victoria, VIC, Melbourne, Australia; Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, VIC, Clayton, Australia; Department of Clinical Pathology, University of Melbourne, VIC, Melbourne, Australia.
    Idos, Gregory
    Department of Medical Oncology and Center For Precision Medicine, City of Hope National Medical Center, CA, Duarte, United States.
    McDonnell, Kevin
    Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel; Clalit National Cancer Control Center, Haifa, Israel; Department of Medical Oncology and Center For Precision Medicine, City of Hope National Medical Center, CA, Duarte, United States.
    Abu-Ful, Zomoroda
    Department of Community Medicine and Epidemiology, Lady Davis Carmel Medical Center, Haifa, Israel.
    Greenson, Joel
    Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel; Clalit National Cancer Control Center, Haifa, Israel; Department of Pathology, University of Michigan, MI, Ann Arbor, United States.
    Shulman, Katerina
    Department of Community Medicine and Epidemiology, Lady Davis Carmel Medical Center, Haifa, Israel.
    Lejbkowicz, Flavio
    Department of Community Medicine and Epidemiology, Lady Davis Carmel Medical Center, Haifa, Israel; Clalit National Cancer Control Center, Haifa, Israel; Clalit Health Services, Personalized Genomic Service, Lady Davis Carmel Medical Center, Haifa, Israel.
    Offit, Kenneth
    Clinical Genetics Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, NY, New York, United States; Department of Medicine, Weill Cornell Medical College, NY, New York, United States.
    Su, Yu-Ru
    Kaiser Permanente Washington Health Research Institute, WA, Seattle, United States.
    Steinfelder, Robert
    Public Health Sciences Division, Fred Hutchinson Cancer Research Center, WA, Seattle, United States.
    Keku, Temitope
    Center for Gastrointestinal Biology and Disease, University of North Carolina, NC, Chapel Hill, United States.
    van Guelpen, Bethany
    Umeå universitet, Medicinska fakulteten, Wallenberg centrum för molekylär medicin vid Umeå universitet (WCMM). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Hudson, Thomas
    Ontario Institute for Cancer Research, ON, Toronto, Canada.
    Hampel, Heather
    Division of Human Genetics, Department of Internal Medicine, Ohio State University Comprehensive Cancer Center, OH, Columbus, United States.
    Pearlman, Rachel
    Division of Human Genetics, Department of Internal Medicine, Ohio State University Comprehensive Cancer Center, OH, Columbus, United States.
    Berndt, Sonja
    Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, MD, Bethesda, United States.
    Hayes, Richard
    Division of Epidemiology, Department of Population Health, New York University School of Medicine, NY, New York, United States.
    Martinez, Marie Elena
    Population Sciences, Disparities and Community Engagement, University of California San Diego Moores Cancer Center, La Jolla, CA, United States; Department of Family Medicine and Public Health, University of California San Diego, La Jolla, CA, United States.
    Thomas, Sushma
    Fred Hutchinson Cancer Research Center, WA, Seattle, United States.
    Corley, Douglas
    Division of Research, Kaiser Permanente Northern California, CA, Oakland, United States; Department of Gastroenterology, Kaiser Permanente Medical Center, CA, San Francisco, United States.
    Pharoah, Paul
    Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom.
    Larsson, Susanna
    Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Yen, Yun
    Taipei Medical University, Taipei, Taiwan.
    Lenz, Heinz-Josef
    Department of Medicine, Keck School of Medicine, University of Southern California, CA, Los Angeles, United States.
    White, Emily
    Public Health Sciences Division, Fred Hutchinson Cancer Research Center, WA, Seattle, United States; Department of Epidemiology, University of Washington School of Public Health, WA, Seattle, United States.
    Li, Li
    Case Comprehensive Cancer Center, Case Western Reserve University, OH, Cleveland, United States.
    Doheny, Kimberly
    Center for Inherited Disease Research, Department of Genetic Medicine, Johns Hopkins University School of Medicine, MD, Baltimore, United States.
    Pugh, Elizabeth
    Center for Inherited Disease Research, Department of Genetic Medicine, Johns Hopkins University School of Medicine, MD, Baltimore, United States.
    Shelford, Tameka
    Center for Inherited Disease Research, Department of Genetic Medicine, Johns Hopkins University School of Medicine, MD, Baltimore, United States.
    Chan, Andrew
    Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, MA, Boston, United States; Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, MA, Boston, United States; Channing Division of Network Medicine, Brigham and Women’s Hospital and Harvard Medical School, MA, Boston, United States; Broad Institute of Harvard and MIT, MA, Cambridge, United States; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Harvard University, MA, Boston, United States; Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Harvard University, MA, Boston, United States.
    Cruz-Correa, Marcia
    Comprehensive Cancer Center, University of Puerto Rico, San Juan, Puerto Rico.
    Lindblom, Annika
    Department of Clinical Genetics, Karolinska University Hospital, Stockholm, Sweden; Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
    Hunter, David
    Department of Epidemiology, Harvard T.H. Chan School of Public Health, Harvard University, MA, Boston, United States; Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.
    Joshi, Amit
    Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, MA, Boston, United States; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Harvard University, MA, Boston, United States.
    Schafmayer, Clemens
    Department of General Surgery, University Hospital Rostock, Rostock, Germany.
    Scacheri, Peter
    Department of Genetics and Genome Sciences, Case Western Reserve University, OH, Cleveland, United States.
    Kundaje, Anshul
    Department of Genetics, Stanford University, CA, Stanford, United States; Department of Computer Science, Stanford University, CA, Stanford, United States.
    Nickerson, Deborah
    Department of Genome Sciences, University of Washington, WA, Seattle, United States.
    Schoen, Robert
    Department of Medicine and Epidemiology, University of Pittsburgh Medical Center, PA, Pittsburgh, United States.
    Hampe, Jochen
    Department of Medicine I, University Hospital Dresden, Technische Universität Dresden, Dresden, Germany.
    Stadler, Zsofia
    Department of Medicine, Weill Cornell Medical College, NY, New York, United States; Department of Medicine, Memorial Sloan-Kettering Cancer Center, NY, New York, United States.
    Vodicka, Pavel
    Department of Molecular Biology of Cancer, Institute of Experimental Medicine of the Czech Academy of Sciences, Prague, Czech Republic; Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University, Prague, Czech Republic; Faculty of Medicine and Biomedical Center in Pilsen, Charles University, Pilsen, Czech Republic.
    Vodickova, Ludmila
    Department of Molecular Biology of Cancer, Institute of Experimental Medicine of the Czech Academy of Sciences, Prague, Czech Republic; Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University, Prague, Czech Republic; Faculty of Medicine and Biomedical Center in Pilsen, Charles University, Pilsen, Czech Republic.
    Vymetalkova, Veronika
    Department of Molecular Biology of Cancer, Institute of Experimental Medicine of the Czech Academy of Sciences, Prague, Czech Republic; Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University, Prague, Czech Republic; Faculty of Medicine and Biomedical Center in Pilsen, Charles University, Pilsen, Czech Republic.
    Papadopoulos, Nickolas
    Department of Oncology Ludwig Center at the Sidney Kimmel Cancer Center, Johns Hopkins University School of Medicine, MD, Baltimore, United States; Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, MD, Baltimore, United States; Department of Pathology, Johns Hopkins School of Medicine, MD, Baltimore, United States.
    Edlund, Chistopher
    Department of Preventive Medicine, USC Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, CA, Los Angeles, United States.
    Gauderman, William
    Department of Preventive Medicine, USC Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, CA, Los Angeles, United States.
    Thomas, Duncan
    Department of Preventive Medicine, USC Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, CA, Los Angeles, United States.
    Shibata, David
    Department of Surgery, University of Tennessee Health Science Center, TN, Memphis, United States.
    Toland, Amanda
    Departments of Cancer Biology and Genetics and Internal Medicine, Comprehensive Cancer Center, Ohio State University, OH, Columbus, United States.
    Markowitz, Sanford
    Departments of Medicine and Genetics, Case Comprehensive Cancer Center, Case Western Reserve University and University Hospitals of Cleveland, OH, Cleveland, United States.
    Kim, Andre
    Department of Preventive Medicine, USC Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, CA, Los Angeles, United States.
    Chanock, Stephen
    Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, MD, Bethesda, United States.
    van Duijnhoven, Franzel
    Division of Human Nutrition and Health, Wageningen University and Research, Wageningen, Netherlands.
    Feskens, Edith
    Division of Human Nutrition, Wageningen University and Research, Wageningen, Netherlands.
    Sakoda, Lori
    Public Health Sciences Division, Fred Hutchinson Cancer Research Center, WA, Seattle, United States; Division of Research, Kaiser Permanente Northern California, CA, Oakland, United States.
    Gago-Dominguez, Manuela
    Genomic Medicine Group, Galician Public Foundation of Genomic Medicine, Servicio Galego de Saude, Santiago de Compostela, Spain; Instituto de Investigación Sanitaria de Santiago de Compostela, Santiago de Compostela, Spain.
    Wolk, Alicja
    Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Naccarati, Alessio
    Italian Institute for Genomic Medicine, Candiolo Cancer Institute, Turin, Italy; Candiolo Cancer Institute, Candiolo, Italy.
    Pardini, Barbara
    Italian Institute for Genomic Medicine, Candiolo Cancer Institute, Turin, Italy; Candiolo Cancer Institute, Candiolo, Italy.
    FitzGerald, Liesel
    Cancer Epidemiology Division, Cancer Council Victoria, VIC, Melbourne, Australia; Menzies Institute for Medical Research, University of Tasmania, TAS, Hobart, Australia.
    Lee, Soo Chin
    National University Cancer Institute, Singapore, Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.
    Ogino, Shuji
    Department of Epidemiology, Harvard T.H. Chan School of Public Health, Harvard University, MA, Boston, United States; Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, MA, Boston, United States; Cancer Immunology Program, Dana-Farber Harvard Cancer Center, MA, Boston, United States; Broad Institute of MIT and Harvard, MA, Cambridge, United States.
    Bien, Stephanie
    Public Health Sciences Division, Fred Hutchinson Cancer Research Center, WA, Seattle, United States.
    Kooperberg, Charles
    Public Health Sciences Division, Fred Hutchinson Cancer Research Center, WA, Seattle, United States.
    Li, Christopher
    Public Health Sciences Division, Fred Hutchinson Cancer Research Center, WA, Seattle, United States.
    Lin, Yi
    Public Health Sciences Division, Fred Hutchinson Cancer Research Center, WA, Seattle, United States.
    Prentice, Ross
    Public Health Sciences Division, Fred Hutchinson Cancer Research Center, WA, Seattle, United States; Department of Biostatistics, University of Washington, WA, Seattle, United States.
    Qu, Conghui
    Public Health Sciences Division, Fred Hutchinson Cancer Research Center, WA, Seattle, United States.
    Bézieau, Stéphane
    Service de Génétique Médicale, Centre Hospitalier Universitaire Nantes, Nantes, France.
    Tangen, Catherine
    SWOG Statistical Center, Fred Hutchinson Cancer Research Center, WA, Seattle, United States.
    Mardis, Elaine
    Department of Pediatrics, Nationwide Children’s Hospital, The Steve and Cindy Rasmussen Institute for Genomic Medicine, OH, Columbus, United States.
    Yamaji, Taiki
    Division of Epidemiology, National Cancer Center Institute for Cancer Control, National Cancer Center, Tokyo, Japan.
    Sawada, Norie
    Division of Cohort Research, National Cancer Center Institute for Cancer Control, National Cancer Center, Tokyo, Japan.
    Iwasaki, Motoki
    Division of Epidemiology, National Cancer Center Institute for Cancer Control, National Cancer Center, Tokyo, Japan; Division of Cohort Research, National Cancer Center Institute for Cancer Control, National Cancer Center, Tokyo, Japan.
    Haiman, Christopher
    Department of Preventive Medicine, Center for Genetic Epidemiology, University of Southern California, CA, Los Angeles, United States.
    Le Marchand, Loic
    Cancer Center, University of Hawaii, HI, Honolulu, United States.
    Wu, Anna
    Preventative Medicine, University of Southern California, CA, Los Angeles, United States.
    Qu, Chenxu
    USC Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, CA, Los Angeles, United States.
    McNeil, Caroline
    USC Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, CA, Los Angeles, United States.
    Coetzee, Gerhard
    Van Andel Research Institute, MI, Grand Rapids, United States.
    Hayward, Caroline
    MRC Human Genetics Unit, Institute of Genomics and Cancer, University of Edinburgh, Edinburgh, United Kingdom.
    Deary, Ian
    Lothian Birth Cohorts group, Department of Psychology, University of Edinburgh, Edinburgh, United Kingdom.
    Harris, Sarah
    Lothian Birth Cohorts group, Department of Psychology, University of Edinburgh, Edinburgh, United Kingdom.
    Theodoratou, Evropi
    Centre for Global Health, Usher Institute, University of Edinburgh, Edinburgh, United Kingdom.
    Reid, Stuart
    Colon Cancer Genetics Group, Medical Research Council Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, United Kingdom.
    Walker, Marion
    Colon Cancer Genetics Group, Medical Research Council Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, United Kingdom.
    Ooi, Li Yin
    Colon Cancer Genetics Group, Medical Research Council Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, United Kingdom; Department of Pathology, National University Hospital, National University Health System, Singapore, Singapore.
    Moreno, Victor
    Colorectal Cancer Group, ONCOBELL Program, Bellvitge Biomedical Research Institute, Barcelona, Spain; Oncology Data Analytics Program, Catalan Institute of Oncology, Barcelona, Spain; Consortium for Biomedical Research in Epidemiology and Public Health, Madrid, Madrid, Spain; Department of Clinical Sciences, Faculty of Medicine, University of Barcelona, Barcelona, Spain.
    Casey, Graham
    Center for Public Health Genomics, Department of Public Health Sciences, University of Virginia, VA, Charlottesville, United States.
    Gruber, Stephen
    Department of Medical Oncology and Center For Precision Medicine, City of Hope National Medical Center, CA, Duarte, United States.
    Tomlinson, Ian
    Edinburgh Cancer Research Centre, Institute of Genomics and Cancer, University of Edinburgh, Edinburgh, United Kingdom; Institute of Cancer and Genomic Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom.
    Zheng, Wei
    Division of Epidemiology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt Epidemiology Center, Vanderbilt University Medical Center, TN, Nashville, United States.
    Dunlop, Malcolm
    Colon Cancer Genetics Group, Medical Research Council Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, United Kingdom.
    Houlston, Richard
    Division of Genetics and Epidemiology, Institute of Cancer Research, London, United Kingdom.
    Peters, Ulrike
    Public Health Sciences Division, Fred Hutchinson Cancer Research Center, WA, Seattle, United States; Department of Epidemiology, University of Washington, WA, Seattle, United States.
    Deciphering colorectal cancer genetics through multi-omic analysis of 100,204 cases and 154,587 controls of European and east Asian ancestries2023Ingår i: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 55, s. 89-99Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Colorectal cancer (CRC) is a leading cause of mortality worldwide. We conducted a genome-wide association study meta-analysis of 100,204 CRC cases and 154,587 controls of European and east Asian ancestry, identifying 205 independent risk associations, of which 50 were unreported. We performed integrative genomic, transcriptomic and methylomic analyses across large bowel mucosa and other tissues. Transcriptome- and methylome-wide association studies revealed an additional 53 risk associations. We identified 155 high-confidence effector genes functionally linked to CRC risk, many of which had no previously established role in CRC. These have multiple different functions and specifically indicate that variation in normal colorectal homeostasis, proliferation, cell adhesion, migration, immunity and microbial interactions determines CRC risk. Crosstissue analyses indicated that over a third of effector genes most probably act outside the colonic mucosa. Our findings provide insights into colorectal oncogenesis and highlight potential targets across tissues for new CRC treatment and chemoprevention strategies.

  • 36. Ferrari, Pietro
    et al.
    Jenab, Mazda
    Norat, Teresa
    Moskal, Aurelie
    Slimani, Nadia
    Olsen, Anja
    Tjønneland, Anne
    Overvad, Kim
    Jensen, Majken K
    Boutron-Ruault, Marie-Christine
    Clavel-Chapelon, Françoise
    Morois, Sophie
    Rohrmann, Sabine
    Linseisen, Jakob
    Boeing, Heiner
    Bergmann, Manuela
    Kontopoulou, Dimitra
    Trichopoulou, Antonia
    Kassapa, Christina
    Masala, Giovanna
    Krogh, Vittorio
    Vineis, Paolo
    Panico, Salvatore
    Tumino, Rosario
    van Gils, Carla H
    Peeters, Petra
    Bueno-de-Mesquita, H Bas
    Ocké, Marga C
    Skeie, Guri
    Lund, Eiliv
    Agudo, Antonio
    Ardanaz, Eva
    López, Dolores C
    Sanchez, Maria-Jose
    Quirós, José R
    Amiano, Pilar
    Berglund, Göran
    Manjer, Jonas
    Palmqvist, Richard
    Umeå universitet, Medicinsk fakultet, Medicinsk biovetenskap, Patologi.
    Van Guelpen, Bethany
    Umeå universitet, Medicinsk fakultet, Medicinsk biovetenskap, Patologi.
    Allen, Naomi
    Key, Tim
    Bingham, Sheila
    Mazuir, Mathieu
    Boffetta, Paolo
    Kaaks, Rudolf
    Riboli, Elio
    Lifetime and baseline alcohol intake and risk of colon and rectal cancers in the European prospective investigation into cancer and nutrition (EPIC).2007Ingår i: Int J Cancer, ISSN 0020-7136, Vol. 121, nr 9, s. 2065-72Artikel i tidskrift (Refereegranskat)
  • 37.
    Guo, Xingyi
    et al.
    Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, and Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, TN, Nashville, United States.
    Lin, Weiqiang
    The Kidney Disease Center, the First Affiliated Hospital, Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, China.
    Wen, Wanqing
    Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, and Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, TN, Nashville, United States.
    Huyghe, Jeroen
    Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, WA, Seattle, United States.
    Bien, Stephanie
    Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, WA, Seattle, United States.
    Cai, Qiuyin
    Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, and Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, TN, Nashville, United States.
    Harrison, Tabitha
    Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, WA, Seattle, United States.
    Chen, Zhishan
    Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, and Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, TN, Nashville, United States.
    Qu, Conghui
    Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, WA, Seattle, United States.
    Bao, Jiandong
    Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, and Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, TN, Nashville, United States.
    Long, Jirong
    Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, and Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, TN, Nashville, United States.
    Yuan, Yuan
    The Kidney Disease Center, the First Affiliated Hospital, Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, China.
    Wang, Fangqin
    The Kidney Disease Center, the First Affiliated Hospital, Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, China.
    Bai, Mengqiu
    The Kidney Disease Center, the First Affiliated Hospital, Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, China.
    Abecasis, Goncalo R.
    Department of Biostatistics and Center for Statistical Genetics, University of Michigan, MI, Ann Arbor, United States.
    Albanes, Demetrius
    Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, MD, Bethesda, United States.
    Berndt, Sonja I.
    Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, MD, Bethesda, United States.
    Bézieau, Stéphane
    Service de Génétique Médicale, Centre Hospitalier Universitaire, Nantes, France.
    Bishop, D. Timothy
    Leeds Institute of Cancer and Pathology, University of Leeds, Leeds, United Kingdom.
    Brenner, Hermann
    Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany; Division of Preventive Oncology, German Cancer Research Center and National Center for Tumor Diseases, Heidelberg, Germany.
    Buch, Stephan
    Department of Medicine I, University Hospital Dresden, Technische Universität Dresden, Dresden, Germany.
    Burnett-Hartman, Andrea
    Institute for Health Research, Kaiser Permanente Colorado, CO, Denver, United States.
    Campbell, Peter T.
    Behavioral and Epidemiology Research Group, American Cancer Society, Georgia, Atlanta, Georgia.
    Castellví-Bel, Sergi
    Gastroenterology Department, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, University of Barcelona, Barcelona, Spain.
    Chan, Andrew T.
    Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, MA, Boston, United States; Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, MA, Boston, United States.
    Chang-Claude, Jenny
    Division of Cancer Epidemiology, German Cancer Research Center, Heidelberg, Germany; University Medical Centre Hamburg-Eppendorf, University Cancer Centre Hamburg, Hamburg, Germany.
    Chanock, Stephen J.
    Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, MD, Bethesda, United States.
    Cho, Sang Hee
    Department of Hematology-Oncology, Chonnam National University Hospital, Hwasun, South Korea.
    Conti, David V.
    Department of Preventive Medicine and University of Southern California Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, CA, Los Angeles, United States.
    Chapelle, Albert de la
    Department of Cancer Biology and Genetics and the Comprehensive Cancer Center, The Ohio State University, OH, Columbus, United States.
    Feskens, Edith J.M.
    Division of Human Nutrition and Health, Wageningen University and Research, Wageningen, Netherlands.
    Gallinger, Steven J.
    Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, ON, Toronto, Canada.
    Giles, Graham G.
    Cancer Epidemiology Division, Cancer Council Victoria, Victoria, Melbourne, Australia; Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Victoria, Melbourne, Australia.
    Goodman, Phyllis J.
    SWOG Statistical Center, Fred Hutchinson Cancer Research Center, WA, Seattle, United States.
    Gsur, Andrea
    Institute of Cancer Research, Department of Medicine I, Medical University Vienna, Vienna, Austria.
    Guinter, Mark
    Behavioral and Epidemiology Research Group, American Cancer Society, Georgia, Atlanta, Georgia.
    Gunter, Marc J.
    Nutrition and Metabolism Section, International Agency for Research on Cancer, World Health Organization, Lyon, France.
    Hampe, Jochen
    Department of Medicine I, University Hospital Dresden, Technische Universität Dresden, Dresden, Germany.
    Hampel, Heather
    Division of Human Genetics, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center, OH, Columbus, United States.
    Hayes, Richard B.
    Division of Epidemiology, Department of Population Health, New York University School of Medicine, NY, New York, United States.
    Hoffmeister, Michael
    Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany.
    Kampman, Ellen
    Division of Human Nutrition and Health, Wageningen University and Research, Wageningen, Netherlands.
    Kang, Hyun Min
    Department of Biostatistics and Center for Statistical Genetics, University of Michigan, MI, Ann Arbor, United States.
    Keku, Temitope O.
    Center for Gastrointestinal Biology and Disease, University of North Carolina, NC, Chapel Hill, United States.
    Kim, Hyeong Rok
    Department of Surgery, Chonnam National University Hwasun Hospital and Medical School, Korea, Hwasun, South Korea.
    Le Marchand, Loic
    University of Hawaii Cancer Center, HI, Honolulu, United States.
    Lee, Soo Chin
    National University Cancer Institute, Singapore; Cancer Science Institute of Singapore, National University of Singapore, Singapore.
    Li, Christopher I.
    Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, WA, Seattle, United States.
    Li, Li
    Department of Family Medicine, University of Virginia, VA, Charlottesville, United States.
    Lindblom, Annika
    Department of Clinical Genetics, Karolinska University Hospital, Stockholm, Sweden; Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
    Lindor, Noralane
    Health Sciences Research, Mayo Clinic, AZ, Scottsdale, United States.
    Milne, Roger L.
    Cancer Epidemiology Division, Cancer Council Victoria, Victoria, Melbourne, Australia; Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Victoria, Melbourne, Australia.
    Moreno, Victor
    Oncology Data Analytics Program, Catalan Institute of Oncology-IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain; CIBER Epidemiología y Salud Pública, Madrid, Spain.
    Murphy, Neil
    Behavioral and Epidemiology Research Group, American Cancer Society, Georgia, Atlanta, Georgia.
    Newcomb, Polly A.
    Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, WA, Seattle, United States; School of Public Health, University of Washington, WA, Seattle, United States.
    Nickerson, Deborah A.
    Department of Genome Sciences, University of Washington, WA, Seattle, United States.
    Offit, Kenneth
    Clinical Genetics Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, NY, New York, United States; Department of Medicine, Weill Cornell Medical College, NY, New York, United States.
    Pearlman, Rachel
    Division of Human Genetics, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center, OH, Columbus, United States.
    Pharoah, Paul D.P.
    Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom.
    Platz, Elizabeth A.
    Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, MD, Baltimore, United States.
    Potter, John D.
    Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, WA, Seattle, United States.
    Rennert, Gad
    Department of Community Medicine and Epidemiology, Lady Davis Carmel Medical Center, Haifa, Israel; Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
    Sakoda, Lori C.
    Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, WA, Seattle, United States; Division of Research, Kaiser Permanente Northern California, CA, Oakland, United States.
    Schafmayer, Clemens
    Department of General Surgery, University Hospital Rostock, Rostock, Germany.
    Schmit, Stephanie L.
    Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center and Research Institute, FL, Tampa, United States.
    Schoen, Robert E.
    Department of Medicine and Epidemiology, University of Pittsburgh Medical Center, PA, Pittsburgh, United States.
    Schumacher, Fredrick R.
    Department of Population and Quantitative Health Sciences, Case Western Reserve University, OH, Cleveland, United States.
    Slattery, Martha L.
    Department of Internal Medicine, University of Utah, UT, Salt Lake City, United States.
    Su, Yu-Ru
    Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, WA, Seattle, United States.
    Tangen, Catherine M.
    SWOG Statistical Center, Fred Hutchinson Cancer Research Center, WA, Seattle, United States.
    Ulrich, Cornelia M.
    Huntsman Cancer Institute and Department of Population Health Sciences, University of Utah, UT, Salt Lake City, United States.
    van Duijnhoven, Franzel J.B.
    Division of Human Nutrition and Health, Wageningen University and Research, Wageningen, Netherlands.
    van Guelpen, Bethany
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Visvanathan, Kala
    Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, MD, Baltimore, United States.
    Vodicka, Pavel
    Department of Molecular Biology of Cancer, Institute of Experimental Medicine of the Czech Academy of Sciences, Prague, Czech Republic; Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University, Prague, Czech Republic.
    Vodickova, Ludmila
    Department of Molecular Biology of Cancer, Institute of Experimental Medicine of the Czech Academy of Sciences, Prague, Czech Republic; Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University, Prague, Czech Republic.
    Vymetalkova, Veronika
    Department of Molecular Biology of Cancer, Institute of Experimental Medicine of the Czech Academy of Sciences, Prague, Czech Republic; Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University, Prague, Czech Republic.
    Wang, Xiaoliang
    Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, WA, Seattle, United States.
    White, Emily
    Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, WA, Seattle, United States; Department of Epidemiology, University of Washington School of Public Health, WA, Seattle, United States.
    Wolk, Alicja
    Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Woods, Michael O.
    Memorial University of Newfoundland, Discipline of Genetics, St John's, NL, Canada.
    Casey, Graham
    Center for Public Health Genomics, University of Virginia, VA, Charlottesville, United States.
    Hsu, Li
    Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, WA, Seattle, United States.
    Jenkins, Mark A.
    Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Victoria, Melbourne, Australia.
    Gruber, Stephen B.
    Department of Preventive Medicine and University of Southern California Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, CA, Los Angeles, United States.
    Peters, Ulrike
    Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, WA, Seattle, United States; Department of Epidemiology, University of Washington School of Public Health, WA, Seattle, United States.
    Zheng, Wei
    Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, and Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, TN, Nashville, United States.
    Identifying Novel Susceptibility Genes for Colorectal Cancer Risk From a Transcriptome-Wide Association Study of 125,478 Subjects2021Ingår i: Gastroenterology, ISSN 0016-5085, E-ISSN 1528-0012, Vol. 160, nr 4, s. 1164-1178Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background And Aims: Susceptibility genes and the underlying mechanisms for the majority of risk loci identified by genome-wide association studies (GWAS) for colorectal cancer (CRC) risk remain largely unknown. We conducted a transcriptome-wide association study (TWAS) to identify putative susceptibility genes.

    Methods: Gene-expression prediction models were built using transcriptome and genetic data from the 284 normal transverse colon tissues of European descendants from the Genotype-Tissue Expression (GTEx), and model performance was evaluated using data from The Cancer Genome Atlas (n = 355). We applied the gene-expression prediction models and GWAS data to evaluate associations of genetically predicted gene-expression with CRC risk in 58,131 CRC cases and 67,347 controls of European ancestry. Dual-luciferase reporter assays and knockdown experiments in CRC cells and tumor xenografts were conducted.

    Results: We identified 25 genes associated with CRC risk at a Bonferroni-corrected threshold of P < 9.1 × 10–6, including genes in 4 novel loci, PYGL (14q22.1), RPL28 (19q13.42), CAPN12 (19q13.2), MYH7B (20q11.22), and MAP1L3CA (20q11.22). In 9 known GWAS-identified loci, we uncovered 9 genes that have not been reported previously, whereas 4 genes remained statistically significant after adjusting for the lead risk variant of the locus. Through colocalization analysis in GWAS loci, we additionally identified 12 putative susceptibility genes that were supported by TWAS analysis at P <.01. We showed that risk allele of the lead risk variant rs1741640 affected the promoter activity of CABLES2. Knockdown experiments confirmed that CABLES2 plays a vital role in colorectal carcinogenesis.

    Conclusions: Our study reveals new putative susceptibility genes and provides new insight into the biological mechanisms underlying CRC development.

  • 38.
    Gylling, Björn
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Myte, Robin
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Schneede, Jørn
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Farmakologi.
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning.
    Häggstrom, Jenny
    Umeå universitet, Samhällsvetenskapliga fakulteten, Handelshögskolan vid Umeå universitet, Statistik.
    Johansson, Ingegerd
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    Ulvik, Arve
    Ueland, Per M.
    Van Guelpen, Bethany
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Palmqvist, Richard
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Vitamin B-6 and colorectal cancer risk: a prospective population-based study using 3 distinct plasma markers of vitamin B-6 status2017Ingår i: American Journal of Clinical Nutrition, ISSN 0002-9165, E-ISSN 1938-3207, Vol. 105, nr 4, s. 897-904Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Higher plasma concentrations of the vitamin B-6 marker pyridoxal 5#-phosphate (PLP) have been associated with reduced colorectal cancer (CRC) risk. Inflammatory processes, including vitamin B-6 catabolism, could explain such findings. Objective: We investigated 3 biomarkers of vitamin B-6 status in relation to CRC risk. Design: This was a prospective case-control study of 613 CRC cases and 1190 matched controls nested within the Northern Sweden Health and Disease Study (n = 114,679). Participants were followed from 1985 to 2009, and the median follow-up from baseline to CRC diagnosis was 8.2 y. PLP, pyridoxal, pyridoxic acid (PA), 3-hydroxykynurenine, and xanthurenic acids (XAs) were measured in plasma with the use of liquid chromatography-tandem mass spectrometry. We calculated relative and absolute risks of CRC for PLP and the ratios 3-hydroxykynurenine: XA (HK: XA), an inverse marker of functional vitamin B-6 status, and PA:(PLP + pyridoxal) (PAr), a marker of inflammation and oxidative stress and an inverse marker of vitamin B-6 status. Results: Plasma PLP concentrations were associated with a reduced CRC risk for the third compared with the first quartile and for PLP sufficiency compared with deficiency [OR: 0.60 (95% CI: 0.44, 0.81) and OR: 0.55 (95% CI: 0.37, 0.81), respectively]. HK: XA and PAr were both associated with increased CRC risk [OR: 1.48 (95% CI: 1.08, 2.02) and OR: 1.50 (95% CI: 1.10, 2.04), respectively] for the fourth compared with the first quartile. For HK: XA and PAr, the findings were mainly observed in study participants with,10.5 y of follow-up between sampling and diagnosis. Conclusions: Vitamin B-6 deficiency as measured by plasma PLP is associated with a clear increase in CRC risk. Furthermore, our analyses of novel markers of functional vitamin B-6 status and vitamin B-6-associated oxidative stress and inflammation suggest a role in tumor progression rather than initiation.

  • 39.
    Gylling, Björn
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Myte, Robin
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Ulvik, Arve
    Bevital AS, Laboratory building, Bergen, Norway.
    Ueland, Per Magne
    Department of Clinical Science, University of Bergen and Laboratory of Clinical Biochemistry, Haukeland University Hospital, Bergen, Norway.
    Midttun, Øivind
    Bevital AS, Laboratory building, Bergen, Norway.
    Schneede, Jørn
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Farmakologi.
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Häggström, Jenny
    Umeå universitet, Samhällsvetenskapliga fakulteten, Handelshögskolan vid Umeå universitet, Statistik.
    Johansson, Ingegerd
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    van Guelpen, Bethany
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Palmqvist, Richard
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    One-carbon metabolite ratios as functional B-vitamin markers and in relation to colorectal cancer risk2019Ingår i: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 144, nr 5, s. 68s. 947-956Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: One-carbon metabolism biomarker are easily measured in plasma, but analyzing them one at a time in relation to disease does not take into account the interdependence of the many factors involved. The relative dynamics of major one-carbon metabolism branches can be assessed by relating the functional B-vitamin marker total homocysteine (tHcy) to transsulfuration (total cysteine) and methylation (creatinine) outputs.

    Objective: We validated the ratios of tHcy to total cysteine (Hcy:Cys), tHcy to creatinine (Hcy:Cre), and tHcy to cysteine to creatinine (Hcy:Cys:Cre) as functional markers of B-vitamin status. We also calculated the associations of these ratios to colorectal cancer (CRC) risk.

    Design: The relative contribution of potential confounders to the variance of the ratio-based B-vitamin markers was calculated by linear regression in a nested case-control study of 613 CRC cases and 1211 matched controls. Total B-vitamin status was represented by a summary score comprising Z-standardized plasma concentrations of folate, cobalamin, betaine, pyridoxal 5´-phosphate, and riboflavin. Associations with CRC risk were estimated using conditional logistic regression.

    Results: The ratio-based B-vitamin markers all outperformed tHcy as markers of total B-vitamin status, in both CRC cases and controls. Associations with CRC risk were similar for the ratio-based B-vitamin markers and total B-vitamin status (approximately 25% lower risk for high versus low B-vitamin status).

    Conclusions: Ratio-based B-vitamin markers were good predictors of total B-vitamin status, and displayed similar associations with CRC risk. Since tHcy and creatinine are routinely clinically analyzed, Hcy:Cre could be easily implemented in clinical practice to aid interpretation of tHcy results.

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  • 40.
    Gylling, Björn
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Van Guelpen, Bethany
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Schneede, Jörn
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Farmakologi.
    Hultdin, Johan
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Ueland, Per Magne
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning. Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning.
    Johansson, Ingegerd
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    Palmqvist, Richard
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Low folate levels are associated with reduced risk of colorectal cancer in a population with low folate status2014Ingår i: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 23, nr 10, s. 2136-2144Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: A diet rich in folate is associated with a reduced colorectal cancer risk, whereas the role of circulating levels is less clear. The aim of this study was to relate prediagnostic plasma folate, vitamin B12, and homocysteine concentrations to the risk of colorectal cancer.

    METHODS: This was a prospective case-control study of 331 cases and 662 matched controls nested within the population-based Northern Sweden Health and Disease Study. Median follow-up time from recruitment to diagnosis was 10.8 years.

    RESULTS: Plasma folate concentrations were positively related to colorectal cancer risk; multivariate odds ratios were 1.62 [95% confidence intervals (CI), 1.08-2.42] and 1.42 (95% CI, 0.94-2.21) for the middle and highest versus lowest tertile, respectively. In subjects with follow-up <10.8 years, a statistically significant doubled risk was observed for the middle and highest versus lowest tertile, whereas findings for longer follow-up times were null. A positive risk relationship was also observed for tumor stage III-IV but not I-II. Plasma vitamin B12 concentrations were inversely associated with rectal cancer risk. Homocysteine was not significantly related to colorectal cancer risk.

    CONCLUSIONS: In this population-based, nested case-control study, low plasma folate concentrations were associated with a reduced colorectal cancer risk. This protective role was mainly observed in subjects with higher tumor stage or shorter follow-up time between recruitment and diagnosis. Low circulating folate status may protect against colorectal cancer or suppress progression of preneoplastic or neoplastic lesions.

    IMPACT: These findings may have relevance for the ongoing debate about mandatory folic acid fortification of flour.

  • 41.
    Hadrévi, Jenny
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Myte, Robin
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Olsson, Tommy
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Palmqvist, Richard
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Slunga-Järvholm, Lisbeth
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för hållbar hälsa.
    van Guelpen, Bethany
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Work-Related Stress Was Not Associated with Increased Cancer Risk in a Population-Based Cohort Setting2021Ingår i: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 31, nr 1, s. 51-57Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Stress is a commonly perceived cause of cancer, but the evidence to date is limited and inconclusive. We examined work-related stress in relation to cancer incidence in a population-based cohort, with outcome data from Swedish national registries.

    Methods: The study population included 113,057 participants in the Västerbotten Intervention Programme. HRs were estimated using Cox proportional hazards regression, for cancer overall and for types with ≥500 cases, and adjusting for several potential confounders. The primary exposure was prediagnostic work-related stress, using the well established Karasek job demand/control model. Demand and control variables were dichotomized at the median, and participants were classified according to combinations of these categories. We also considered social network and aspects of quality of life.

    Results: "High-strain" work (high demand/low control) was not associated with cancer risk compared with "low-strain" work (low demand/high control): multivariable HR 1.01 [95% confidence interval (CI), 0.94-1.08] for men and 0.99 (95% CI, 0.92-1.07) for women. Results were also null for most cancer types assessed: prostate, breast, colorectal, lung, and gastrointestinal (GI). The risk of GI cancer was lower for "passive" (low demand/low control) versus "low-strain" work, particularly for colorectal cancer in women: multivariable HR 0.71 (95% CI, 0.55-0.91), but statistical significance was lost after adjustment for multiple testing.

    Conclusions: The findings of this population-based, cohort study do not support a role for work-related stress in determining cancer risk.

    Impact: This study helps fill an important knowledge gap given the common concern about stress as a risk factor for cancer.

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  • 42.
    Harbs, Justin
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Rentoft, Matilda
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi. Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik. Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Melin, Beatrice S.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Gylling, Björn
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Palmqvist, Richard
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Harlid, Sophia
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    van Guelpen, Bethany
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper. Umeå universitet, Medicinska fakulteten, Wallenberg centrum för molekylär medicin vid Umeå universitet (WCMM).
    Identifying prediagnostic colorectal cancer biomarkers using a targeted proteomics platform with extensive coverageManuskript (preprint) (Övrigt vetenskapligt)
  • 43.
    Harbs, Justin
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Rinaldi, Sabina
    International Agency for Research on Cancer, World Health Organization, Lyon, France.
    Gicquiau, Audrey
    International Agency for Research on Cancer, World Health Organization, Lyon, France.
    Keski-Rahkonen, Pekka
    International Agency for Research on Cancer, World Health Organization, Lyon, France.
    Mori, Nagisa
    International Agency for Research on Cancer, World Health Organization, Lyon, France.
    Liu, Xijia
    Umeå universitet, Samhällsvetenskapliga fakulteten, Handelshögskolan vid Umeå universitet, Statistik.
    Kaaks, Rudolf
    Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
    Katzke, Verena
    Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
    Schulze, Matthias B.
    Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany; Institute of Nutritional Science, University of Potsdam, Potsdam, Germany.
    Agnoli, Claudia
    Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy.
    Tumino, Rosario
    Cancer Registry and Histopathology Department, Provincial Health Authority (ASP 7), Ragusa, Italy.
    Bueno-De-Mesquita, Bas
    Centre for Nutrition, Prevention and Health Services, National Institute for Public Health and the Environment (RIVM), Bilthoven, Netherlands.
    Crous-Bou, Marta
    Unit of Nutrition and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology (ICO), Bellvitge Biomedical Research Institute (IDIBELL), L’Hospitalet de Llobregat, Barcelona, Spain; Department of Epidemiology, Harvard T.H. Chan School of Public Health, MA, Boston, United States.
    Sánchez, Maria-Jose
    Escuela Andaluza de Salud Pública (EASP), Granada, Spain; Instituto de Investigación Biosanitaria ibs.GRANADA, Granada, Spain; Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain; Department of Preventive Medicine and Public Health, University of Granada, Granada, Spain.
    Aizpurua, Amaia
    Ministry of Health of the Basque Government, Sub-Directorate for Public Health and Addictions of Gipuzkoa, San Sebastián, Spain.
    Chirlaque, María-Dolores
    Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain; Department of Epidemiology, Regional Health Council, IMIB-Arrixaca, Murcia University, Murcia, Spain.
    Gurrea, Aurelio Barricarte
    Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain; Navarra Public Health Institute, Pamplona, Spain; Navarra Institute for Health Research (IdiSNA), Pamplona, Spain.
    Travis, Ruth C.
    Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.
    Watts, Eleanor L.
    Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.
    Christakoudi, Sofia
    Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom; MRC Centre for Transplantation, Division of Transplantation Immunology and Mucosal Biology, Faculty of Life Sciences & Medicine, King’s College London, London, United Kingdom.
    Tsilidis, Konstantinos K.
    Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom; Department of Hygiene and Epidemiology, Faculty of Medicine, University of Ioannina School of Medicine, Ioannina, Greece.
    Weiderpass, Elisabete
    International Agency for Research on Cancer, World Health Organization, Lyon, France.
    Gunter, Marc J.
    International Agency for Research on Cancer, World Health Organization, Lyon, France.
    van Guelpen, Bethany
    Umeå universitet, Medicinska fakulteten, Wallenberg centrum för molekylär medicin vid Umeå universitet (WCMM). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Murphy, Neil
    International Agency for Research on Cancer, World Health Organization, Lyon, France.
    Harlid, Sophia
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Circulating Sex Hormone Levels and Colon Cancer Risk in Men: A Nested Case–Control Study and Meta-Analysis2022Ingår i: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 31, nr 4, s. 793-803Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Endogenous sex hormones may contribute to higher colorectal cancer incidence rates in men compared with women, but despite an increased number of studies, clear evidence is lacking.

    Methods: We conducted a comprehensive nested case–control study of circulating concentrations of sex hormones, sex hormone precursors, and sex hormone binding globulin (SHBG) in relation to subsequent colon cancer risk in European men. Concentrations were measured using liquid LC/MS-MS in prospectively collected plasma samples from 690 cases and 690 matched controls from the European Prospective Investigation into Cancer and Nutrition (EPIC) and the Northern Sweden Health and Disease Study (NSHDS) cohorts. Multivariable conditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI). In addition, we conducted a meta-analysis of previous studies on men.

    Results: Circulating levels of testosterone (OR, 0.68; 95% CI, 0.51–0.89) and SHBG (OR, 0.77; 95% CI, 0.62–0.96) were inversely associated with colon cancer risk. For free testosterone, there was a nonsignificant inverse association (OR, 0.83; 95% CI, 0.58–1.18). In a dose–response meta-analysis of endogenous sex hormone levels, inverse associations with colorectal/colon cancer risk were found for testosterone [relative risks (RR) per 100 ng/dL ¼ 0.98; 95% CI, 0.96–1.00; I2 ¼ 22%] and free testosterone (RR per 1 ng/dL ¼ 0.98; 95% CI, 0.95–1.00; I2 ¼ 0%).

    Conclusions: Our results provide suggestive evidence for the association between testosterone, SHBG, and male colon cancer development.

    Impact: Additional support for the involvement of sex hormones in male colon cancer.

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  • 44.
    Harbs, Justin
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Rinaldi, Sabina
    International Agency for Research on Cancer, World Health Organization, Lyon, France.
    Keski-Rahkonen, Pekka
    International Agency for Research on Cancer, World Health Organization, Lyon, France.
    Liu, Xijia
    Umeå universitet, Samhällsvetenskapliga fakulteten, Handelshögskolan vid Umeå universitet, Statistik.
    Palmqvist, Richard
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    van Guelpen, Bethany
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi. Umeå universitet, Medicinska fakulteten, Wallenberg centrum för molekylär medicin vid Umeå universitet (WCMM).
    Harlid, Sophia
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    An epigenome-wide analysis of sex hormone levels and DNA methylation in male blood samples2023Ingår i: Epigenetics, ISSN 1559-2294, E-ISSN 1559-2308, Vol. 18, nr 1, artikel-id 2196759Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Endogenous sex hormones and DNA methylation both play important roles in various diseases. However, their interplay is largely unknown. A deeper understanding of their interrelationships could provide new insights into the pathology of disease development. We, therefore, investigated associations between circulating sex hormones, sex hormone binding globulin (SHBG), and DNA methylation in blood, using samples from 77 men (65 with repeated samples), from the population-based Northern Sweden Health and Disease Study (NSHDS). DNA methylation was measured in buffy coat using the Infinium Methylation EPIC BeadChip (Illumina). Sex hormone (oestradiol, oestrone, testosterone, androstenedione, dehydroepiandrosterone, and progesterone) and SHBG concentrations were measured in plasma using a high-performance liquid chromatography tandem mass spectrometry (LC/MS-MS) method and an enzyme-linked immunoassay, respectively. Associations between sex hormones, SHBG, and DNA methylation were estimated using both linear regression and mixed-effects models. Additionally, we used the comb-p method to identify differentially methylated regions based on nearby P values. We identified one novel CpG site (cg14319657), at which DNA methylation was associated with dehydroepiandrosterone, surpassing a genome-wide significance level. In addition, more than 40 differentially methylated regions were associated with levels of sex hormones and SHBG and several of these mapped to genes involved in hormone-related diseases. Our findings support a relationship between circulating sex hormones and DNA methylation and suggest that further investigation is warranted, both for validation, further exploration and to gain a deeper understanding of the mechanisms and potential consequences for health and disease.

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  • 45.
    Harewood, Rhea
    et al.
    International Agency for Research on Cancer (IARC), 25 Av. Tony Garnier, Lyon, France.
    Rothwell, Joseph A.
    Centre for Epidemiology and Population Health (U1018), Exposome and Heredity Team, Faculté de Médecine, Université Paris-Saclay, UVSQ, INSERM, Gustave Roussy, Villejuif, France.
    Bešević, Jelena
    Clinical Trial Service Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.
    Viallon, Vivian
    International Agency for Research on Cancer (IARC), 25 Av. Tony Garnier, Lyon, France.
    Achaintre, David
    International Agency for Research on Cancer (IARC), 25 Av. Tony Garnier, Lyon, France; School of Plant Sciences and Food Security, Faculty of Biology, Tel-Aviv University, Tel Aviv-Yafo, Israel.
    Gicquiau, Audrey
    International Agency for Research on Cancer (IARC), 25 Av. Tony Garnier, Lyon, France.
    Rinaldi, Sabina
    International Agency for Research on Cancer (IARC), 25 Av. Tony Garnier, Lyon, France.
    Wedekind, Roland
    International Agency for Research on Cancer (IARC), 25 Av. Tony Garnier, Lyon, France.
    Prehn, Cornelia
    Metabolomics and Proteomics Core, Helmholtz Zentrum München, Neuherberg, Germany.
    Adamski, Jerzy
    Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, 8 Medical Drive, Singapore, South Africa; Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, Ingolstädter Landstraße 1, Neuherberg, Germany; Institute of Biochemistry, Faculty of Medicine, University of Ljubljana, Vrazov trg 2, Ljubljana, Slovenia.
    Schmidt, Julie A.
    Department of Clinical Medicine, Department of Clinical Epidemiology, Aarhus University and Aarhus University Hospital, Olof Palmes Allé 43-45, Aarhus N, Denmark.
    Jacobs, Inarie
    International Agency for Research on Cancer (IARC), 25 Av. Tony Garnier, Lyon, France.
    Tjønneland, Anne
    Danish Cancer Society Research Center, Diet, Cancer and Health, Strandboulevarden 49, Copenhagen, Denmark; Department of Public Health, University of Copenhagen, Copenhagen, Denmark.
    Olsen, Anja
    Danish Cancer Society Research Center, Diet, Cancer and Health, Strandboulevarden 49, Copenhagen, Denmark; The Department of Public Health, University of Aarhus, Aarhus, Denmark.
    Severi, Gianluca
    Centre for Epidemiology and Population Health (U1018), Exposome and Heredity Team, Faculté de Médecine, Université Paris-Saclay, UVSQ, INSERM, Gustave Roussy, Villejuif, France; Department of Statistics, Computer Science, Applications “G. Parenti”, University of Florence, Florence, Italy.
    Kaaks, Rudolf
    German Cancer Research Center (DKFZ), Division of Cancer Epidemiology, Heidelberg, Germany.
    Katzke, Verena
    German Cancer Research Center (DKFZ), Division of Cancer Epidemiology, Heidelberg, Germany.
    Schulze, Matthias B.
    Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Arthur-Scheunert-Allee 114-116, Nuthetal, Germany; Institute of Nutritional Science, University of Potsdam, Nuthetal, Germany.
    Prada, Marcela
    Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Arthur-Scheunert-Allee 114-116, Nuthetal, Germany.
    Masala, Giovanna
    Institute for Cancer Research, Prevention and Clinical Network (ISPRO), Florence, Italy.
    Agnoli, Claudia
    Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian, 1, Milan, Italy.
    Panico, Salvatore
    Dipartimento Di Medicina Clinica E Chirurgia Federico Ii University, Naples, Italy.
    Sacerdote, Carlotta
    Unit of Cancer Epidemiology, Città della Salute e della Scienza University-Hospital and Center for Cancer Prevention (CPO), Via Santena 7, Turin, Italy.
    Jakszyn, Paula Gabriela
    Unit of Nutrition and Cancer, Cancer Epidemiology Research Programme, Catalan Institute of Oncology (ICO-IDIBELL), Barcelona, Spain; Blanquerna School of Health Sciences, Ramon Llull University, Barcelona, Spain.
    Sánchez, Maria-Jose
    Escuela Andaluza de Salud Pública (EASP), Granada, Spain; Instituto de Investigación Biosanitaria ibs.GRANADA, Granada, Spain; Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain; Department of Preventive Medicine and Public Health, University of Granada, Granada, Spain.
    Castilla, Jesús
    Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain; Instituto de Salud Pública de Navarra – IdiSNA, Pamplona, Spain.
    Chirlaque, María-Dolores
    Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain; Department of Epidemiology, Regional Health Council, IMIB-Arrixaca, Murcia University, Murcia, Spain.
    Atxega, Amaia Aizpurua
    Ministry of Health of the Basque Government, Sub Directorate for Public Health and Addictions of Gipuzkoa, San Sebastian, Spain; Biodonostia Health Research Institute, Epidemiology of Chronic and Communicable Diseases Group, San Sebastián, Spain.
    van Guelpen, Bethany
    Umeå universitet, Medicinska fakulteten, Wallenberg centrum för molekylär medicin vid Umeå universitet (WCMM). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Heath, Alicia K.
    Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom.
    Papier, Keren
    Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.
    Tong, Tammy Y.N.
    Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.
    Summers, Scott A.
    Department of Nutrition and Integrative Physiology and the Diabetes and Metabolism Research Center, University of Utah, UT, Salt Lake City, United States.
    Playdon, Mary
    Department of Nutrition and Integrative Physiology and the Diabetes and Metabolism Research Center, University of Utah, UT, Salt Lake City, United States; Cancer Control and Population Sciences, Huntsman Cancer Institute, UT, Salt Lake City, United States.
    Cross, Amanda J.
    Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom.
    Keski-Rahkonen, Pekka
    International Agency for Research on Cancer (IARC), 25 Av. Tony Garnier, Lyon, France.
    Chajès, Véronique
    International Agency for Research on Cancer (IARC), 25 Av. Tony Garnier, Lyon, France.
    Murphy, Neil
    International Agency for Research on Cancer (IARC), 25 Av. Tony Garnier, Lyon, France.
    Gunter, Marc J.
    International Agency for Research on Cancer (IARC), 25 Av. Tony Garnier, Lyon, France; Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom.
    Association between pre-diagnostic circulating lipid metabolites and colorectal cancer risk: a nested case–control study in the European Prospective Investigation into Cancer and Nutrition (EPIC)2024Ingår i: EBioMedicine, E-ISSN 2352-3964, Vol. 101, artikel-id 105024Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Altered lipid metabolism is a hallmark of cancer development. However, the role of specific lipid metabolites in colorectal cancer development is uncertain.

    Methods: In a case–control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC), we examined associations between pre-diagnostic circulating concentrations of 97 lipid metabolites (acylcarnitines, glycerophospholipids and sphingolipids) and colorectal cancer risk. Circulating lipids were measured using targeted mass spectrometry in 1591 incident colorectal cancer cases (55% women) and 1591 matched controls. Multivariable conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for associations between concentrations of individual lipid metabolites and metabolite patterns with colorectal cancer risk.

    Findings: Of the 97 assayed lipids, 24 were inversely associated (nominally p < 0.05) with colorectal cancer risk. Hydroxysphingomyelin (SM (OH)) C22:2 (ORper doubling 0.60, 95% CI 0.47–0.77) and acylakyl-phosphatidylcholine (PC ae) C34:3 (ORper doubling 0.71, 95% CI 0.59–0.87) remained associated after multiple comparisons correction. These associations were unaltered after excluding the first 5 years of follow-up after blood collection and were consistent according to sex, age at diagnosis, BMI, and colorectal subsite. Two lipid patterns, one including 26 phosphatidylcholines and all sphingolipids, and another 30 phosphatidylcholines, were weakly inversely associated with colorectal cancer.

    Interpretation: Elevated pre-diagnostic circulating levels of SM (OH) C22:2 and PC ae C34:3 and lipid patterns including phosphatidylcholines and sphingolipids were associated with lower colorectal cancer risk. This study may provide insight into potential links between specific lipids and colorectal cancer development. Additional prospective studies are needed to validate the observed associations. Funding: World Cancer Research Fund (reference: 2013/1002); European Commission (FP7: BBMRI-LPC; reference: 313010).

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  • 46.
    Harlid, Sophia
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Gunter, Marc J.
    Nutrition and Metabolism Branch, International Agency for Research on Cancer, Lyon, France.
    van Guelpen, Bethany
    Umeå universitet, Medicinska fakulteten, Wallenberg centrum för molekylär medicin vid Umeå universitet (WCMM). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Risk‐predictive and diagnostic biomarkers for colorectal cancer: a systematic review of studies using pre‐diagnostic blood samples collected in prospective cohorts and screening settings2021Ingår i: Cancers, ISSN 2072-6694, Vol. 13, nr 17, artikel-id 4406Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    This systematic review summarizes the evidence for blood‐based colorectal cancer biomarkers from studies conducted in pre‐diagnostic, asymptomatic settings. Of 1372 studies initially identified, the final selection included 30 studies from prospective cohorts and 23 studies from general screening settings. Overall, the investigations had high quality but considerable variability in data analysis and presentation of results, and few biomarkers demonstrated a clinically relevant discriminatory ability. One of the most promising biomarkers was the anti‐p53 antibody, with consistent findings in one screening cohort and in the 3–4 years prior to diagnosis in two prospective cohort studies. Proteins were the most common type of biomarker assessed, particularly carcinoembryonic antigen (CEA) and C‐reactive protein (CRP), with modest results. Other potentially promising biomarkers included proteins, such as AREG, MIC‐1/GDF15, LRG1 and FGF‐21, metabolites and/or metabolite profiles, non‐coding RNAs and DNA methylation, as well as re‐purposed routine lab tests, such as ferritin and the triglyceride–glucose index. Biomarker panels generally achieved higher discriminatory performance than single markers. In conclusion, this systematic review highlighted anti‐p53 antibodies as a promising blood‐based biomarker for use in colorectal cancer screening panels, together with other specific proteins. It also underscores the need for validation of promising biomarkers in independent pre‐diagnostic settings.

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  • 47.
    Harlid, Sophia
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Harbs, Justin
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Myte, Robin
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Brunius, Carl
    Department of Biology and Biological Engineering, Chalmers University of Technology, Gothenburg, Sweden; Chalmers Mass Spectrometry Infrastructure, Chalmers University of Technology, Gothenburg, Sweden.
    Gunter, Marc J.
    Section of Nutrition and Metabolism, International Agency for Research On Cancer, World Health Organization, Lyon, France.
    Palmqvist, Richard
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Liu, Xijia
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för matematik och matematisk statistik.
    van Guelpen, Bethany
    Umeå universitet, Medicinska fakulteten, Wallenberg centrum för molekylär medicin vid Umeå universitet (WCMM). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    A two-tiered targeted proteomics approach to identify pre-diagnostic biomarkers of colorectal cancer risk2021Ingår i: Scientific Reports, E-ISSN 2045-2322, Vol. 11, nr 1, artikel-id 5151Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Colorectal cancer prognosis is dependent on stage, and measures to improve early detection are urgently needed. Using prospectively collected plasma samples from the population-based Northern Sweden Health and Disease Study, we evaluated protein biomarkers in relation to colorectal cancer risk. Applying a two-tiered approach, we analyzed 160 proteins in matched sequential samples from 58 incident colorectal cancer case–control pairs. Twenty-one proteins selected from both this discovery phase and the literature were then analyzed in a validation set of 450 case–control pairs. Odds ratios were estimated by conditional logistic regression. LASSO regression and ROC analysis were used for multi-marker analyses. In the main validation analysis, no proteins retained statistical significance. However, exploratory subgroup analyses showed associations between FGF-21 and colon cancer risk (multivariable OR per 1 SD: 1.23 95% CI 1.03–1.47) as well as between PPY and rectal cancer risk (multivariable OR per 1 SD: 1.47 95% CI 1.12–1.92). Adding protein markers to basic risk predictive models increased performance modestly. Our results highlight the challenge of developing biomarkers that are effective in the asymptomatic, prediagnostic window of opportunity for early detection of colorectal cancer. Distinguishing between cancer subtypes may improve prediction accuracy. However, single biomarkers or small panels may not be sufficient for effective precision screening.

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  • 48.
    Harlid, Sophia
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Myte, Robin
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Van Guelpen, Bethany
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Replication of Epigenome-wide Associations Related to Body Mass Index Using the Infinium MethylationEPIC BeadChip on Repeated Samples2017Ingår i: Genetic Epidemiology, ISSN 0741-0395, E-ISSN 1098-2272, Vol. 41, nr 7, s. 680-680Artikel i tidskrift (Övrigt vetenskapligt)
  • 49.
    Harlid, Sophia
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Myte, Robin
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    van Guelpen, Bethany
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    The metabolic syndrome, inflammation and colorectal cancer risk: an evaluation of large panels of plasma protein markers using repeated, prediagnostic samples2017Ingår i: Mediators of Inflammation, ISSN 0962-9351, E-ISSN 1466-1861, artikel-id 4803156Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Metabolic syndrome (MetS), a set of metabolic risk factors including obesity, dysglycemia, and dyslipidemia, is associated with increased colorectal cancer (CRC) risk. A putative biological mechanism is chronic, low-grade inflammation, both a feature of MetS and a CRC risk factor. However, excess body fat also induces a proinflammatory state and increases CRC risk. In order to explore the relationship between MetS, body size, inflammation, and CRC, we studied large panels of inflammatory and cancer biomarkers. We included 138 participants from the Västerbotten Intervention Programme with repeated sampling occasions, 10 years apart. Plasma samples were analyzed for 178 protein markers by proximity extension assay. To identify associations between plasma protein levels and MetS components, linear mixed models were fitted for each protein. Twelve proteins were associated with at least one MetS component, six of which were associated with MetS score. MetS alone was not related to any protein. Instead, BMI displayed by far the strongest associations with the biomarkers. One of the 12 MetS score-related proteins (FGF-21), also associated with BMI, was associated with an increased CRC risk (OR 1.71, 95% CI 1.19–2.47). We conclude that overweight and obesity, acting through both inflammation and other mechanisms, likely explain the MetS-CRC connection.

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  • 50.
    Harlid, Sophia
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    van Guelpen, Bethany
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi. Umeå universitet, Medicinska fakulteten, Wallenberg centrum för molekylär medicin vid Umeå universitet (WCMM).
    Qu, Conghui
    Gylling, Björn
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Aglago, Elom K.
    Amitay, Efrat L.
    Brenner, Hermann
    Buchanan, Daniel D.
    Campbell, Peter T.
    Cao, Yin
    Chan, Andrew T.
    Chang-Claude, Jenny
    Drew, David A.
    Figueiredo, Jane C.
    French, Amy J.
    Gallinger, Steven
    Giannakis, Marios
    Giles, Graham G.
    Gunter, Marc J.
    Hoffmeister, Michael
    Hsu, Li
    Jenkins, Mark A.
    Lin, Yi
    Moreno, Victor
    Murphy, Neil
    Newcomb, Polly A.
    Newton, Christina C.
    Nowak, Jonathan A.
    Obón-Santacana, Mireia
    Ogino, Shuji
    Potter, John D.
    Song, Mingyang
    Steinfelder, Robert S.
    Sun, Wei
    Thibodeau, Stephen N.
    Toland, Amanda E.
    Ugai, Tomotaka
    Um, Caroline Y.
    Woods, Michael O.
    Phipps, Amanda I.
    Harrison, Tabitha
    Peters, Ulrike
    Diabetes mellitus in relation to colorectal tumor molecular subtypes: a pooled analysis of more than 9000 cases2022Ingår i: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 151, nr 3, s. 348-360Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Diabetes is an established risk factor for colorectal cancer. However, colorectal cancer is a heterogeneous disease and it is not well understood whether diabetes is more strongly associated with some tumor molecular subtypes than others. A better understanding of the association between diabetes and colorectal cancer according to molecular subtypes could provide important insights into the biology of this association. We used data on lifestyle and clinical characteristics from the Colorectal Cancer Family Registry (CCFR) and the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO), including 9756 colorectal cancer cases (with tumor marker data) and 9985 controls, to evaluate associations between reported diabetes and risk of colorectal cancer according to molecular subtypes. Tumor markers included BRAF and KRAS mutations, microsatellite instability and CpG island methylator phenotype. In the multinomial logistic regression model, comparing colorectal cancer cases to cancer-free controls, diabetes was positively associated with colorectal cancer regardless of subtype. The highest OR estimate was found for BRAF-mutated colorectal cancer, n = 1086 (ORfully adj: 1.67, 95% confidence intervals [CI]: 1.36-2.05), with an attenuated association observed between diabetes and colorectal cancer without BRAF-mutations, n = 7959 (ORfully adj: 1.33, 95% CI: 1.19-1.48). In the case only analysis, BRAF-mutation was differentially associated with diabetes (Pdifference = .03). For the other markers, associations with diabetes were similar across tumor subtypes. In conclusion, our study confirms the established association between diabetes and colorectal cancer risk, and suggests that it particularly increases the risk of BRAF-mutated tumors.

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