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  • 1.
    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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  • 2. Aglago, Elom K.
    et al.
    Rinaldi, Sabina
    Freisling, Heinz
    Jiao, Li
    Hughes, David J.
    Fedirko, Veronika
    Schalkwijk, Casper G.
    Weiderpass, Elisabete
    Dahm, Christina C.
    Overvad, Kim
    Eriksen, Anne Kirstine
    Kyrø, Cecilie
    Boutron-Ruault, Marie-Christine
    Rothwell, Joseph A.
    Severi, Gianluca
    Katzke, Verena
    Kühn, Tilman
    Schulze, Matthias B.
    Aleksandrova, Krasimira
    Masala, Giovanna
    Krogh, Vittorio
    Panico, Salvatore
    Tumino, Rosario
    Naccarati, Alessio
    Bueno-de-Mesquita, Bas
    van Gils, Carla H.
    Sandanger, Torkjel M.
    Gram, Inger T.
    Skeie, Guri
    Quirós, J. Ramón
    Jakszyn, Paula
    Sánchez, Maria-Jose
    Amiano, Pilar
    Huerta, José María
    Ardanaz, Eva
    Johansson, Ingegerd
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi. Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    Harlid, Sophia
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Perez-Cornago, Aurora
    Mayén, Ana-Lucia
    Cordova, Reynalda
    Gunter, Marc J.
    Vineis, Paolo
    Cross, Amanda J.
    Riboli, Elio
    Jenab, Mazda
    Soluble Receptor for Advanced Glycation End-products (sRAGE) and Colorectal Cancer Risk: A Case-Control Study Nested within a European Prospective Cohort2021Ingår i: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 30, nr 1, s. 182-192Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Overexpression of the receptor for advanced glycation end-product (RAGE) has been associated with chronic inflammation, which in turn has been associated with increased colorectal cancer risk. Soluble RAGE (sRAGE) competes with RAGE to bind its ligands, thus potentially preventing RAGE-induced inflammation.

    METHODS: To investigate whether sRAGE and related genetic variants are associated with colorectal cancer risk, we conducted a nested case-control study in the European Prospective Investigation into Cancer and Nutrition (EPIC). Plasma sRAGE concentrations were measured by ELISA in 1,361 colorectal cancer matched case-control sets. Twenty-four SNPs encoded in the genes associated with sRAGE concentrations were available for 1,985 colorectal cancer cases and 2,220 controls. Multivariable adjusted ORs and 95% confidence intervals (CIs) were computed using conditional and unconditional logistic regression for colorectal cancer risk and circulating sRAGE and SNPs, respectively.

    RESULTS: Higher sRAGE concentrations were inversely associated with colorectal cancer (ORQ5vs.Q1, 0.77; 95% CI, 0.59-1.00). Sex-specific analyses revealed that the observed inverse risk association was restricted to men (ORQ5vs.Q1, 0.63; 95% CI, 0.42-0.94), whereas no association was observed in women (ORQ5vs.Q1, 1.00; 95% CI, 0.68-1.48; Pheterogeneity for sex = 0.006). Participants carrying minor allele of rs653765 (promoter region of ADAM10) had lower colorectal cancer risk (C vs. T, OR, 0.90; 95% CI, 0.82-0.99).

    CONCLUSIONS: Prediagnostic sRAGE concentrations were inversely associated with colorectal cancer risk in men, but not in women. An SNP located within ADAM10 gene, pertaining to RAGE shedding, was associated with colorectal cancer risk.

    IMPACT: Further studies are needed to confirm our observed sex difference in the association and better explore the potential involvement of genetic variants of sRAGE in colorectal cancer development.

  • 3. 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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  • 4.
    Allione, Alessandra
    et al.
    Department of Medical Sciences, University of Turin, Turin, Italy.
    Viberti, Clara
    Department of Medical Sciences, University of Turin, Turin, Italy.
    Cotellessa, Ilaria
    Department of Medical Sciences, University of Turin, Turin, Italy.
    Catalano, Chiara
    Department of Medical Sciences, University of Turin, Turin, Italy.
    Casalone, Elisabetta
    Department of Medical Sciences, University of Turin, Turin, Italy.
    Cugliari, Giovanni
    Department of Medical Sciences, University of Turin, Turin, Italy.
    Russo, Alessia
    Department of Medical Sciences, University of Turin, Turin, Italy.
    Guarrera, Simonetta
    Candiolo Cancer Institute, FPO—IRCCS, Candiolo, Italy.
    Mirabelli, Dario
    Cancer Epidemiology Unit, Department of Medical Sciences, University of Turin, Turin, Italy; Interdepartmental Center for Studies on Asbestos and Other Toxic Particulates “G. Scansetti”, University of Turin, Turin, Italy.
    Sacerdote, Carlotta
    Unit of Cancer Epidemiology, Città Della Salute e Della Scienza University-Hospital and Center for Cancer Prevention (CPO), Turin, Italy.
    Gentile, Marco
    A.O.U. Federico II, Naples, Italy.
    Eichelmann, Fabian
    Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany; German Center for Diabetes Research (DZD), Neuherberg, Germany.
    Schulze, Matthias B.
    Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany; University of Potsdam, Institute of Nutritional Science, Nuthetal, Germany.
    Harlid, Sophia
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Eriksen, Anne Kirstine
    Danish Cancer Society Research Center, Diet, Genes and Environment, Copenhagen, Denmark.
    Tjønneland, Anne
    Danish Cancer Society Research Center, Diet, Genes and Environment, Copenhagen, Denmark; Department of Public Health, University of Copenhagen, Copenhagen, Denmark.
    Andersson, Martin
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för hållbar hälsa.
    Dollé, Martijn E.T.
    Centre for Health Protection National Institute for Public Health and the Environment, Bilthoven, Netherlands.
    Van Puyvelde, Heleen
    International Agency for Research on Cancer, World Health Organisation, Lyon, France.
    Weiderpass, Elisabete
    International Agency for Research on Cancer, World Health Organisation, Lyon, France.
    Rodriguez-Barranco, Miguel
    Escuela Andaluza de Salud Pública (EASP), Granada, Spain; Instituto de Investigación Biosanitaria ibs.GRANADA, Granada, Spain; CIBER in Epidemiology and Public Health (CIBERESP), Madrid, Spain.
    Agudo, Antonio
    Unit of Nutrition and Cancer, Catalan Institute of Oncology—ICO, L'Hospitalet de Llobregat, Barcelona, Spain; Nutrition and Cancer Group, Epidemiology, Public Health, Cancer Prevention and Palliative Care Program, Bellvitge Biomedical Research Institute—IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain.
    Heath, Alicia K.
    Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom.
    Chirlaque, María-Dolores
    CIBER in Epidemiology and Public Health (CIBERESP), Madrid, Spain; Department of Epidemiology, Regional Health Council, IMIB-Arrixaca, Murcia University, Murcia, Spain.
    Truong, Thérèse
    Université Paris-Saclay, UVSQ, Inserm, CESP U1018, “Exposome, Heredity, Cancer and Health” Team, Paris, France.
    Dragic, Dzevka
    Université Paris-Saclay, UVSQ, Inserm, CESP U1018, “Exposome, Heredity, Cancer and Health” Team, Paris, France; Centre de Recherche sur le Cancer de l'Université Laval, Département de Médecine Sociale et Préventive, Faculté de Médecine, Québec, Canada; Axe Oncologie, Centre de Recherche du CHU de Québec-Université Laval, Québec, Canada.
    Severi, Gianluca
    Université Paris-Saclay, UVSQ, Inserm, CESP U1018, “Exposome, Heredity, Cancer and Health” Team, Paris, France; Department of Statistics, Computer Science and Applications “G. Parenti” (DISIA), University of Florence, Florence, Italy.
    Sieri, Sabina
    Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano Via Venezian, Milan, Italy.
    Sandanger, Torkjel M.
    Department of Community Medicine, UiT The Arctic University of Norway, Tromsø, Norway.
    Ardanaz, Eva
    CIBER in Epidemiology and Public Health (CIBERESP), Madrid, Spain; Navarra Public Health Institute, Pamplona, Spain; IdiSNA, Navarra Institute for Health Research, Pamplona, Spain.
    Vineis, Paolo
    MRC Centre for Environment and Health, Imperial College London, London, United Kingdom.
    Matullo, Giuseppe
    Department of Medical Sciences, University of Turin, Turin, Italy; Interdepartmental Center for Studies on Asbestos and Other Toxic Particulates “G. Scansetti”, University of Turin, Turin, Italy; Medical Genetics Unit, AOU Città della Salute e Della Scienza, Turin, Italy.
    Blood cell DNA methylation biomarkers in preclinical malignant pleural mesothelioma: the EPIC prospective cohort2022Ingår i: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 152, nr 4, s. 725-737Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Malignant pleural mesothelioma (MPM) is a rare and aggressive cancer mainly caused by asbestos exposure. Specific and sensitive noninvasive biomarkers may facilitate and enhance screening programs for the early detection of cancer. We investigated DNA methylation (DNAm) profiles in MPM prediagnostic blood samples in a case-control study nested in the European Prospective Investigation into Cancer and nutrition (EPIC) cohort, aiming to characterise DNAm biomarkers associated with MPM. From the EPIC cohort, we included samples from 135 participants who developed MPM during 20 years of follow-up and from 135 matched, cancer-free, controls. For the discovery phase we selected EPIC participants who developed MPM within 5 years from enrolment (n = 36) with matched controls. We identified nine differentially methylated CpGs, selected by 10-fold cross-validation and correlation analyses: cg25755428 (MRI1), cg20389709 (KLF11), cg23870316, cg13862711 (LHX6), cg06417478 (HOOK2), cg00667948, cg01879420 (AMD1), cg25317025 (RPL17) and cg06205333 (RAP1A). Receiver operating characteristic (ROC) analysis showed that the model including baseline characteristics (age, sex and PC1wbc) along with the nine MPM-related CpGs has a better predictive value for MPM occurrence than the baseline model alone, maintaining some performance also at more than 5 years before diagnosis (area under the curve [AUC] < 5 years = 0.89; AUC 5-10 years = 0.80; AUC >10 years = 0.75; baseline AUC range = 0.63-0.67). DNAm changes as noninvasive biomarkers in prediagnostic blood samples of MPM cases were investigated for the first time. Their application can improve the identification of asbestos-exposed individuals at higher MPM risk to possibly adopt more intensive monitoring for early disease identification.

  • 5. 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.

  • 6. Bjørge, Tone
    et al.
    Häggström, Christel
    Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning. Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning. Department of Surgical Sciences, Uppsala University, Uppsala, Sweden..
    Ghaderi, Sara
    Nagel, Gabriele
    Manjer, Jonas
    Tretli, Steinar
    Ulmer, Hanno
    Harlid, Sophia
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Rosendahl, Ann H.
    Lang, Alois
    Stattin, Pär
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Stocks, Tanja
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Engeland, Anders
    BMI and weight changes and risk of obesity-related cancers: a pooled European cohort study2019Ingår i: International Journal of Epidemiology, ISSN 0300-5771, E-ISSN 1464-3685, Vol. 48, nr 6, s. 1872-2885Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Obesity is an established risk factor for several cancers. Adult weight gain has been associated with increased cancer risk, but studies on timing and duration of adult weight gain are relatively scarce. We examined the impact of BMI (body mass index) and weight changes over time, as well as the timing and duration of excess weight, on obesity- and non-obesity-related cancers.

    Methods: We pooled health data from six European cohorts and included 221 274 individuals with two or more height and weight measurements during 1972–2014. Several BMI and weight measures were constructed. Cancer cases were identified through linkage with national cancer registries. Hazard ratios (HRs) of cancer with 95% confidence intervals (CIs) were derived from time-dependent Cox-regression models.

    Results: During follow-up, 27 881 cancer cases were diagnosed; 9761 were obesity-related. The HR of all obesity-related cancers increased with increasing BMI at first and last measurement, maximum BMI and longer duration of overweight (men only) and obesity. Participants who were overweight before age 40 years had an HR of obesity-related cancers of 1.16 (95% CI 1.02, 1.32) and 1.15 (95% CI 1.04, 1.27) in men and women, respectively, compared with those who were not overweight. The risk increase was particularly high for endometrial (70%), male renal-cell (58%) and male colon cancer (29%). No positive associations were seen for cancers not regarded as obesity-related.

    Conclusions: Adult weight gain was associated with increased risk of several major cancers. The degree, timing and duration of overweight and obesity also seemed to be important. Preventing weight gain may reduce the cancer risk.

  • 7.
    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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  • 8.
    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.

  • 9.
    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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  • 10.
    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)
  • 11.
    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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  • 12.
    Borozan, Ivan
    et al.
    Ontario Institute for Cancer Research, ON, Toronto, Canada.
    Zaidi, Syed H.
    Ontario Institute for Cancer Research, ON, Toronto, Canada.
    Harrison, Tabitha A.
    Public Health Sciences Division, Fred Hutchinson Cancer Research Centre, WA, Seattle, United States.
    Phipps, Amanda I.
    Public Health Sciences Division, Fred Hutchinson Cancer Research Centre, WA, Seattle, United States.
    Zheng, Jiayin
    Public Health Sciences Division, Fred Hutchinson Cancer Research Centre, WA, Seattle, United States.
    Lee, Stephen
    Ontario Institute for Cancer Research, ON, Toronto, Canada.
    Trinh, Quang M.
    Ontario Institute for Cancer Research, ON, Toronto, Canada.
    Steinfelder, Robert S.
    Public Health Sciences Division, Fred Hutchinson Cancer Research Centre, WA, Seattle, United States.
    Adams, Jeremy
    Ontario Institute for Cancer Research, ON, Toronto, Canada.
    Banbury, Barbara L.
    Public Health Sciences Division, Fred Hutchinson Cancer Research Centre, WA, Seattle, United States.
    Berndt, Sonja I.
    Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, MD, Bethesda, United States.
    Brezina, Stefanie
    Institute of Cancer Research, Department of Medicine I, Medical University of Vienna, Vienna, Austria.
    Buchanan, Daniel D.
    Colorectal Oncogenomics Group, Department of Clinical Pathology, The University of Melbourne, VIC, Parkville, Australia; The University of Melbourne Centre for Cancer Research, Victorian Comprehensive Cancer Centre, VIC, Parkville, Australia; Familial Cancer Clinic, Genetic Medicine, The Royal Melbourne Hospital, VIC, Parkville, Australia; Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, VIC, Parkville, Australia.
    Bullman, Susan
    Human Biology Division, Fred Hutchinson Cancer Research Center, WA, Seattle, United States.
    Cao, Yin
    Division of Public Health Sciences, Department of Surgery, Washington University School of Medicine in St. Louis, St Louis, MO, United States; Siteman Cancer Center, Washington University School of Medicine in St. Louis, St Louis, MO, United States.
    Farris III, Alton B.
    Pathology and Laboratory Medicine, Emory University, School of Medicine, GA, Atlanta, United States.
    Figueiredo, Jane C.
    Department of Medicine, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, CA, Los Angeles, United States.
    Giannakis, Marios
    Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, MA, Boston, United States; Broad Institute of MIT and Harvard, MA, Cambridge, United States.
    Heisler, Lawrence E.
    Ontario Institute for Cancer Research, ON, Toronto, Canada.
    Hopper, John L.
    The University of Melbourne Centre for Cancer Research, Victorian Comprehensive Cancer Centre, VIC, Parkville, Australia.
    Lin, Yi
    Public Health Sciences Division, Fred Hutchinson Cancer Research Centre, WA, Seattle, United States.
    Luo, Xuemei
    Ontario Institute for Cancer Research, ON, Toronto, Canada.
    Nishihara, Reiko
    Department of Oncologic Pathology, Dana-Farber Cancer Institute and Harvard Medical School, MA, Boston, United States; Department of Nutrition, Harvard T.H. Chan School of Public Health, MA, Boston, United States; Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, MA, Boston, United States.
    Mardis, Elaine R.
    The Steve and Cindy Rasmussen Institute for Genomic Medicine, Abigail Wexner Research Institute, Nationwide Children's Hospital, OH, Columbus, United States.
    Papadopoulos, Nickolas
    Ludwig Center for Cancer Genetics and Therapeutics, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Medicine, MD, Baltimore, United States.
    Qu, Conghui
    Public Health Sciences Division, Fred Hutchinson Cancer Research Centre, WA, Seattle, United States.
    Reid, Emma E.G.
    Ontario Institute for Cancer Research, ON, Toronto, Canada.
    Thibodeau, Stephen N.
    Division of Laboratory Genetics, Department of Laboratory Medicine and Pathology, Mayo Clinic, MN, Rochester, United States.
    Harlid, Sophia
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Um, Caroline Y.
    Behavioral and Epidemiology Research Group, American Cancer Society, GA, Atlanta, United States.
    Hsu, Li
    Public Health Sciences Division, Fred Hutchinson Cancer Research Centre, WA, Seattle, United States; Department of Biostatistics, School of Public Health, University of Washington, WA, Seattle, United States.
    Gsur, Andrea
    Institute of Cancer Research, Department of Medicine I, Medical University of Vienna, Vienna, Austria.
    Campbell, Peter T.
    Behavioral and Epidemiology Research Group, American Cancer Society, GA, Atlanta, United States.
    Gallinger, Steven
    Ontario Institute for Cancer Research, ON, Toronto, Canada; Lunenfeld-Tanenbaum Research Institute, Sinai Health, University of Toronto, ON, Toronto, Canada; General Surgery, Surgery and Critical Care Program, University Health Network Toronto General Hospital, University of Toronto, ON, Toronto, Canada.
    Newcomb, Polly A.
    Public Health Sciences Division, Fred Hutchinson Cancer Research Centre, WA, Seattle, United States; Department of Epidemiology, School of Public Health, University of Washington, WA, Seattle, United States.
    Ogino, Shuji
    Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, MA, Boston, United States; Department of Nutrition, Harvard T.H. Chan School of Public Health, MA, Boston, United States; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Harvard University, MA, Boston, United States; Cancer Immunology Program, Dana-Farber/Harvard Cancer Center, MA, Boston, United States; Cancer Epidemiology Program, Dana-Farber/Harvard Cancer Center, MA, Boston, United States.
    Sun, Wei
    Public Health Sciences Division, Fred Hutchinson Cancer Research Centre, WA, Seattle, United States.
    Hudson, Thomas J.
    Ontario Institute for Cancer Research, ON, Toronto, Canada.
    Ferretti, Vincent
    Ontario Institute for Cancer Research, ON, Toronto, Canada; CHU Sainte-Justine Research Center, University of Montreal, QC, Montreal, Canada.
    Peters, Ulrike
    Public Health Sciences Division, Fred Hutchinson Cancer Research Centre, WA, Seattle, United States; Department of Epidemiology, School of Public Health, University of Washington, WA, Seattle, United States.
    Molecular and Pathology Features of Colorectal Tumors and Patient Outcomes Are Associated with Fusobacterium nucleatum and Its Subspecies animalis2022Ingår i: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 31, nr 1, s. 210-220Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Fusobacterium nucleatum (F. nucleatum) activates oncogenic signaling pathways and induces inflammation to promote colorectal carcinogenesis.

    Methods: We characterized F. nucleatum and its subspecies in colorectal tumors and examined associations with tumor characteristics and colorectal cancer-specific survival. We conducted deep sequencing of nusA, nusG, and bacterial 16s rRNA genes in tumors from 1,994 patients with colorectal cancer and assessed associations between F. nucleatum presence and clinical characteristics, colorectal cancer-specific mortality, and somatic mutations.

    Results: F. nucleatum, which was present in 10.3% of tumors, was detected in a higher proportion of right-sided and advanced-stage tumors, particularly subspecies animalis. Presence of F. nucleatum was associated with higher colorectal cancer-specific mortality (HR, 1.97; P = 0.0004). This association was restricted to nonhypermutated, microsatellite-stable tumors (HR, 2.13; P = 0.0002) and those who received chemotherapy [HR, 1.92; confidence interval (CI), 1.07-3.45; P = 0.029). Only F. nucleatum subspecies animalis, the main subspecies detected (65.8%), was associated with colorectal cancer-specific mortality (HR, 2.16; P = 0.0016), subspecies vincentii and nucleatum were not (HR, 1.07; P = 0.86). Additional adjustment for tumor stage suggests that the effect of F. nucleatum on mortality is partly driven by a stage shift. Presence of F. nucleatum was associated with microsatellite instable tumors, tumors with POLE exonuclease domain mutations, and ERBB3 mutations, and suggestively associated with TP53 mutations.

    Conclusions: F. nucleatum, and particularly subspecies animalis, was associated with a higher colorectal cancer-specific mortality and specific somatic mutated genes.

  • 13.
    Botteri, Edoardo
    et al.
    Section for Colorectal Cancer Screening, Cancer Registry of Norway, Oslo, Norway; Department of Research, Cancer Registry of Norway, Oslo, Norway.
    Peveri, Giulia
    Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milan, Italy; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Berstad, Paula
    Section for Colorectal Cancer Screening, Cancer Registry of Norway, Oslo, Norway.
    Bagnardi, Vincenzo
    Department of Statistics and Quantitative Methods, University of Milan-Bicocca, Milan, Italy.
    Chen, Sairah L.F.
    Department of Community Medicine, UiT The Arctic University of Norway, Tromsø, Norway.
    Sandanger, Torkjel M.
    Department of Community Medicine, UiT The Arctic University of Norway, Tromsø, Norway.
    Hoff, Geir
    Section for Colorectal Cancer Screening, Cancer Registry of Norway, Oslo, Norway; Department of Research, Telemark Hospital, Skien, Norway.
    Dahm, Christina C.
    Department of Public Health, Aarhus University, Denmark.
    Antoniussen, Christian S.
    Department of Public Health, Aarhus University, Denmark.
    Tjønneland, Anne
    Danish Cancer Society Research Center, Copenhagen, Denmark.
    Eriksen, Anne Kirstine
    Danish Cancer Society Research Center, Copenhagen, Denmark.
    Skeie, Guri
    Department of Community Medicine, UiT The Arctic University of Norway, Tromsø, Norway.
    Perez-Cornago, Aurora
    Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.
    Huerta, José María
    Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca, Murcia, Spain; CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain.
    Jakszyn, Paula
    Unit of Nutrition and Cancer, Cancer Epidemiology Research Programme, Catalan Institute of Oncology (ICO-IDIBELL), Barcelona, Spain.
    Harlid, Sophia
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Sundström, Björn
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Barricarte, Aurelio
    CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain; Navarra Public Health Institute, Pamplona, Spain; Navarra Institute for Health Research (IdiSNA), Pamplona, Spain.
    Monninkhof, Evelyn M.
    Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands.
    Derksen, Jeroen W.G.
    Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands.
    Schulze, Matthias B.
    Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany; Institute of Nutritional Science, University of Potsdam, Nuthetal, Germany.
    Bueno-De-Mesquita, Bas
    Centre for Nutrition, Prevention and Health Services, National Institute for Public Health and the Environment (RIVM), Bilthoven, Netherlands.
    Sánchez, Maria-Jose
    CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain; 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.
    Cross, Amanda J.
    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; Department of Hygiene and Epidemiology, University of Ioannina, School of Medicine, Ioannina, Greece.
    De Magistris, Maria Santucci
    Azienda Ospedaliera Universitaria Federico II di Napoli, Napoli, Italy.
    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.
    Rothwell, Joseph A.
    Université Paris-Saclay, UVSQ, Inserm, CESP U1018, 'Exposome, Heredity, Cancer and Health' Team, Gustave Roussy, Villejuif, France.
    Laouali, Nasser
    Université Paris-Saclay, UVSQ, Inserm, CESP U1018, 'Exposome, Heredity, Cancer and Health' Team, Gustave Roussy, Villejuif, France.
    Severi, Gianluca
    Université Paris-Saclay, UVSQ, Inserm, CESP U1018, 'Exposome, Heredity, Cancer and Health' Team, Gustave Roussy, Villejuif, France; Department of Statistics, Computer Science, Applications 'G. Parenti' (DISIA), University of Florence, Florence, Italy.
    Amiano, Pilar
    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; Spanish Consortium for Research on Epidemiology and Public Health (CIBERESP), Instituto de Salud Carlos III, Madrid, Spain.
    Contiero, Paolo
    Environmental Epidemiology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
    Sacerdote, Carlotta
    Unit of Cancer Epidemiology, Città della Salute e della Scienza University-Hospital, Turin, Italy.
    Goldberg, Marcel
    Population-based Epidemiologic Cohorts Unit, Inserrm UMS 11, Villejuif, France.
    Touvier, Mathilde
    Nutritional Epidemiology Research Team (EREN), Sorbonne Paris Nord University, Inserm U1153, Inrae U1125, Cnam, Epidemiology and Statistics Research Center - University of Paris (CRESS), Bobigny, France; Public Health Department, Avicenne Hospital, AP-HP, Bobigny, France.
    Freisling, Heinz
    International Agency for Research on Cancer, World Health Organization, Lyon, France.
    Viallon, Vivian
    International Agency for Research on Cancer, World Health Organization, Lyon, France.
    Weiderpass, Elisabete
    International Agency for Research on Cancer, World Health Organization, Lyon, France.
    Riboli, Elio
    Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom.
    Gunter, Marc J.
    International Agency for Research on Cancer, World Health Organization, Lyon, France.
    Jenab, Mazda
    International Agency for Research on Cancer, World Health Organization, Lyon, France.
    Ferrari, Pietro
    International Agency for Research on Cancer, World Health Organization, Lyon, France.
    Changes in lifestyle and risk of colorectal cancer in the european prospective investigation into cancer and nutrition2023Ingår i: American Journal of Gastroenterology, ISSN 0002-9270, E-ISSN 1572-0241, Vol. 118, nr 4, s. 702-711Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Introduction: We investigated the impact of changes in lifestyle habits on colorectal cancer (CRC) risk in a multicountry European cohort.

    Methods: We used baseline and follow-up questionnaire data from the European Prospective Investigation into Cancer cohort to assess changes in lifestyle habits and their associations with CRC development. We calculated a healthy lifestyle index (HLI) score based on smoking status, alcohol consumption, body mass index, and physical activity collected at the 2 time points. HLI ranged from 0 (most unfavorable) to 16 (most favorable). We estimated the association between HLI changes and CRC risk using Cox regression models and reported hazard ratios (HR) with 95% confidence intervals (CI).

    Results: Among 295,865 participants, 2,799 CRC cases were observed over a median of 7.8 years. The median time between questionnaires was 5.7 years. Each unit increase in HLI from the baseline to the follow-up assessment was associated with a statistically significant 3% lower CRC risk. Among participants in the top tertile at baseline (HLI > 11), those in the bottom tertile at follow-up (HLI ≤ 9) had a higher CRC risk (HR 1.34; 95% CI 1.02-1.75) than those remaining in the top tertile. Among individuals in the bottom tertile at baseline, those in the top tertile at follow-up had a lower risk (HR 0.77; 95% CI 0.59-1.00) than those remaining in the bottom tertile.

    Discussion: Improving adherence to a healthy lifestyle was inversely associated with CRC risk, while worsening adherence was positively associated with CRC risk. These results justify and support recommendations for healthy lifestyle changes and healthy lifestyle maintenance for CRC prevention.

  • 14. 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.

  • 15. 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.

  • 16. Butt, Salma
    et al.
    Harlid, Sophia
    Lund University, Department of Laboratory Sciences.
    Borgquist, Signe
    Ivarsson, Malin
    Landberg, Göran
    Dillner, Joakim
    Carlson, Joyce
    Manjer, Jonas
    Genetic predisposition, parity, age at first childbirth and risk for breast cancer.2012Ingår i: BMC Research Notes, E-ISSN 1756-0500, Vol. 5, artikel-id 414Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Recent studies have identified several single-nucleotide polymorphisms (SNPs) associated with the risk of breast cancer and parity and age at first childbirth are well established and important risk factors for breast cancer. The aim of the present study was to examine the interaction between these environmental factors and genetic variants on breast cancer risk.

    METHODS: The Malmö Diet and Cancer Study (MDCS) included 17 035 female participants, from which 728 incident breast cancer cases were matched to 1448 controls. The associations between 14 SNPs and breast cancer risk were investigated in different strata of parity and age at first childbirth. A logistic regression analysis for the per allele risk, adjusted for potential confounders yielded odds ratios (OR) with 95% confidence intervals (CI).

    RESULTS: Six of the previously identified SNPs showed a statistically significant association with breast cancer risk: rs2981582 (FGFR2), rs3803662 (TNRC9), rs12443621 (TNRC9), rs889312 (MAP3K1), rs3817198 (LSP1) and rs2107425 (H19). We could not find any statistically significant interaction between the effects of tested SNPs and parity/age at first childbirth on breast cancer risk after adjusting for multiple comparisons.

    CONCLUSIONS: The results of this study are in agreement with previous studies of null interactions between tested SNPs and parity/age at first childbirth with regard to breast cancer risk.

  • 17. Christakoudi, Sofia
    et al.
    Kakourou, Artemisia
    Markozannes, Georgios
    Tzoulaki, Ioanna
    Weiderpass, Elisabete
    Brennan, Paul
    Gunter, Marc
    Dahm, Christina C.
    Overvad, Kim
    Olsen, Anja
    Tjønneland, Anne
    Boutron-Ruault, Marie-Christine
    Madika, Anne-Laure
    Severi, Gianluca
    Katzke, Verena
    Kühn, Tilman
    Bergmann, Manuela M.
    Boeing, Heiner
    Karakatsani, Anna
    Martimianaki, Georgia
    Thriskos, Paschalis
    Masala, Giovanna
    Sieri, Sabina
    Panico, Salvatore
    Tumino, Rosario
    Ricceri, Fulvio
    Agudo, Antonio
    Redondo-Sánchez, Daniel
    Colorado-Yohar, Sandra M.
    Mokoroa, Olatz
    Melander, Olle
    Stocks, Tanja
    Häggström, Christel
    Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning. Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
    Harlid, Sophia
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Bueno-de-Mesquita, Bas
    van Gils, Carla H.
    Vermeulen, Roel C. H.
    Khaw, Kay-Tee
    Wareham, Nicholas J.
    Tong, Tammy Y. N.
    Freisling, Heinz
    Johansson, Mattias
    Lennon, Hannah
    Aune, Dagfinn
    Riboli, Elio
    Trichopoulos, Dimitrios
    Trichopoulou, Antonia
    Tsilidis, Konstantinos K.
    Blood pressure and risk of cancer in the European Prospective Investigation into Cancer and Nutrition2020Ingår i: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 146, nr 10, s. 2680-2693Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Several studies have reported associations of hypertension with cancer, but not all results were conclusive. We examined the association of systolic (SBP) and diastolic (DBP) blood pressure with the development of incident cancer at all anatomical sites in the European Prospective Investigation into Cancer and Nutrition (EPIC). Hazard ratios (HRs) (95% confidence intervals) were estimated using multivariable Cox proportional hazards models, stratified by EPIC-participating center and age at recruitment, and adjusted for sex, education, smoking, body mass index, physical activity, diabetes and dietary (in women also reproductive) factors. The study included 307,318 men and women, with an average follow-up of 13.7 (standard deviation 4.4) years and 39,298 incident cancers. We confirmed the expected positive association with renal cell carcinoma: HR = 1.12 (1.08-1.17) per 10 mm Hg higher SBP and HR = 1.23 (1.14-1.32) for DBP. We additionally found positive associations for esophageal squamous cell carcinoma (SCC): HR = 1.16 (1.07-1.26) (SBP), HR = 1.31 (1.13-1.51) (DBP), weaker for head and neck cancers: HR = 1.08 (1.04-1.12) (SBP), HR = 1.09 (1.01-1.17) (DBP) and, similarly, for skin SCC, colon cancer, postmenopausal breast cancer and uterine adenocarcinoma (AC), but not for esophageal AC, lung SCC, lung AC or uterine endometroid cancer. We observed weak inverse associations of SBP with cervical SCC: HR = 0.91 (0.82-1.00) and lymphomas: HR = 0.97 (0.93-1.00). There were no consistent associations with cancers in other locations. Our results are largely compatible with published studies and support weak associations of blood pressure with cancers in specific locations and morphologies.

  • 18. Christakoudi, Sofia
    et al.
    Pagoni, Panagiota
    Ferrari, Pietro
    Cross, Amanda J.
    Tzoulaki, Ioanna
    Muller, David C.
    Weiderpass, Elisabete
    Freisling, Heinz
    Murphy, Neil
    Dossus, Laure
    Turzanski Fortner, Renee
    Agudo, Antonio
    Overvad, Kim
    Perez-Cornago, Aurora
    Key, Timothy J.
    Brennan, Paul
    Johansson, Mattias
    Tjønneland, Anne
    Halkjær, Jytte
    Boutron-Ruault, Marie-Christine
    Artaud, Fanny
    Severi, Gianluca
    Kaaks, Rudolf
    Schulze, Matthias B.
    Bergmann, Manuela M.
    Masala, Giovanna
    Grioni, Sara
    Simeon, Vittorio
    Tumino, Rosario
    Sacerdote, Carlotta
    Skeie, Guri
    Rylander, Charlotta
    Borch, Kristin Benjaminsen
    Quirós, J. Ramón
    Rodriguez-Barranco, Miguel
    Chirlaque, Maria-Dolores
    Ardanaz, Eva
    Amiano, Pilar
    Drake, Isabel
    Stocks, Tanja
    Häggström, Christel
    Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning. Department of Surgical Science, Uppsala University, Uppsala, Sweden.
    Harlid, Sophia
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Ellingjord-Dale, Merete
    Riboli, Elio
    Tsilidis, Konstantinos K.
    Weight change in middle adulthood and risk of cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort2021Ingår i: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 148, nr 7, s. 1637-1651Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Obesity is a risk factor for several major cancers. Associations of weight change in middle adulthood with cancer risk, however, are less clear. We examined the association of change in weight and body mass index (BMI) category during middle adulthood with 42 cancers, using multivariable Cox proportional hazards models in the European Prospective Investigation into Cancer and Nutrition cohort. Of 241 323 participants (31% men), 20% lost and 32% gained weight (>0.4 to 5.0 kg/year) during 6.9 years (average). During 8.0 years of follow-up after the second weight assessment, 20 960 incident cancers were ascertained. Independent of baseline BMI, weight gain (per one kg/year increment) was positively associated with cancer of the corpus uteri (hazard ratio [HR] = 1.14; 95% confidence interval: 1.05-1.23). Compared to stable weight (+/- 0.4 kg/year), weight gain (>0.4 to 5.0 kg/year) was positively associated with cancers of the gallbladder and bile ducts (HR = 1.41; 1.01-1.96), postmenopausal breast (HR = 1.08; 1.00-1.16) and thyroid (HR = 1.40; 1.04-1.90). Compared to maintaining normal weight, maintaining overweight or obese BMI (World Health Organisation categories) was positively associated with most obesity-related cancers. Compared to maintaining the baseline BMI category, weight gain to a higher BMI category was positively associated with cancers of the postmenopausal breast (HR = 1.19; 1.06-1.33), ovary (HR = 1.40; 1.04-1.91), corpus uteri (HR = 1.42; 1.06-1.91), kidney (HR = 1.80; 1.20-2.68) and pancreas in men (HR = 1.81; 1.11-2.95). Losing weight to a lower BMI category, however, was inversely associated with cancers of the corpus uteri (HR = 0.40; 0.23-0.69) and colon (HR = 0.69; 0.52-0.92). Our findings support avoiding weight gain and encouraging weight loss in middle adulthood.

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  • 19. Costas, Laura
    et al.
    Lujan-Barroso, Leila
    Benavente, Yolanda
    Allen, Naomi E.
    Amiano, Pilar
    Ardanaz, Eva
    Besson, Caroline
    Boeing, Heiner
    Bueno-de-Mesquita, Bas
    Cervenka, Iris
    Fortner, Renee T.
    Fournier, Agnes
    Gunter, Marc
    Harlid, Sophia
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Maria Huerta, Jose
    Jerkeman, Mats
    Jirstrom, Karin
    Kaaks, Rudolf
    Karakatsani, Anna
    Khaw, Kay-Tee
    Kotanidou, Anastasia
    Lund, Eiliv
    Masala, Giovanna
    Mattiello, Amalia
    Melin, Beatrice S.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Menendez, Virginia
    Murphy, Neil
    Nieters, Alexandra
    Overvad, Kim
    Riboli, Elio
    Sacerdote, Carlotta
    Sanchez, Maria-Jose
    Schmidt, Julie A.
    Sieri, Sabina
    Tjonneland, Anne
    Trichopoulou, Antonia
    Tumino, Rosario
    Vermeulen, Roel
    Weiderpass, Elisabete
    de Sanjose, Silvia
    Agudo, Antonio
    Casabonne, Delphine
    Reproductive Factors, Exogenous Hormone Use, and Risk of B-Cell Non-Hodgkin Lymphoma in a Cohort of Women From the European Prospective Investigation Into Cancer and Nutrition2019Ingår i: American Journal of Epidemiology, ISSN 0002-9262, E-ISSN 1476-6256, Vol. 188, nr 2, s. 274-281Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The role of hormonal factors in the etiology of lymphoid neoplasms remains unclear. Previous studies have yielded conflicting results, have lacked sufficient statistical power to assess many lymphoma subtypes, or have lacked detailed information on relevant exposures. Within the European Prospective Investigation Into Cancer and Nutrition cohort, we analyzed comprehensive data on reproductive factors and exogenous hormone use collected at baseline (1992-2000) among 343,458 women, including data on 1,427 incident cases of B-cell non-Hodgkin lymphoma (NHL) and its major subtypes identified after a mean follow-up period of 14 years (through 2015). We estimated hazard ratios and 95% confidence intervals using multivariable proportional hazards modeling. Overall, we observed no statistically significant associations between parity, age at first birth, breastfeeding, oral contraceptive use, or ever use of postmenopausal hormone therapy and risk of B-cell NHL or its subtypes. Women who had undergone surgical menopause had a 51% higher risk of B-cell NHL (based on 67 cases) than women with natural menopause (hazard ratio = 1.51, 95% confidence interval: 1.17, 1.94). Given that this result may have been due to chance, our results provide little support for the hypothesis that sex hormones play a role in lymphomagenesis.

  • 20.
    Dam, Veerle
    et al.
    Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands; Netherlands Heart Institute, Utrecht, Netherlands.
    Onland-Moret, N. Charlotte
    Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands.
    Burgess, Stephen
    MRC Biostatistics Unit, University of Cambridge, Cambridge, United Kingdom; MRC/BHF Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom; Homerton College, Cambridge, United Kingdom.
    Chirlaque, Maria-Dolores
    Department of Epidemiology, Regional Health Authority, IMIB-Arrixaca, Murcia University, Murcia, Spain.
    Peters, Sanne A. E
    Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands; The George Institute for Global Health, Imperial College London, London, United Kingdom.
    Schuit, Ewoud
    Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands.
    Tikk, Kaja
    Division of Clinical Epidemiology and Aging Research, German Cancer Research Centre (DKFZ), Heidelberg, Germany; German Cancer Consortium, DKFZ, Heidelberg, Germany.
    Weiderpass, Elisabete
    International Agency for Research on Cancer, World Health Organization, Lyon, France.
    Oliver-Williams, Clare
    MRC/BHF Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom; Homerton College, Cambridge, United Kingdom.
    Wood, Angela M
    MRC/BHF Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom.
    Tjønneland, Anne
    Danish Cancer Society Research Center, Copenhagen, Denmark; Department of Public Health, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
    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.
    Boutron-Ruault, Marie-Christine
    INSERM, Centre for Research in Epidemiology and Population Health, U1018, Nutrition, Hormones, and Women's Health Team, Institut Gustave Roussy, Villejuif, France.
    Schulze, Matthias B
    Department of Epidemiology, German Institute of Human Nutrition, Potsdam-Rehbruecke, Nuthetal, Germany; Institute of Nutritional Science, University of Potsdam, Nuthetal, Germany.
    Trichopoulou, Antonia
    Hellenic Health Foundation, Athens, Greece; WHO Collaborating Center for Nutrition and Health, Unit of Nutritional Epidemiology and Nutrition in Public Health, Department of Hygiene, Epidemiology and Medical Statistics, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.
    Ferrari, Pietro
    International Agency for Research on Cancer, World Health Organization, Lyon, France.
    Masala, Giovanna
    Cancer Risk Factors and Life-Style Epidemiology Unit, Institute for Cancer Research, Prevention and Clinical Network - ISPRO, Florence, Italy.
    Krogh, Vittorio
    Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
    Tumino, Rosario
    Cancer Registry and Histopathology Department, "Civic - M.P. Arezzo" hospital, ASP Ragusa, Ragusa, Italy.
    Matullo, Giuseppe
    Department of Medical Sciences, University of Torino, Torino, Italy; Italian Institute for Genomic Medicine–IIGM/HuGeF, Torino, Italy.
    Panico, Salvatore
    Dipartimento di medicina clinica e chirurgia, Federico II University, Naples, Italy.
    Boer, Jolanda M. A
    National Institute for Public Health and the Environment, Bilthoven, Netherlands.
    Verschuren, W. M. Monique
    Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands; National Institute for Public Health and the Environment, Bilthoven, Netherlands.
    Waaseth, Marit
    Department of Pharmacy, Faculty of Health Sciences, UiT the Arctic University of Norway, Tromsø, Norway.
    PCrossed D sign©rez, Maria JosCrossed D sign© Sánchez
    Escuela Andaluza de Salud Pública. Instituto de Investigación Biosanitaria ibs.GRANADA, Universidad de Granada, Granada, Spain; CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain.
    Amiano, Pilar
    CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain; Public Health Division of Gipuzkoa, Biodonostia Research Institute, San Sebastian, Spain.
    Imaz, Liher
    CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain; Public Health Division of Gipuzkoa, Biodonostia Research Institute, San Sebastian, Spain.
    Moreno-Iribas, Conchi
    Instituto de Salud Pública de Navarra, IdiSNA, Navarre Institute for Health Research, REDISSEC, Pamplona, Spain.
    Melander, Olle
    Department of Clinical Sciences, Lund University, Malmö, Sweden.
    Harlid, Sophia
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Nordendahl, Maria
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi. Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Wennberg, Patrik
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Key, Timothy J
    Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.
    Riboli, Elio
    Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom.
    Santiuste, Carmen
    CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain; Department of Epidemiology, Murcia Regional Health Authority, IMIB-Arrixaca, Murcia, Spain.
    Kaaks, Rudolf
    Division of Cancer Epidemiology, DKFZ, Foundation under Public Law, Heidelberg, Germany.
    Katzke, Verena
    Division of Cancer Epidemiology, DKFZ, Foundation under Public Law, Heidelberg, Germany.
    Langenberg, Claudia
    MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Cambridge, United Kingdom.
    Wareham, Nicholas J
    MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Cambridge, United Kingdom.
    Schunkert, Heribert
    Deutsches Herzzentrum München, Technische Universität München, Munich, Germany; DZHK (German Center for Cardiovascular Research), Partner Site Munich Heart Alliance, Munich, Germany.
    Erdmann, Jeanette
    Institute for Cardiogenetics, University of Lübeck, Lübeck, Germany.
    Willenborg, Christina
    Institute for Cardiogenetics, University of Lübeck, Lübeck, Germany.
    Hengstenberg, Christian
    Department of Internal Medicine II, Division of Cardiology, Medical University of Vienna, Vienna, Austria.
    Kleber, Marcus E
    Vth Department of Medicine, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
    Delgado, Graciela
    Vth Department of Medicine, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
    März, Winfried
    Vth Department of Medicine, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany; Synlab Academy, Synlab Holding Deutschland GmbH, Mannheim, Germany; Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria.
    Kanoni, Stavroula
    William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom.
    Dedoussis, George
    Department of Nutrition-Dietetics/Harokopio University, Athens, Greece.
    Deloukas, Panos
    William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom; Centre for Genomic Health, Queen Mary University of London, London, United Kingdom; Princess Al-Jawhara Al-Brahim Centre of Excellence in Research of Hereditary Disorders, King Abdulaziz University, Jeddah, Saudi Arabia.
    Nikpay, Majid
    Ruddy Canadian Cardiovascular Genetics Centre, University of Ottawa Heart Institute, ON, Ottawa, Canada.
    Mcpherson, Ruth
    Ruddy Canadian Cardiovascular Genetics Centre, University of Ottawa Heart Institute, ON, Ottawa, Canada.
    Scholz, Markus
    Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany; LIFE Research Center for Civilization Diseases, University of Leipzig, Leipzig, Germany.
    Teren, Andrej
    LIFE Research Center for Civilization Diseases, University of Leipzig, Leipzig, Germany; Heart Center Leipzig, Leipzig, Germany.
    Butterworth, Adam S
    MRC/BHF Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom.
    Van Der Schouw, Yvonne T
    Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands.
    Genetically Determined Reproductive Aging and Coronary Heart Disease: A Bidirectional 2-sample Mendelian Randomization2022Ingår i: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 107, nr 7, s. E2952-E2961Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Accelerated reproductive aging, in women indicated by early natural menopause, is associated with increased coronary heart disease (CHD) risk in observational studies. Conversely, an adverse CHD risk profile has been suggested to accelerate menopause. Objectives: To study the direction and evidence for causality of the relationship between reproductive aging and (non-)fatal CHD and CHD risk factors in a bidirectional Mendelian randomization (MR) approach, using age at natural menopause (ANM) genetic variants as a measure for genetically determined reproductive aging in women. We also studied the association of these variants with CHD risk (factors) in men. Design: Two-sample MR, using both cohort data as well as summary statistics, with 4 methods: simple and weighted median-based, standard inverse-variance weighted (IVW) regression, and MR-Egger regression. Participants: Data from EPIC-CVD and summary statistics from UK Biobank and publicly available genome-wide association studies were pooled for the different analyses. Main Outcome Measures: CHD, CHD risk factors, and ANM. Results: Across different methods of MR, no association was found between genetically determined reproductive aging and CHD risk in women (relative risk estimateIVW = 0.99; 95% confidence interval (CI), 0.97-1.01), or any of the CHD risk factors. Similarly, no associations were found in men. Neither did the reversed analyses show evidence for an association between CHD (risk factors) and reproductive aging. Conclusion: Genetically determined reproductive aging is not causally associated with CHD risk (factors) in women, nor were the genetic variants associated in men. We found no evidence for a reverse association in a combined sample of women and men.

  • 21.
    Dimou, Niki
    et al.
    Section of Nutrition and Metabolism, International Agency for Research on Cancer, Lyon, France.
    Mori, Nagisa
    Section of Nutrition and Metabolism, International Agency for Research on Cancer, Lyon, France.
    Harlid, Sophia
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Harbs, Justin
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Martin, Richard M.
    MRC Integrative Epidemiology Unit (IEU), Bristol Medical School, University of Bristol, Bristol, United Kingdom; Department of Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom; National Institute for Health Research (NIHR) Bristol Biomedical Research Centre, University Hospitals Bristol NHS Foundation Trust and the University of Bristol, Bristol, United Kingdom.
    Smith-Byrne, Karl
    Genetic Epidemiology Group, International Agency for Research on Cancer, Lyon, France.
    Papadimitriou, Nikos
    Section of Nutrition and Metabolism, International Agency for Research on Cancer, Lyon, France.
    Timothy Bishop, D.
    Leeds Institute of Medical Research at St James's, University of Leeds, Leeds, United Kingdom.
    Casey, Graham
    Center for Public Health Genomics, University of Virginia, VA, Charlottesville, United States.
    Colorado-Yohar, Sandra M.
    Department of Epidemiology, Murcia Regional Health Council, IMIBArrixaca, Murcia, Spain; CIBER Epidemiología y Salud Publica (CIBERESP), Spain; Research Group on Demography and Health, National Faculty of Public Health, University of Antioquia, Medellín, Colombia.
    Cotterchio, Michelle
    Ontario Health (Cancer Care Ontario), ON, Toronto, Canada; Dalla Lana School of Public Health, University of Toronto, ON, Toronto, Canada.
    Cross, Amanda J.
    Department of Epidemiology and Biostatistics, Imperial College London, Norfolk Place, London, United Kingdom.
    Le Marchand, Loic
    University of Hawaii Cancer Center, HI, Honolulu, United States.
    Lin, Yi
    Public Health Sciences Division, Fred Hutchinson Cancer Research Center, 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.
    Charlotte Onland-Moret, N.
    Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, Netherlands.
    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.
    Potter, John D.
    Public Health Sciences Division, Fred Hutchinson Cancer Research Center, WA, Seattle, United States; Department of Epidemiology, University of Washington, WA, Seattle, United States; Centre for Public Health Research, Massey University, Wellington, New Zealand.
    Rohan, Thomas E.
    Department of Epidemiology and Population Health, Albert Einstein College of Medicine, NY, Bronx, United States.
    Weiderpass, Elisabete
    Office of the Director, International Agency for Research on Cancer, 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.
    Circulating levels of testosterone, sex hormone binding globulin and colorectal cancer risk: Observational and mendelian randomization analyses2021Ingår i: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 30, nr 7, s. 1336-1348Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Epidemiologic studies evaluating associations between sex steroid hormones and colorectal cancer risk have yielded inconsistent results. To elucidate the role of circulating levels of testosterone, and sex hormone-binding globulin (SHBG) in colorectal cancer risk, we conducted observational and Mendelian randomization (MR) analyses.

    Methods: The observational analyses included 333,530 participants enrolled in the UK Biobank with testosterone and SHBG measured. HRs and 95% confidence intervals (CI) were estimated using multivariable Cox proportional hazards models. For MR analyses, genetic variants robustly associated with hormone levels were identified and their association with colorectal cancer (42,866 cases/42,752 controls) was examined using two-sample MR.

    Results: In the observational analysis, there was little evidence that circulating levels of total testosterone were associated with colorectal cancer risk; the MR analyses showed a greater risk for women (OR per 1-SD = 1.09; 95% CI, 1.01-1.17), although pleiotropy may have biased this result. Higher SHBG concentrations were associated with greater colorectal cancer risk for women (HR per 1-SD = 1.16; 95% CI, 1.05-1.29), but was unsupported by the MR analysis. There was little evidence of associations between free testosterone and colorectal cancer in observational andMRanalyses.

    Conclusions: Circulating concentrations of sex hormones are unlikely to be causally associated with colorectal cancer. Additional experimental studies are required to better understand the possible role of androgens in colorectal cancer development.

  • 22.
    Dimou, Niki
    et al.
    Nutrition and Metabolism Branch, International Agency for Research on Cancer, Lyon, France.
    Omiyale, Wemimo
    Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.
    Biessy, Carine
    Nutrition and Metabolism Branch, International Agency for Research on Cancer, Lyon, France.
    Viallon, Vivian
    Nutrition and Metabolism Branch, International Agency for Research on Cancer, Lyon, France.
    Kaaks, Rudolf
    Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
    O'Mara, Tracy A.
    Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, QLD, Brisbane, Australia.
    Aglago, Elom K.
    Nutrition and Metabolism Branch, International Agency for Research on Cancer, Lyon, France.
    Ardanaz, Eva
    Navarra Public Health Institute, Pamplona, Spain; IdiSNA, Navarra Institute for Health Research, Pamplona, Spain; CIBER Epidemiología y Salud Pública (CIBERESP), Spain.
    Bergmann, Manuela M.
    German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal, Germany.
    Bondonno, Nicola P.
    Danish Cancer Society Research Center, Copenhagen, Denmark.
    Braaten, Tonje
    Department of Community Medicine, Faculty of Health Sciences, UiT The Arctic University of Norway, Tromsø, Norway.
    Colorado-Yohar, Sandra M.
    CIBER Epidemiología y Salud Pública (CIBERESP), 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.
    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. Boston, MA, United States.
    Dahm, Christina C.
    Department of Public Health, Aarhus University, Aarhus, Denmark.
    Fortner, Renée T
    Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
    Gram, Inger T.
    Department of Community Medicine, Faculty of Health Sciences, UiT The Arctic University of Norway, Tromsø, Norway.
    Harlid, Sophia
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Heath, Alicia K.
    Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom.
    Idahl, Annika
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Kvaskoff, Marina
    UVSQ, Inserm CESP U1018, Gustave Roussy, Université Paris-Saclay, Villejuif, France.
    Nøst, Therese H.
    Department of Community Medicine, Faculty of Health Sciences, UiT The Arctic University of Norway, Tromsø, Norway; K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Trondheim, Norway.
    Overvad, Kim
    Department of Public Health, Aarhus University, Aarhus, Denmark.
    Palli, Domenico
    Cancer Risk Factors and Life-Style Epidemiology Unit, Institute for Cancer Research, Prevention and Clinical Network (ISPRO), Florence, Italy.
    Perez-Cornago, Aurora
    Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.
    Sacerdote, Carlotta
    Unit of Cancer Epidemiology, Città della Salute e della Scienza University-Hospital, Turin, Italy.
    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.
    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.
    Severi, Gianluca
    UVSQ, Inserm CESP U1018, Gustave Roussy, Université Paris-Saclay, Villejuif, France; Department of Statistics, Computer Science, Applications "G. Parenti", University of Florence, Florence, Italy.
    Simeon, Vittorio
    Dipartimento di Salute Mentale e Fisica e Medicina Preventiva, University of Naples "L. Vanvitelli", Naples, Italy.
    Tagliabue, Giovanna
    Department of Research, Fondazione IRCCS Istituto Nazionale dei Tumori Via Venezian 1, Milan, Italy.
    Tjønneland, Anne
    Department of Public Health, University of Copenhagen, Copenhagen, Denmark.
    Truong, Thérèse
    UVSQ, Inserm CESP U1018, Gustave Roussy, Université Paris-Saclay, Villejuif, France.
    Tumino, Rosario
    Hyblean Association for Epidemiological Research, Ragusa, Italy.
    Johansson, Mattias
    Section of Genetics, International Agency for Research on Cancer, Lyon, France.
    Weiderpass, Elisabete
    Office of the Director, International Agency for Research on Cancer, World Health Organization, Lyon, France.
    Murphy, Neil
    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.
    Lacey, Ben
    Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.
    Allen, Naomi E.
    Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.
    Dossus, Laure
    Nutrition and Metabolism Branch, International Agency for Research on Cancer, Lyon, France.
    Cigarette Smoking and Endometrial Cancer Risk: observational and Mendelian Randomization Analyses2022Ingår i: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 31, nr 9, s. 1839-1848Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Current epidemiologic evidence indicates that smoking is associated with a lower endometrial cancer risk. However, it is unknown if this association is causal or confounded. To further elucidate the role of smoking in endometrial cancer risk, we conducted complementary observational and Mendelian randomization (MR) analyses.

    METHODS: The observational analyses included 286,415 participants enrolled in the European Prospective Investigation into Cancer and Nutrition and 179,271 participants in the UK Biobank, and multivariable Cox proportional hazards models were used. In two-sample MR analyses, genetic variants robustly associated with lifetime amount of smoking (n = 126 variants) and ever having smoked regularly (n = 112 variants) were selected and their association with endometrial cancer risk (12,906 cancer/108,979 controls from the Endometrial Cancer Association Consortium) was examined.

    RESULTS: In the observational analysis, lifetime amount of smoking and ever having smoked regularly were associated with a lower endometrial cancer risk. In the MR analysis accounting for body mass index, a genetic predisposition to a higher lifetime amount of smoking was not associated with endometrial cancer risk (OR per 1-SD increment: 1.15; 95% confidence interval: 0.91-1.44). Genetic predisposition to ever having smoked regularly was not associated with risk of endometrial cancer.

    CONCLUSIONS: Smoking was inversely associated with endometrial cancer in the observational analyses, although unsupported by the MR. Additional studies are required to better understand the possible confounders and mechanisms underlying the observed associations between smoking and endometrial cancer. IMPACT: The results from this analysis indicate that smoking is unlikely to be causally linked with endometrial cancer risk.

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  • 23. Fedirko, Veronika
    et al.
    Jenab, Mazda
    Meplan, Catherine
    Jones, Jeb S.
    Zhu, Wanzhe
    Schomburg, Lutz
    Siddiq, Afshan
    Hybsier, Sandra
    Overvad, Kim
    Tjonneland, Anne
    Omichessan, Hanane
    Perduca, Vittorio
    Boutron-Ruault, Marie-Christine
    Kuehn, Tilman
    Katzke, Verena
    Aleksandrova, Krasimira
    Trichopoulou, Antonia
    Karakatsani, Anna
    Kotanidou, Anastasia
    Tumino, Rosario
    Panico, Salvatore
    Masala, Giovanna
    Agnoli, Claudia
    Naccarati, Alessio
    Bueno-de-Mesquita, Bas
    Vermeulen, Roel C. H.
    Weiderpass, Elisabete
    Skeie, Guri
    Nost, Therese Haugdahl
    Lujan-Barroso, Leila
    Ramon Quiros, J.
    Maria Huerta, Jose
    Rodriguez-Barranco, Miguel
    Barricarte, Aurelio
    Gylling, Björn
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Harlid, Sophia
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Bradbury, Kathryn E.
    Wareham, Nick
    Khaw, Kay-Tee
    Gunter, Marc
    Murphy, Neil
    Freisling, Heinz
    Tsilidis, Kostas
    Aune, Dagfinn
    Riboli, Elio
    Hesketh, John E.
    Hughes, David J.
    Association of Selenoprotein and Selenium Pathway Genotypes with Risk of Colorectal Cancer and Interaction with Selenium Status2019Ingår i: Nutrients, E-ISSN 2072-6643, Vol. 11, nr 4, artikel-id 935Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Selenoprotein genetic variations and suboptimal selenium (Se) levels may contribute to the risk of colorectal cancer (CRC) development. We examined the association between CRC risk and genotype for single nucleotide polymorphisms (SNPs) in selenoprotein and Se metabolic pathway genes. Illumina Goldengateassays were designed and resulted in the genotyping of 1040 variants in 154 genes from 1420 cases and 1421 controls within the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Multivariable logistic regression revealed an association of 144 individual SNPs from 63 Se pathway genes with CRC risk. However, regarding the selenoprotein genes, only TXNRD1 rs11111979 retained borderline statistical significance after adjustment for correlated tests (PACT = 0.10; PACT significance threshold was P < 0.1). SNPs in Wingless/Integrated (Wnt) and Transforming growth factor (TGF) beta-signaling genes (FRZB, SMAD3, SMAD7) from pathways affected by Se intake were also associated with CRC risk after multiple testing adjustments. Interactions with Se status (using existing serum Se and Selenoprotein P data) were tested at the SNP, gene, and pathway levels. Pathway analyses using the modified Adaptive Rank Truncated Product method suggested that genes and gene x Se status interactions in antioxidant, apoptosis, and TGF-beta signaling pathways may be associated with CRC risk. This study suggests that SNPs in the Se pathway alone or in combination with suboptimal Se status may contribute to CRC development.

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  • 24. Fedirko, Veronika
    et al.
    Mandle, Hannah B.
    Zhu, Wanzhe
    Hughes, David J.
    Siddiq, Afshan
    Ferrari, Pietro
    Romieu, Isabelle
    Riboli, Elio
    Bueno-de-Mesquita, Bas
    van Duijnhoven, Franzel J. B.
    Siersema, Peter D.
    Tjonneland, Anne
    Olsen, Anja
    Perduca, Vittorio
    Carbonnel, Franck
    Boutron-Ruault, Marie-Christine
    Kuehn, Tilman
    Johnson, Theron
    Krasimira, Aleksandrova
    Trichopoulou, Antonia
    Makrythanasis, Periklis
    Thanos, Dimitris
    Panico, Salvatore
    Krogh, Vittorio
    Sacerdote, Carlotta
    Skeie, Guri
    Weiderpass, Elisabete
    Colorado-Yohar, Sandra
    Sala, Nuria
    Barricarte, Aurelio
    Sanchez, Maria-Jose
    Quiros, Ramon
    Amiano, Pilar
    Gylling, Björn
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Harlid, Sophia
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Perez-Cornago, Aurora
    Heath, Alicia K.
    Tsilidis, Konstantinos K.
    Aune, Dagfinn
    Freisling, Heinz
    Murphy, Neil
    Gunter, Marc J.
    Jenab, Mazda
    Vitamin D-Related Genes, Blood Vitamin D Levels and Colorectal Cancer Risk in Western European Populations2019Ingår i: Nutrients, E-ISSN 2072-6643, Vol. 11, nr 8, artikel-id 1954Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Higher circulating 25-hydroxyvitamin D levels (25(OH)D) have been found to be associated with lower risk for colorectal cancer (CRC) in prospective studies. Whether this association is modified by genetic variation in genes related to vitamin D metabolism and action has not been well studied in humans. We investigated 1307 functional and tagging single-nucleotide polymorphisms (SNPs; individually, and by gene/pathway) in 86 vitamin D-related genes in 1420 incident CRC cases matched to controls from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. We also evaluated the association between these SNPs and circulating 25(OH)D in a subset of controls. We confirmed previously reported CRC risk associations between SNPs in the VDR, GC, and CYP27B1 genes. We also identified additional associations with 25(OH)D, as well as CRC risk, and several potentially novel SNPs in genes related to vitamin D transport and action (LRP2, CUBN, NCOA7, and HDAC9). However, none of these SNPs were statistically significant after Benjamini-Hochberg (BH) multiple testing correction. When assessed by a priori defined functional pathways, tumor growth factor beta (TGF beta) signaling was associated with CRC risk (P <= 0.001), with most statistically significant genes being SMAD7 (P-BH = 0.008) and SMAD3 (P-BH = 0.008), and 18 SNPs in the vitamin D receptor (VDR) binding sites (P = 0.036). The 25(OH)D-gene pathway analysis suggested that genetic variants in the genes related to VDR complex formation and transcriptional activity are associated with CRC depending on 25(OH)D levels (interaction P = 0.041). Additional studies in large populations and consortia, especially with measured circulating 25(OH)D, are needed to confirm our findings.

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  • 25.
    Fiolet, Thibault
    et al.
    Paris-Saclay University, UVSQ, Univ. Paris-Sud, Inserm, Gustave Roussy, “Exposome and Heredity” Team, CESP, Villejuif, France.
    Casagrande, Corinne
    Nutrition and Metabolism Branch, International Agency for Research on Cancer, 150 cours Albert Thomas, CEDEX 08, Lyon, France.
    Nicolas, Geneviève
    Nutrition and Metabolism Branch, International Agency for Research on Cancer, 150 cours Albert Thomas, CEDEX 08, Lyon, France.
    Horvath, Zsuzsanna
    European Food Safety Authority, Via Carlo Magno 1A, Parma, Italy.
    Frenoy, Pauline
    Paris-Saclay University, UVSQ, Univ. Paris-Sud, Inserm, Gustave Roussy, “Exposome and Heredity” Team, CESP, Villejuif, France.
    Weiderpass, Elisabete
    International Agency for Research on Cancer, 150 cours Albert Thomas, CEDEX 08, Lyon, France.
    Katzke, Verena
    Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
    Kaaks, Rudolf
    Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
    Rodriguez-Barranco, Miguel
    Escuela Andaluza de Salud Pública (EASP), Granada, Spain; Instituto de Investigación Biosanitaria ibs.GRANADA, Granada, Spain; Spanish Consortium for Research on Epidemiology and Public Health (CIBERESP), Madrid, Spain.
    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, Via Santena 7, Turin, Italy.
    Manjer, Jonas
    Dept Surgery, Skåne University Hospital Malmö, Lund University, Malmö, Sweden.
    Sonestedt, Emily
    Nutritional Epidemiology, Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden.
    Grioni, Sara
    Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Via Venezian, 1, Milano, Italy.
    Agudo, Antonio
    Unit of Nutrition and Cancer, Catalan Institute of Oncology - ICO, L'Hospitalet de Llobregat, Spain., Nutrition and Cancer Group, Epidemiology, Public Health, Cancer Prevention and Palliative Care Program, Bellvitge Biomedical Research Institute - IDIBELL, L'Hospitalet de Llobregat, Spain.
    Rylander, Charlotta
    Department of Community Medicine, Faculty of Health Sciences, University of Tromsø (UiT), The Arctic University of Norway, Tromsø, Norway.
    Haugdahl Nøst, Therese
    Department of Community Medicine, Faculty of Health Sciences, University of Tromsø (UiT), The Arctic University of Norway, Tromsø, Norway.
    Skeie, Guri
    Department of Community Medicine, Faculty of Health Sciences, University of Tromsø (UiT), The Arctic University of Norway, Tromsø, Norway.
    Tjønneland, Anne
    Danish Cancer Society Research Center, Copenhagen, Denmark; Department of Public Health, University of Copenhagen, Denmark.
    Raaschou-Nielsen, Ole
    Danish Cancer Society Research Center, Copenhagen, Denmark; Department of Environmental Science, Aarhus University, Roskilde, Denmark.
    Ardanaz, Eva
    Spanish Consortium for Research on Epidemiology and Public Health (CIBERESP), Madrid, Spain; Navarra Public Health Institute, Pamplona, Spain; IdiSNA, Navarra Institute for Health Research, Pamplona, Spain.
    Amiano, Pilar
    Spanish Consortium for Research on Epidemiology and Public Health (CIBERESP), Madrid, Spain; Ministry of Health of the Basque Government, Sub-Directorate for Public Health and Addictions of Gipuzkoa, Biodonostia Health Research Institute, Group of Epidemiology of Chronic and Communicable Diseases, San Sebastián, Spain.
    Dolores Chirlaque López, María
    Spanish Consortium for Research on Epidemiology and Public Health (CIBERESP), Madrid, Spain; Department of Epidemiology, Regional Health Council, IMIB-Arrixaca, Murcia University, Murcia, Spain.
    Schulze, Matthias B.
    Department of Molecular Epidemiology, Germen Institute of Human Nutrition, Potsdam-Rehruecke, Nuthetal, Germany; Institute of Nutritional Science, University of Potsdam, Potsdam, Germany.
    Wennberg, Maria
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för hållbar hälsa.
    Harlid, Sophia
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Cairat, Manon
    Paris-Saclay University, UVSQ, Univ. Paris-Sud, Inserm, Gustave Roussy, “Exposome and Heredity” Team, CESP, Villejuif, France; Nutrition and Metabolism Branch, International Agency for Research on Cancer, 150 cours Albert Thomas, CEDEX 08, Lyon, France.
    Kvaskoff, Marina
    Paris-Saclay University, UVSQ, Univ. Paris-Sud, Inserm, Gustave Roussy, “Exposome and Heredity” Team, CESP, Villejuif, France.
    Huybrechts, Inge
    Nutrition and Metabolism Branch, International Agency for Research on Cancer, 150 cours Albert Thomas, CEDEX 08, Lyon, France.
    Romana Mancini, Francesca
    Paris-Saclay University, UVSQ, Univ. Paris-Sud, Inserm, Gustave Roussy, “Exposome and Heredity” Team, CESP, Villejuif, France.
    Dietary intakes of dioxins and polychlorobiphenyls (PCBs) and breast cancer risk in 9 European countries2022Ingår i: Environment International, ISSN 0160-4120, E-ISSN 1873-6750, Vol. 163, artikel-id 107213Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Dioxins and polychlorobiphenyls (PCBs) are persistent organic pollutants that have demonstrated endocrine disrupting properties. Several of these chemicals are carcinogenic and positive associations have been suggested with breast cancer risk. In general population, diet represents the main source of exposure.

    Methods: Associations between dietary intake of 17 dioxins and 35 PCBs and breast cancer were evaluated in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort from nine European countries using multivariable Cox regressions. The present study included 318,607 women (mean ± SD age: 50.7 ± 9.7) with 13,241 incident invasive breast cancers and a median follow-up of 14.9 years (IQR = 13.5–16.4). Dietary intake of dioxins and PCBs was assessed combining EPIC food consumption data with food contamination data provided by the European Food Safety Authority.

    Results: Exposure to dioxins, dioxins + Dioxin-Like-PCBs, Dioxin-Like-PCBs (DL-PCBs), and Non-Dioxin-Like-PCBs (NDL-PCBs) estimated from reported dietary intakes were not associated with breast cancer incidence, with the following hazard ratios (HRs) and 95% confidence intervals for an increment of 1 SD: HRdioxins = 1.00 (0.98 to 1.02), HRdioxins+DL-PCB = 1.01 (0.98 to 1.03), HRDL-PCB = 1.01 (0.98 to 1.03), and HRNDL-PCB = 1.01 (0.99 to 1.03). Results remained unchanged when analyzing intakes as quintile groups, as well as when analyses were run separately per country, or separating breast cancer cases based on estrogen receptor status or after further adjustments on main contributing food groups to PCBs and dioxins intake and nutritional factors.

    Conclusions: This large European prospective study does not support the hypothesis of an association between dietary intake of dioxins and PCBs and breast cancer risk.

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  • 26.
    Fritz, Josef
    et al.
    Department of Translational Medicine, Lund University, Malmö, Sweden; Institute of Medical Statistics and Informatics, Medical University of Innsbruck, Innsbruck, Austria.
    Jochems, Sylvia H. J.
    Department of Clinical Sciences Lund, Lund University, Lund, Sweden.
    Bjørge, Tone
    Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway; Cancer Registry of Norway, Oslo, Norway.
    Wood, Angela M.
    Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom.
    Häggström, Christel
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin. Northern Registry Centre.
    Ulmer, Hanno
    Institute of Medical Statistics and Informatics, Medical University of Innsbruck, Innsbruck, Austria; Agency for Preventive and Social Medicine (aks), Bregenz, Austria.
    Nagel, Gabriele
    Agency for Preventive and Social Medicine (aks), Bregenz, Austria; Institute of Epidemiology and Medical Biometry, Ulm University, Ulm, Germany.
    Zitt, Emanuel
    Agency for Preventive and Social Medicine (aks), Bregenz, Austria; Department of Internal Medicine 3, LKH Feldkirch, Feldkirch, Austria; Vorarlberg Institute for Vascular Investigation and Treatment (VIVIT), Feldkirch, Austria.
    Engeland, Anders
    Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway; Department of Chronic Diseases, Norwegian Institute of Public Health, Bergen, Norway.
    Harlid, Sophia
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Drake, Isabel
    Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden.
    Stattin, Pär
    Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
    Stocks, Tanja
    Department of Translational Medicine, Lund University, Malmö, Sweden; Department of Clinical Sciences Lund, Lund University, Lund, Sweden.
    Body mass index, triglyceride-glucose index, and prostate cancer death: a mediation analysis in eight European cohorts2023Ingår i: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Insulin resistance is a hypothesised biological mechanism linking obesity with prostate cancer (PCa) death. Data in support of this hypothesis is limited.

    Methods: We included 259,884 men from eight European cohorts, with 11,760 incident PCa’s and 1784 PCa deaths during follow-up. We used the triglyceride-glucose (TyG) index as indicator of insulin resistance. We analysed PCa cases with follow-up from PCa diagnosis, and the full cohort with follow-up from the baseline cancer-free state, thus incorporating both PCa incidence and death. We calculated hazard ratios (HR) and the proportion of the total effect of body mass index (BMI) on PCa death mediated through TyG index.

    Results: In the PCa-case-only analysis, baseline TyG index was positively associated with PCa death (HR per 1-standard deviation: 1.11, 95% confidence interval (CI); 1.01–1.22), and mediated a substantial proportion of the baseline BMI effect on PCa death (HRtotal effect per 5-kg/m2 BMI: 1.24; 1.14–1.35, of which 28%; 4%–52%, mediated). In contrast, in the full cohort, the TyG index was not associated with PCa death (HR: 1.03; 0.94-1.13), hence did not substantially mediate the effect of BMI on PCa death.

    Conclusions: Insulin resistance could be an important pathway through which obesity accelerates PCa progression to death.

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  • 27. Hair, Brionna Y
    et al.
    Xu, Zongli
    Kirk, Erin L
    Harlid, Sophia
    Epigenetics and Stem Cell Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina, USA.
    Sandhu, Rupninder
    Robinson, Whitney R
    Wu, Michael C
    Olshan, Andrew F
    Conway, Kathleen
    Taylor, Jack A
    Troester, Melissa A
    Body mass index associated with genome-wide methylation in breast tissue.2015Ingår i: Breast Cancer Research and Treatment, ISSN 0167-6806, E-ISSN 1573-7217, Vol. 151, nr 2, s. 453-63Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Gene expression studies indicate that body mass index (BMI) is associated with molecular pathways involved in inflammation, insulin-like growth factor activation, and other carcinogenic processes in breast tissue. The goal of this study was to determine whether BMI is associated with gene methylation in breast tissue and to identify pathways that are commonly methylated in association with high BMI. Epigenome-wide methylation profiles were determined using the Illumina HumanMethylation450 BeadChip array in the non-diseased breast tissue of 81 women undergoing breast surgery between 2009 and 2013 at the University of North Carolina Hospitals. Multivariable, robust linear regression was performed to identify methylation sites associated with BMI at a false discovery rate q value <0.05. Gene expression microarray data was used to identify which of the BMI-associated methylation sites also showed correlation with gene expression. Gene set enrichment analysis was conducted to assess which pathways were enriched among the BMI-associated methylation sites. Of the 431,568 methylation sites analyzed, 2573 were associated with BMI (q value <0.05), 57 % of which showed an inverse correlation with BMI. Pathways enriched among the 2573 probe sites included those involved in inflammation, insulin receptor signaling, and leptin signaling. We were able to map 1251 of the BMI-associated methylation sites to gene expression data, and, of these, 226 (18 %) showed substantial correlations with gene expression. Our results suggest that BMI is associated with genome-wide methylation in non-diseased breast tissue and may influence epigenetic pathways involved in inflammatory and other carcinogenic processes.

  • 28.
    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)
  • 29.
    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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  • 30.
    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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  • 31.
    Harlid, Sophia
    et al.
    Epigenetics and Stem Cell Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina, USA.
    Adgent, Margaret
    Jefferson, Wendy N.
    Panduri, Vijayalakshmi
    Umbach, David M.
    Xu, Zongli
    Stallings, Virginia A.
    Williams, Carmen J.
    Rogan, Walter J.
    Taylor, Jack A.
    Soy formula and epigenetic modifications: analysis of vaginal epithelial cells from infant girls in the IFED study2017Ingår i: Journal of Environmental Health Perspectives, ISSN 0091-6765, E-ISSN 1552-9924, Vol. 125, nr 3, s. 447-452Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Early-life exposure to estrogenic compounds affects the development of the reproductive system in rodent models and humans. Soy products, which contain phytoestrogens such as genistein, are one source of exposure in infants fed soy formula, and they result in high serum concentrations.

    OBJECTIVES: Our goal was to determine whether soy exposure is associated with differential DNA methylation in vaginal cells from soy-fed infant girls.

    METHODS: Using the Illumina HumanMethylation450 BeadChip, we evaluated epigenome-wide DNA methylation in vaginal cells from four soy formula-fed and six cow formula-fed girls from the Infant Feeding and Early Development (IFED) study. Using pyrosequencing we followed up the two most differentially methylated sites in 214 vaginal cell samples serially collected between birth and 9 months of age from 50 girls (28 soy formula-fed and 22 cow formula-fed). With a mouse model, we examined the effect of neonatal exposure to genistein on gene specific mRNA levels in vaginal tissue.

    RESULTS: The epigenome-wide scan suggested differences in methylation between soy formula-fed and cow formula-fed infants at three CpGs in the gene proline rich 5 like (PRR5L) (p < 10(4)). Pyrosequencing of the two feeding groups found that methylation levels progressively diverged with age, with pointwise differences becoming statistically significant after 126 days. Genistein-exposed mice showed a 50% decrease in vaginal Prr5l mRNA levels compared to controls.

    CONCLUSIONS: Girls fed soy formula have altered DNA methylation in vaginal cell DNA which may be associated with decreased expression of an estrogen-responsive gene.

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  • 32.
    Harlid, Sophia
    et al.
    Lund University, Department of Laboratory Sciences.
    Butt, Salma
    Ivarsson, Malin I L
    Eyfjörd, Jorunn Erla
    Lenner, Per
    Manjer, Jonas
    Dillner, Joakim
    Carlson, Joyce
    Interactive effect of genetic susceptibility with height, body mass index, and hormone replacement therapy on the risk of breast cancer.2012Ingår i: BMC Women's Health, E-ISSN 1472-6874, Vol. 12, artikel-id 17Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Breast cancer today has many established risk factors, both genetic and environmental, but these risk factors by themselves explain only part of the total cancer incidence. We have investigated potential interactions between certain known genetic and phenotypic risk factors, specifically nine single nucleotide polymorphisms (SNPs) and height, body mass index (BMI) and hormone replacement therapy (HRT).

    METHODS: We analyzed samples from three different study populations: two prospectively followed Swedish cohorts and one Icelandic case-control study. Totally 2884 invasive breast cancer cases and 4508 controls were analysed in the study. Genotypes were determined using Mass spectrometry-Maldi-TOF and phenotypic variables were derived from measurements and/or questionnaires. Odds Ratios and 95% confidence intervals were calculated using unconditional logistic regression with the inclusion of an interaction term in the logistic regression model.

    RESULTS: One SNP (rs851987 in ESR1) tended to interact with height, with an increasingly protective effect of the major allele in taller women (p = 0.007) and rs13281615 (on 8q24) tended to confer risk only in non users of HRT (p-for interaction = 0.03). There were no significant interactions after correction for multiple testing.

    CONCLUSIONS: We conclude that much larger sample sets would be necessary to demonstrate interactions between low-risk genetic polymorphisms and the phenotypic variables height, BMI and HRT on the risk for breast cancer. However the present hypothesis-generating study has identified tendencies that would be of interest to evaluate for gene-environment interactions in independent materials.

  • 33.
    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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  • 34.
    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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  • 35.
    Harlid, Sophia
    et al.
    Lund University, Department of Laboratory Sciences.
    Ivarsson, Malin I. L.
    Butt, Salma
    Grzybowska, Eva
    Eyfjord, Jorunn E.
    Lenner, Per
    Forsti, Asta
    Hemminki, Kari
    Manjer, Jonas
    Dillner, Joakim
    Carlson, Joyce
    Combined effect of low-penetrant SNPs on breast cancer risk2012Ingår i: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 106, nr 2, s. 389-396Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Although many low-penetrant genetic risk factors for breast cancer have been discovered, knowledge about the effect of multiple risk alleles is limited, especially in women <50 years. We therefore investigated the association between multiple risk alleles and breast cancer risk as well as individual effects according to age-approximated pre- and post-menopausal status.

    METHODS: Ten previously described breast cancer-associated single-nucleotide polymorphisms (SNPs) were analysed in a joint European biobank-based study comprising 3584 breast cancer cases and 5063 cancer-free controls. Genotyping was performed using MALDI-TOF mass spectrometry, and odds ratios were estimated using logistic regression.

    RESULTS: Significant associations with breast cancer were confirmed for 7 of the 10 SNPs. Analysis of the joint effect of the original 10 as well as the statistically significant 7 SNPs (rs2981582, rs3803662, rs889312, rs13387042, rs13281615, rs3817198 and rs981782) found a highly significant trend for increasing breast cancer risk with increasing number of risk alleles (P-trend 5.6 x 10(-20) and 1.5 x 10(-25), respectively). Odds ratio for breast cancer of 1.84 (95% confidence interval (CI): 1.59-2.14; 10 SNPs) and 2.12 (95% CI: 1.80-2.50; 7 SNPs) was seen for the maximum vs the minimum number of risk alleles. Additionally, one of the examined SNPs (rs981782 in HCN1) had a protective effect that was significantly stronger in premenopausal women (P-value: 7.9 x 10(-4)).

    CONCLUSION: The strongly increasing risk seen when combining many low-penetrant risk alleles supports the polygenic inheritance model of breast cancer. British Journal of Cancer (2012) 106, 389-396. doi:10.1038/bjc.2011.461 www.bjcancer.com Published online 1 November 2011 (C) 2012 Cancer Research UK

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  • 36.
    Harlid, Sophia
    et al.
    Lund University, Department of Laboratory Sciences.
    Ivarsson, Malin I L
    Butt, Salma
    Hussain, Shehnaz
    Grzybowska, Ewa
    Eyfjörd, Jorunn Erla
    Lenner, Per
    Försti, Asta
    Hemminki, Kari
    Manjer, Jonas
    Dillner, Joakim
    Carlson, Joyce
    A candidate CpG SNP approach identifies a breast cancer associated ESR1-SNP2011Ingår i: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 129, nr 7, s. 1689-1698Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Altered DNA methylation is often seen in malignant cells, potentially contributing to carcinogenesis by suppressing gene expression. We hypothesized that heritable methylation potential might be a risk factor for breast cancer and evaluated possible association with breast cancer for single nucleotide polymorphisms (SNPs) either involving CpG sequences in extended 5'-regulatory regions of candidate genes (ESR1, ESR2, PGR, and SHBG) or CpG and missense coding SNPs in genes involved in methylation (MBD1, MECP2, DNMT1, MGMT, MTHFR, MTR, MTRR, MTHFD1, MTHFD2, BHMT, DCTD, and SLC19A1). Genome-wide searches for genetic risk factors for breast cancers have in general not investigated these SNPs, because of low minor allele frequency or weak haplotype associations. Genotyping was performed using Mass spectrometry-Maldi-Tof in a screening panel of 538 cases and 1,067 controls. Potential association to breast cancer was identified for 15 SNPs and one of these SNPs (rs7766585 in ESR1) was found to associate strongly with breast cancer, OR 1.30 (95% CI 1.17-1.45; p-value 2.1 × 10(-6) ), when tested in a verification panel consisting of 3,211 unique breast cancer cases and 4,223 unique controls from five European biobank cohorts. In conclusion, a candidate gene search strategy focusing on methylation-related SNPs did identify a SNP that associated with breast cancer at high significance.

  • 37.
    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)
  • 38.
    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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  • 39.
    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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  • 40.
    Harlid, Sophia
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi. Epigenetics & Stem Cell Biology Laboratory, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, NC, USA.
    Xu, Zongli
    Kirk, Erin
    Wilson, Lauren E.
    Troester, Melissa A.
    Taylor, Jack A.
    Hormone therapy use and breast tissue DNA methylation: analysis of epigenome wide data from the normal breast study2019Ingår i: Epigenetics, ISSN 1559-2294, E-ISSN 1559-2308, Vol. 14, nr 2, s. 146-157Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Hormone therapy (HT) is associated with increased risk of breast cancer, strongly dependent on type, duration, and recency of use. HT use could affect cancer risk by changing breast tissue transcriptional programs. We hypothesize that these changes are preceded by changes in DNA methylation. To explore this hypothesis we used histologically normal-appearing breast tissue from the Normal Breast Study (NBS). DNA methylation β-values were obtained using the Illumina HumanMethylation 450 BeadChips for 90 samples including all NBS-participants who used HT within 5 y before surgery. Data were analyzed using the reference-free cell mixture method. Cancer Genome Atlas (TCGA) mRNA-Seq data were used to assess correlation between DNA methylation and gene expression. We identified 527 CpG sites in 403 genes that were associated with ever using HT at genome wide significance (FDR q < 0.05), of these, 68 sites were also significantly associated with duration of use or recency of use. Twelve sites reached significance in all analyses one of which was cg01382688 in ARHGEF4 (p < 1.2x10-7). Mutations in ARHGEF4 have been reported in breast tumors, but this is the first report of possible breast cancer-related DNA methylation changes. In addition, 22 genes included more than one significant CpG site and a majority of these sites were significantly correlated with gene expression. Although based on small numbers, these findings support the hypothesis that HT is associated with epigenetic alterations in breast tissue, and identifies genes with altered DNA methylation states which could be linked to breast cancer development.

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  • 41.
    Harlid, Sophia
    et al.
    Epigenetics and Stem Cell Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina, USA.
    Xu, Zongli
    Panduri, Vijayalakshmi
    D'Aloisio, Aimee A
    DeRoo, Lisa A
    Sandler, Dale P
    Taylor, Jack A
    In utero exposure to diethylstilbestrol and blood DNA methylation in women ages 40-59 years from the sister study.2015Ingår i: PLOS ONE, E-ISSN 1932-6203, Vol. 10, nr 3, artikel-id e0118757Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    In utero exposure to diethylstilbestrol (DES) has been associated with increased risk of adverse health outcomes such as fertility problems and vaginal as well as breast cancer. Animal studies have linked prenatal DES exposure to lasting DNA methylation changes. We investigated genome-wide DNA methylation and in utero DES exposure in a sample of non-Hispanic white women aged 40-59 years from the Sister Study, a large United States cohort study of women with a family history of breast cancer. Using questionnaire information from women and their mothers, we selected 100 women whose mothers reported taking DES while pregnant and 100 control women whose mothers had not taken DES. DNA methylation in blood was measured at 485,577 CpG sites using the Illumina HumanMethylation450 BeadChip. Associations between CpG methylation and DES exposure status were analyzed using robust linear regression with adjustment for blood cell composition and multiple comparisons. Although four CpGs had p<105, after accounting for multiple comparisons using the false discovery rate (FDR), none reached genome-wide significance. In conclusion, adult women exposed to DES in utero had no evidence of large persistent changes in blood DNA methylation.

  • 42.
    Harlid, Sophia
    et al.
    Epigenetics and Stem Cell Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina, USA.
    Xu, Zongli
    Panduri, Vijayalakshmi
    Sandler, Dale P
    Taylor, Jack A
    CpG sites associated with cigarette smoking: analysis of epigenome-wide data from the Sister Study.2014Ingår i: Journal of Environmental Health Perspectives, ISSN 0091-6765, E-ISSN 1552-9924, Vol. 122, nr 7, s. 673-8Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Smoking increases the risk of many diseases, and it is also linked to blood DNA methylation changes that may be important in disease etiology.

    OBJECTIVES: We sought to identify novel CpG sites associated with cigarette smoking.

    METHODS: We used two epigenome-wide data sets from the Sister Study to identify and confirm CpG sites associated with smoking. One included 908 women with methylation measurements at 27,578 CpG sites using the HumanMethylation27 BeadChip; the other included 200 women with methylation measurements for 473,844 CpG sites using the HumanMethylation450 BeadChip. Significant CpGs from the second data set that were not included in the 27K assay were validated by pyrosequencing in a subset of 476 samples from the first data set.

    RESULTS: Our study successfully confirmed smoking associations for 9 previously established CpGs and identified 2 potentially novel CpGs: cg26764244 in GNG12 (p = 9.0 × 10-10) and cg22335340 in PTPN6 (p = 2.9 × 10-05). We also found strong evidence of an association between smoking status and cg02657160 in CPOX (p = 7.3 × 10-7), which has not been previously reported. All 12 CpGs were undermethylated in current smokers and showed an increasing percentage of methylation in former and never-smokers.

    CONCLUSIONS: We identified 2 potentially novel smoking related CpG sites, and provided independent replication of 10 previously reported CpGs sites related to smoking, one of which is situated in the gene CPOX. The corresponding enzyme is involved in heme biosynthesis, and smoking is known to increase heme production. Our study extends the evidence base for smoking-related changes in DNA methylation.

  • 43. Hidaka, Akihisa
    et al.
    Harrison, Tabitha A.
    Cao, Yin
    Sakoda, Lori C.
    Barfield, Richard
    Giannakis, Marios
    Song, Mingyang
    Phipps, Amanda, I
    Figueiredo, Jane C.
    Zaidi, Syed H.
    Toland, Amanda E.
    Amitay, Efrat L.
    Berndt, Sonja, I
    Borozan, Ivan
    Chan, Andrew T.
    Gallinger, Steven
    Gunter, Marc J.
    Guinter, Mark A.
    Harlid, Sophia
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Hampel, Heather
    Jenkins, Mark A.
    Lin, Yi
    Moreno, Victor
    Newcomb, Polly A.
    Nishihara, Reiko
    Ogino, Shuji
    Obon-Santacana, Mireia
    Parfrey, Patrick S.
    Potter, John D.
    Slattery, Martha L.
    Steinfelder, Robert S.
    Um, Caroline Y.
    Wang, Xiaoliang
    Woods, Michael O.
    van Guelpen, Bethany
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi. Umeå universitet, Medicinska fakulteten, Wallenberg centrum för molekylär medicin vid Umeå universitet (WCMM).
    Thibodeau, Stephen N.
    Hoffmeister, Michael
    Sun, Wei
    Hsu, Li
    Buchanan, Daniel D.
    Campbell, Peter T.
    Peters, Ulrike
    Intake of Dietary Fruit, Vegetables, and Fiber and Risk of Colorectal Cancer According to Molecular Subtypes: A Pooled Analysis of 9 Studies2020Ingår i: Cancer Research, ISSN 0008-5472, E-ISSN 1538-7445, Vol. 80, nr 20, s. 4578-4590Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Protective associations of fruits, vegetables, and fiber intake with colorectal cancer risk have been shown in many, but not all epidemiologic studies. One possible reason for study heterogeneity is that dietary factors may have distinct effects by colorectal cancer molecular subtypes. Here, we investigate the association of fruit, vegetables, and fiber intake with four well-established colorectal cancer molecular subtypes separately and in combination. Nine observational studies including 9,592 cases with molecular subtypes for microsatellite instability (MSI), CpG island methylator phenotype (CIMP), and somatic mutations in BRAF and KRAS genes, and 7,869 controls were analyzed. Both case-only logistic regression analyses and polytomous logistic regression analyses (with one control set and multiple case groups) were used. Higher fruit intake was associated with a trend toward decreased risk of BRAF-mutated tumors [OR 4th vs. 1st quartile = 0.82 (95% confidence interval, 0.65–1.04)] but not BRAF-wildtype tumors [1.09 (0.97–1.22); P difference as shown in case-only analysis = 0.02]. This difference was observed in case–control studies and not in cohort studies. Compared with controls, higher fiber intake showed negative association with colorectal cancer risk for cases with microsatellite stable/MSI-low, CIMP-negative, BRAF-wildtype, and KRAS-wildtype tumors (Ptrend range from 0.03 to 3.4e-03), which is consistent with the traditional adenoma-colorectal cancer pathway. These negative associations were stronger compared with MSI-high, CIMP-positive, BRAF-mutated, or KRAS-mutated tumors, but the differences were not statistically significant. These inverse associations for fruit and fiber intake may explain, in part, inconsistent findings between fruit or fiber intake and colorectal cancer risk that have previously been reported.

  • 44. Huyghe, Jeroen R.
    et al.
    Bien, Stephanie A.
    Harrison, Tabitha A.
    Kang, Hyun Min
    Chen, Sai
    Schmit, Stephanie L.
    Conti, David V.
    Qu, Conghui
    Jeon, Jihyoun
    Edlund, Christopher K.
    Greenside, Peyton
    Wainberg, Michael
    Schumacher, Fredrick R.
    Smith, Joshua D.
    Levine, David M.
    Nelson, Sarah C.
    Sinnott-Armstrong, Nasa A.
    Albanes, Demetrius
    Alonso, M. Henar
    Anderson, Kristin
    Arnau-Collell, Coral
    Arndt, Volker
    Bamia, Christina
    Banbury, Barbara L.
    Baron, John A.
    Berndt, Sonja I.
    Bezieau, Stephane
    Bishop, D. Timothy
    Boehm, Juergen
    Boeing, Heiner
    Brenner, Hermann
    Brezina, Stefanie
    Buch, Stephan
    Buchanan, Daniel D.
    Burnett-Hartman, Andrea
    Butterbach, Katja
    Caan, Bette J.
    Campbell, Peter T.
    Carlson, Christopher S.
    Castellvi-Bel, Sergi
    Chan, Andrew T.
    Chang-Claude, Jenny
    Chanock, Stephen J.
    Chirlaque, Maria-Dolores
    Cho, Sang Hee
    Connolly, Charles M.
    Cross, Amanda J.
    Cuk, Katarina
    Curtis, Keith R.
    de la Chapelle, Albert
    Doheny, Kimberly F.
    Duggan, David
    Easton, Douglas F.
    Elias, Sjoerd G.
    Elliott, Faye
    English, Dallas R.
    Feskens, Edith J. M.
    Figueiredo, Jane C.
    Fischer, Rocky
    FitzGerald, Liesel M.
    Forman, David
    Gala, Manish
    Gallinger, Steven
    Gauderman, W. James
    Giles, Graham G.
    Gillanders, Elizabeth
    Gong, Jian
    Goodman, Phyllis J.
    Grady, William M.
    Grove, John S.
    Gsur, Andrea
    Gunter, Marc J.
    Haile, Robert W.
    Hampe, Jochen
    Hampel, Heather
    Harlid, Sophia
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Hayes, Richard B.
    Hofer, Philipp
    Hoffmeister, Michael
    Hopper, John L.
    Hsu, Wan-Ling
    Huang, Wen-Yi
    Hudson, Thomas J.
    Hunter, David J.
    Ibanez-Sanz, Gemma
    Idos, Gregory E.
    Ingersoll, Roxann
    Jackson, Rebecca D.
    Jacobs, Eric J.
    Jenkins, Mark A.
    Joshi, Amit D.
    Joshu, Corinne E.
    Keku, Temitope O.
    Key, Timothy J.
    Kim, Hyeong Rok
    Kobayashi, Emiko
    Kolonel, Laurence N.
    Kooperberg, Charles
    Kuehn, Tilman
    Kury, Sebastien
    Kweon, Sun-Seog
    Larsson, Susanna C.
    Laurie, Cecelia A.
    Le Marchand, Loic
    Leal, Suzanne M.
    Lee, Soo Chin
    Lejbkowicz, Flavio
    Lemire, Mathieu
    Li, Christopher I.
    Li, Li
    Lieb, Wolfgang
    Lin, Yi
    Lindblom, Annika
    Lindor, Noralane M.
    Ling, Hua
    Louie, Tin L.
    Mannisto, Satu
    Markowitz, Sanford D.
    Martin, Vicente
    Masala, Giovanna
    McNeil, Caroline E.
    Melas, Marilena
    Milne, Roger L.
    Moreno, Lorena
    Murphy, Neil
    Myte, Robin
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Naccarati, Alessio
    Newcomb, Polly A.
    Offit, Kenneth
    Ogino, Shuji
    Onland-Moret, N. Charlotte
    Pardini, Barbara
    Parfrey, Patrick S.
    Pearlman, Rachel
    Perduca, Vittorio
    Pharoah, Paul D. P.
    Pinchev, Mila
    Platz, Elizabeth A.
    Prentice, Ross L.
    Pugh, Elizabeth
    Raskin, Leon
    Rennert, Gad
    Rennert, Hedy S.
    Riboli, Elio
    Rodriguez-Barranco, Miguel
    Romm, Jane
    Sakoda, Lori C.
    Schafmayer, Clemens
    Schoen, Robert E.
    Seminara, Daniela
    Shah, Mitul
    Shelford, Tameka
    Shin, Min-Ho
    Shulman, Katerina
    Sieri, Sabina
    Slattery, Martha L.
    Southey, Melissa C.
    Stadler, Zsofia K.
    Stegmaier, Christa
    Su, Yu-Ru
    Tangen, Catherine M.
    Thibodeau, Stephen N.
    Thomas, Duncan C.
    Thomas, Sushma S.
    Toland, Amanda E.
    Trichopoulou, Antonia
    Ulrich, Cornelia M.
    Van den Berg, David J.
    van Duijnhoven, Franzel J. B.
    van Guelpen, Bethany
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    van Kranen, Henk
    Vijai, Joseph
    Visvanathan, Kala
    Vodicka, Pavel
    Vodickova, Ludmila
    Vymetalkova, Veronika
    Weigl, Korbinian
    Weinstein, Stephanie J.
    White, Emily
    Win, Aung Ko
    Wolf, C. Roland
    Wolk, Alicja
    Woods, Michael O.
    Wu, Anna H.
    Zaidi, Syed H.
    Zanke, Brent W.
    Zhang, Qing
    Zheng, Wei
    Scacheri, Peter C.
    Potter, John D.
    Bassik, Michael C.
    Kundaje, Anshul
    Casey, Graham
    Moreno, Victor
    Abecasis, Goncalo R.
    Nickerson, Deborah A.
    Gruber, Stephen B.
    Hsu, Li
    Peters, Ulrike
    Discovery of common and rare genetic risk variants for colorectal cancer2019Ingår i: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 51, nr 1, s. 76-+Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    To further dissect the genetic architecture of colorectal cancer (CRC), we performed whole-genome sequencing of 1,439 cases and 720 controls, imputed discovered sequence variants and Haplotype Reference Consortium panel variants into genome-wide association study data, and tested for association in 34,869 cases and 29,051 controls. Findings were followed up in an additional 23,262 cases and 38,296 controls. We discovered a strongly protective 0.3% frequency variant signal at CHD1. In a combined meta-analysis of 125,478 individuals, we identified 40 new independent signals at P < 5 x 10(-8), bringing the number of known independent signals for CRC to similar to 100. New signals implicate lower-frequency variants, Kruppel-like factors, Hedgehog signaling, Hippo-YAP signaling, long noncoding RNAs and somatic drivers, and support a role for immune function. Heritability analyses suggest that CRC risk is highly polygenic, and larger, more comprehensive studies enabling rare variant analysis will improve understanding of biology underlying this risk and influence personalized screening strategies and drug development.

  • 45.
    Huyghe, Jeroen R
    et al.
    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.
    Bien, Stephanie A
    Public Health Sciences Division, Fred Hutchinson Cancer Research Center, WA, Seattle, United States.
    Hampel, Heather
    Division of Human Genetics, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center, OH, Columbus, United States.
    Figueiredo, Jane C
    Department of Preventive Medicine, Keck School of Medicine of the 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.
    Schmit, Stephanie L
    Genomic Medicine Institute, Cleveland Clinic, OH, Cleveland, United States.
    Conti, David V
    Department of Preventive Medicine and Usc Norris Comprehensive Cancer Center, Keck School of Medicine of the University of Southern California, CA, Los Angeles, United States.
    Chen, Sai
    Department of Biostatistics and Center for Statistical Genetics, University of Michigan, MI, Ann Arbor, United States.
    Qu, Conghui
    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.
    Barfield, Richard
    Public Health Sciences Division, Fred Hutchinson Cancer Research Center, WA, Seattle, United States.
    Baron, John A
    Department of Medicine, University of North Carolina School of Medicine, NC, Chapel Hill, United States.
    Cross, Amanda J
    Department of Epidemiology and Biostatistics, Imperial College London, London, United Kingdom.
    Diergaarde, Brenda
    Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, PA, Pittsburgh, United States; Upmc Hillman Cancer Center, PA, Pittsburgh, United States.
    Duggan, David
    Translational Genomics Research Institute-An Affiliate of City of Hope, AZ, Phoenix, United States.
    Harlid, Sophia
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Imaz, Liher
    Public Health Division of Gipuzkoa, Health Department of Basque Country, San Sebastian, Spain.
    Kang, Hyun Min
    Department of Biostatistics and Center for Statistical Genetics, University of Michigan, MI, Ann Arbor, United States.
    Levine, David M
    Department of Biostatistics, University of Washington, WA, Seattle, United States.
    Perduca, Vittorio
    Laboratoire de Mathématiques Appliqueés MAP5 (UMR Cnrs 8145), Université Paris Descartes, Paris, France; Centre for Research in Epidemiology and Population Health (CESP), Institut Pour la Santé et la Recherche Médicale (INSERM) U1018, Université Paris-Saclay, Villejuif, France.
    Perez-Cornago, Aurora
    Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.
    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.
    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 Health, UT, Salt Lake City, United States.
    Toland, Amanda E
    Departments of Cancer Biology and Genetics and Internal Medicine, The Ohio State University, OH, Columbus, United States.
    Van Duijnhoven, Fränzel 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.
    Agudo, Antonio
    Unit of Nutrition and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology-IDIBELL, l'Hospitalet de Llobregat, Barcelona, Spain.
    Albanes, Demetrius
    Division of Cancer Epidemiology and Genetics, National Cancer Institute, MD, Bethesda, United States.
    Alonso, M Henar
    Cancer Prevention and Control Program, Catalan Institute of Oncology, IDIBELL, l'Hospitalet de Llobregat, Barcelona, Spain; Ciber Epidemiologiá y Salud Pública (CIBERESP), Madrid, Spain; Department of Clinical Sciences, Faculty of Medicine, University of Barcelona, Barcelona, Spain.
    Anderson, Kristin
    Division of Epidemiology and Community Health, University of Minnesota, MN, Minneapolis, United States.
    Arnau-Collell, Coral
    Gastroenterology Department, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigacion Biomedica en Red de Enfermedades Hepaticas y Digestivas (CIBEREHD), University of Barcelona, Barcelona, Spain.
    Arndt, Volker
    Division of Clinical Epidemiology and Aging Research, German Cancer Research Centre (DKFZ), Heidelberg, Germany.
    Banbury, Barbara L
    Public Health Sciences Division, Fred Hutchinson Cancer Research Center, WA, Seattle, United States.
    Bassik, Michael C
    Department of Genetics, Stanford University, California, Stanford, United States.
    Berndt, Sonja I
    Division of Cancer Epidemiology and Genetics, National Cancer Institute, MD, Bethesda, United States.
    Bézieau, Stéphane
    Service de Génétique Médicale, Centre Hospitalier Universitaire (CHU) de Nantes, Nantes, France.
    Bishop, D Timothy
    Leeds Institute of Medical Research at St James's, University of Leeds, Leeds, United Kingdom.
    Boehm, Juergen
    Huntsman Cancer Institute and Department of Population Health Sciences, University of Utah Health, Utah, Salt Lake City, United States.
    Boeing, Heiner
    Department of Epidemiology, German Institute of Human Nutrition (DIfE), Potsdam-Rehbrücke, Germany.
    Boutron-Ruault, Marie-Christine
    Centre for Research in Epidemiology and Population Health (CESP), Institut Pour la Santé et la Recherche Médicale (INSERM) U1018, Université Paris-Saclay, Villejuif, France; Institut Gustave Roussy, Université Paris-Saclay, Villejuif, France.
    Brenner, Hermann
    Division of Clinical Epidemiology and Aging Research, German Cancer Research Centre (DKFZ), Heidelberg, Germany; Division of Preventive Oncology, German Cancer Research Centre (DKFZ), National Center for Tumor Diseases (NCT), Heidelberg, Germany; German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.
    Brezina, Stefanie
    Institute of Cancer Research, Department of Medicine i, Medical University of Vienna, Vienna, Austria.
    Buch, Stephan
    Department of Medicine i, University Hospital Dresden, Technische Universität Dresden (TU Dresden), Dresden, Germany.
    Buchanan, Daniel D
    Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, VIC, Melbourne, Australia; Colorectal Oncogenomics Group, Genetic Epidemiology Laboratory, Department of Clinical Pathology, the University of Melbourne, VIC, Melbourne, Australia; Genomic Medicine and Family Cancer Clinic, Royal Melbourne Hospital, VIC, Melbourne, Australia.
    Burnett-Hartman, Andrea
    Institute for Health Research, Kaiser Permanente Colorado, CO, Denver, United States.
    Caan, Bette J
    Division of Research, Kaiser Permanente Medical Care Program, CA, Oakland, United States.
    Campbell, Peter T
    Behavioral and Epidemiology Research Group, American Cancer Society, GA, Atlanta, United States.
    Carr, Prudence R
    Division of Clinical Epidemiology, German Cancer Research Centre (DKFZ), Heidelberg, Germany.
    Castells, Antoni
    Gastroenterology Department, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigacion Biomedica en Red de Enfermedades Hepaticas y Digestivas (CIBEREHD), University of Barcelona, Barcelona, Spain.
    Castellví-Bel, Sergi
    Gastroenterology Department, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigacion Biomedica en Red de Enfermedades Hepaticas y Digestivas (CIBEREHD), 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; 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 Centre (DKFZ), Heidelberg, Germany; Cancer Epidemiology Group, University Medical Centre Hamburg-Eppendorf, University Cancer Centre Hamburg (UCCH), Hamburg, Germany.
    Chanock, Stephen J
    Division of Cancer Epidemiology and Genetics, National Cancer Institute, MD, Bethesda, United States.
    Curtis, Keith R
    Public Health Sciences Division, Fred Hutchinson Cancer Research Center, WA, Seattle, United States.
    De La Chapelle, Albert
    Department of Cancer Biology and Genetics and the Comprehensive Cancer Center, The Ohio State University, OH, Columbus, United States.
    Easton, Douglas F
    Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom.
    English, Dallas R
    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.
    Feskens, Edith J M
    Division of Human Nutrition and Health, Wageningen University and Research, Wageningen, Netherlands.
    Gala, Manish
    Division of Gastroenterology, Massachusetts General 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.
    Gallinger, Steven J
    Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, ON, Toronto, Canada.
    Gauderman, W James
    Department of Preventive Medicine and Usc Norris Comprehensive Cancer Center, Keck School of Medicine of the University of Southern California, CA, Los Angeles, United States.
    Giles, Graham G
    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.
    Goodman, Phyllis J
    Swog Statistical Center, Fred Hutchinson Cancer Research Center, WA, Seattle, United States.
    Grady, William M
    Clinical Research Division, Fred Hutchinson Cancer Research Center, WA, Seattle, United States; Department of Medicine, University of Washington School of Medicine, WA, Seattle, United States.
    Grove, John S
    University of Hawai'i Cancer Center, HI, Honolulu, United States.
    Gsur, Andrea
    Institute of Cancer Research, Department of Medicine i, Medical University of Vienna, Vienna, Austria.
    Gunter, Marc J
    Nutrition and Metabolism Section, International Agency for Research on Cancer, World Health Organization, Lyon, France.
    Haile, Robert W
    Department of Medicine, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, CA, Los Angeles, United States.
    Hampe, Jochen
    Department of Medicine i, University Hospital Dresden, Technische Universität Dresden (TU Dresden), Dresden, Germany.
    Hoffmeister, Michael
    Division of Clinical Epidemiology and Aging Research, German Cancer Research Centre (DKFZ), Heidelberg, Germany.
    Hopper, John L
    Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The 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.
    Hsu, Wan-Ling
    Department of Biostatistics, University of Washington, WA, Seattle, United States.
    Huang, Wen-Yi
    Division of Cancer Epidemiology and Genetics, National Cancer Institute, MD, Bethesda, United States.
    Hudson, Thomas J
    Ontario Institute for Cancer Research, ON, Toronto, Canada.
    Jenab, Mazda
    Nutrition and Metabolism Section, International Agency for Research on Cancer, World Health Organization, Lyon, France.
    Jenkins, Mark A
    Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, VIC, Melbourne, Australia.
    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.
    Keku, Temitope O
    Center for Gastrointestinal Biology and Disease, University of North Carolina, NC, Chapel Hill, United States.
    Kooperberg, Charles
    Public Health Sciences Division, Fred Hutchinson Cancer Research Center, WA, Seattle, United States.
    Kühn, Tilman
    Division of Cancer Epidemiology, German Cancer Research Centre (DKFZ), Heidelberg, Germany.
    Küry, Sébastien
    Service de Génétique Médicale, Centre Hospitalier Universitaire (CHU) de Nantes, Nantes, France.
    Le Marchand, Loic
    University of Hawai'i Cancer Center, HI, Honolulu, United States.
    Lejbkowicz, Flavio
    The Clalit Health Services, Personalized Genomic Service, Carmel Medical Center, Haifa, Israel; Department of Community Medicine and Epidemiology, Lady Davis Carmel Medical Center, Haifa, Israel; Clalit National Cancer Control Center, Haifa, Israel.
    Li, Christopher I
    Public Health Sciences Division, Fred Hutchinson Cancer Research Center, WA, Seattle, United States.
    Li, Li
    Department of Family Medicine, University of Virginia, VA, Charlottesville, United States.
    Lieb, Wolfgang
    Institute of Epidemiology, PopGen Biobank, Christian-Albrechts-University Kiel, Kiel, Germany.
    Lindblom, Annika
    Department of Clinical Genetics, Karolinska University Hospital, Stockholm, Sweden; Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
    Lindor, Noralane M
    Department of Health Science Research, Mayo Clinic, AZ, Scottsdale, United States.
    Männistö, Satu
    Department of Public Health Solutions, National Institute for Health and Welfare, Helsinki, Finland.
    Markowitz, Sanford D
    Departments of Medicine and Genetics, Case Comprehensive Cancer Center, Case Western Reserve University, University Hospitals of Cleveland, OH, Cleveland, United States.
    Milne, Roger L
    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.
    Moreno, Lorena
    Gastroenterology Department, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigacion Biomedica en Red de Enfermedades Hepaticas y Digestivas (CIBEREHD), University of Barcelona, Barcelona, Spain.
    Murphy, Neil
    Nutrition and Metabolism Section, International Agency for Research on Cancer, World Health Organization, Lyon, France.
    Nassir, Rami
    Department of Pathology, School of Medicine, Umm Al-Qura'a University, Mecca, Saudi Arabia.
    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.
    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; Department of Oncologic Pathology, Dana-Farber Cancer Institute, MA, Boston, United States; Program in Mpe Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, MA, Boston, United States.
    Panico, Salvatore
    Dipartimento di Medicina Clinica e Chirurgia, University of Naples Federico II, Naples, Italy.
    Parfrey, Patrick S
    Clinical Epidemiology Unit, Faculty of Medicine, Memorial University of Newfoundland, Newfoundland, St. John's, Canada.
    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.
    Phipps, Amanda I
    Public Health Sciences Division, Fred Hutchinson Cancer Research Center, WA, Seattle, United States; Department of Epidemiology, University of Washington, WA, Seattle, United States.
    Platz, Elizabeth A
    Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Johns Hopkins University, MD, Baltimore, United States.
    Potter, John D
    Public Health Sciences Division, Fred Hutchinson Cancer Research Center, WA, Seattle, United States.
    Prentice, Ross L
    Public Health Sciences Division, Fred Hutchinson Cancer Research Center, WA, Seattle, United States.
    Qi, Lihong
    Department of Public Health Sciences, School of Medicine, University of California Davis, CA, Davis, United States.
    Raskin, Leon
    Division of Epidemiology, Vanderbilt Epidemiology Center, Vanderbilt University School of Medicine, TN, Nashville, United States.
    Rennert, Gad
    Department of Community Medicine and Epidemiology, Lady Davis Carmel Medical Center, Haifa, Israel; Clalit National Cancer Control Center, Haifa, Israel; Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
    Rennert, Hedy S
    Department of Community Medicine and Epidemiology, Lady Davis Carmel Medical Center, Haifa, Israel; Clalit National Cancer Control Center, Haifa, Israel; Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
    Riboli, Elio
    School of Public Health, Imperial College London, London, United Kingdom.
    Schafmayer, Clemens
    Department of General Surgery, University Hospital Rostock, Rostock, Germany.
    Schoen, Robert E
    Department of Medicine and Epidemiology, University of Pittsburgh Medical Center, PA, Pittsburgh, United States.
    Seminara, Daniela
    Division of Cancer Control and Population Sciences, National Cancer Institute, MD, Bethesda, United States.
    Song, Mingyang
    Division of Gastroenterology, Massachusetts General 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; Department of Nutrition, Harvard T.H. Chan School of Public Health, Harvard University, MA, Boston, 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, MayoClinic, MN, Rochester, United States.
    Thomas, Duncan C
    Department of Preventive Medicine and Usc Norris Comprehensive Cancer Center, Keck School of Medicine of the University of Southern California, CA, Los Angeles, United States.
    Trichopoulou, Antonia
    Hellenic Health Foundation, Athens, Greece; Who Collaborating Center for Nutrition and Health, Unit of Nutritional Epidemiology and Nutrition in Public Health, Department of Hygiene, Epidemiology and Medical Statistics, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.
    Ulrich, Cornelia M
    Huntsman Cancer Institute and Department of Population Health Sciences, University of Utah Health, Utah, Salt Lake City, United States.
    Visvanathan, Kala
    Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Johns Hopkins University, 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; 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.
    Weigl, Korbinian
    Division of Clinical Epidemiology and Aging Research, German Cancer Research Centre (DKFZ), Heidelberg, Germany; German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany; Medical Faculty, University of Heidelberg, Heidelberg, Germany.
    Weinstein, Stephanie J
    Division of Cancer Epidemiology and Genetics, National Cancer Institute, MD, Bethesda, United States.
    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
    Discipline of Genetics, Memorial University of Newfoundland, Newfoundland, St. John's, Canada.
    Wu, Anna H
    Department of Preventive Medicine and Usc Norris Comprehensive Cancer Center, Keck School of Medicine of the University of Southern California, CA, Los Angeles, United States.
    Abecasis, Goncalo R
    Department of Biostatistics and Center for Statistical Genetics, University of Michigan, MI, Ann Arbor, United States.
    Nickerson, Deborah A
    Department of Genome Sciences, University of Washington, WA, Seattle, United States.
    Scacheri, Peter C
    Department of Genetics and Genome Sciences, Case Western Reserve University School of Medicine, Case Comprehensive Cancer Center, OH, Cleveland, United States.
    Kundaje, Anshul
    Department of Genetics, Stanford University, California, Stanford, United States; Department of Computer Science, Stanford University, CA, Stanford, United States.
    Casey, Graham
    Center for Public Health Genomics, University of Virginia, VA, Charlottesville, United States.
    Gruber, Stephen B
    Department of Preventive Medicine, Usc Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine, CA, Los Angeles, United States; City of Hope National Medical Center, CA, Duarte, 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.
    Moreno, Victor
    Cancer Prevention and Control Program, Catalan Institute of Oncology, IDIBELL, l'Hospitalet de Llobregat, Barcelona, Spain; Ciber Epidemiologiá y Salud Pública (CIBERESP), Madrid, Spain; Department of Clinical Sciences, Faculty of Medicine, University of Barcelona, Barcelona, Spain.
    Hayes, Richard B
    Division of Epidemiology, Department of Population Health, New York University School of Medicine, NY, New York, United States.
    Newcomb, Polly A
    Public Health Sciences Division, Fred Hutchinson Cancer Research Center, WA, Seattle, United States; Department of Epidemiology, University of Washington, WA, Seattle, United States.
    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.
    Genetic architectures of proximal and distal colorectal cancer are partly distinct2021Ingår i: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 70, nr 7, s. 1325-1334Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: An understanding of the etiologic heterogeneity of colorectal cancer (CRC) is critical for improving precision prevention, including individualized screening recommendations and the discovery of novel drug targets and repurposable drug candidates for chemoprevention. Known differences in molecular characteristics and environmental risk factors among tumors arising in different locations of the colorectum suggest partly distinct mechanisms of carcinogenesis. The extent to which the contribution of inherited genetic risk factors for CRC differs by anatomical subsite of the primary tumor has not been examined.

    Design: To identify new anatomical subsite-specific risk loci, we performed genome-wide association study (GWAS) meta-analyses including data of 48 214 CRC cases and 64 159 controls of European ancestry. We characterised effect heterogeneity at CRC risk loci using multinomial modelling.

    Results: We identified 13 loci that reached genome-wide significance (p<5×10-8) and that were not reported by previous GWASs for overall CRC risk. Multiple lines of evidence support candidate genes at several of these loci. We detected substantial heterogeneity between anatomical subsites. Just over half (61) of 109 known and new risk variants showed no evidence for heterogeneity. In contrast, 22 variants showed association with distal CRC (including rectal cancer), but no evidence for association or an attenuated association with proximal CRC. For two loci, there was strong evidence for effects confined to proximal colon cancer.

    Conclusion: Genetic architectures of proximal and distal CRC are partly distinct. Studies of risk factors and mechanisms of carcinogenesis, and precision prevention strategies should take into consideration the anatomical subsite of the tumour.

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  • 46.
    Iguacel, Isabel
    et al.
    International Agency for Research on Cancer, Nutrition and Metabolism Section, Lyon CEDEX 08, France; Department of Physiatry and Nursing, Faculty of Health Sciences, University of Zaragoza, Zaragoza, Spain; Instituto Agroalimentario de Aragón, Zaragoza, Spain; Instituto de Investigación Sanitaria Aragón, Zaragoza, Spain; Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición, Zaragoza, Spain.
    Schmidt, Julie A.
    Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.
    Perez-Cornago, Aurora
    Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.
    Van Puyvelde, Heleen
    International Agency for Research on Cancer, Nutrition and Metabolism Section, Lyon CEDEX 08, France; Department of Public Health and Primary Care, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium.
    Travis, Ruth
    Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.
    Stepien, Magdalena
    International Agency for Research on Cancer, Nutrition and Metabolism Section, Lyon CEDEX 08, France.
    Scalbert, Augustin
    International Agency for Research on Cancer, Nutrition and Metabolism Section, Lyon CEDEX 08, France.
    Casagrande, Corinne
    International Agency for Research on Cancer, Nutrition and Metabolism Section, Lyon CEDEX 08, France.
    Weiderpass, Elisabete
    International Agency for Research on Cancer, Nutrition and Metabolism Section, Lyon CEDEX 08, France.
    Riboli, Elio
    Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom.
    Schulze, Matthias B.
    Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany; Institute of Nutritional Sciences, University of Potsdam, Nuthetal, Germany.
    Skeie, Guri
    Department of Community Medicine, Faculty of Health Sciences, UiT-The Arctic University of Norway, Tromsø, Norway.
    Bodén, Stina
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Boeing, Heiner
    Department of Epidemiology, German Institute for Human Nutrition Potsdam-Rehbrücke, Nuthetal, Germany.
    Cross, Amanda J.
    Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom.
    Harlid, Sophia
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Jensen, Torill Enget
    Department of Community Medicine, Faculty of Health Sciences, UiT-The Arctic University of Norway, Tromsø, Norway.
    Huerta, José M.
    Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca, Murcia, Spain; CIBER Epidemiología y Salud Pública (CIBERESP), Spain.
    Katzke, Verena
    Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
    Kühn, Tilman
    Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
    Lujan-Barroso, Leila
    Unit of Nutrition and Cancer, Catalan Institute of Oncology - ICO, Nutrition and Cancer Group, Bellvitge Biomedical Research Institute -IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain.
    Masala, Giovanna
    Cancer Risk Factors and Life-Style Epidemiology Unit, Institute for Cancer Research, Prevention and Clinical Network - ISPRO, Florence, Italy.
    Rodriguez-Barranco, Miguel
    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.
    Rostgaard-Hansen, Agnetha Linn
    Department of Public Health, Danish Cancer Society Research Center Diet, Genes and Environment, University of Copenhagen, Copenhagen, Denmark.
    van der Schouw, Yvonne T.
    Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands.
    Vermeulen, Roel
    Department of Public Health and Primary Care, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium; Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands.
    Tagliabue, Giovanna
    Lombardy Cancer Registry Unit Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milano, Italy.
    Tjønneland, Anne
    Department of Public Health, Danish Cancer Society Research Center Diet, Genes and Environment, University of Copenhagen, Copenhagen, Denmark.
    Trevisan, Morena
    Unit of Cancer Epidemiology– CeRMS, Department of Medical Sciences, University of Turin, Turin, Italy.
    Ferrari, Pietro
    International Agency for Research on Cancer, Nutrition and Metabolism Section, Lyon CEDEX 08, France.
    Gunter, Marc J.
    International Agency for Research on Cancer, Nutrition and Metabolism Section, Lyon CEDEX 08, France.
    Huybrechts, Inge
    International Agency for Research on Cancer, Nutrition and Metabolism Section, Lyon CEDEX 08, France.
    Associations between dietary amino acid intakes and blood concentration levels2021Ingår i: Clinical Nutrition, ISSN 0261-5614, E-ISSN 1532-1983, Vol. 40, nr 6, s. 3772-3779Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background and aims: Emerging evidence suggests a role of amino acids (AAs) in the development of various diseases including renal failure, liver cirrhosis, diabetes and cancer. However, mechanistic pathways and the effects of dietary AA intakes on circulating levels and disease outcomes are unclear. We aimed to compare protein and AA intakes, with their respective blood concentrations in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.

    Methods: Dietary protein and AA intakes were assessed via the EPIC dietary questionnaires (DQ) and 24-h dietary recalls (24-HDR). A subsample of 3768 EPIC participants who were free of cancer had blood AA concentrations measured. To investigate how circulating levels relate to their respective intakes, dietary AA intake was examined in quintiles and ANOVA tests were run. Pearson correlations were examined for continous associations between intakes and blood concentrations.

    Results: Dietary AA intakes (assessed with the DQ) and blood AA concentrations were not strongly correlated (−0.15 ≤ r ≤ 0.17) and the direction of the correlations depended on AA class: weak positive correlations were found for most essential AAs (isoleucine, leucine, lysine, methionine, threonine, tryptophan, and valine) and conditionally essential AAs (arginine and tyrosine), while negative associations were found for non-essential AAs. Similar results were found when using the 24-HDR. When conducting ANOVA tests for essential AAs, higher intake quintiles were linked to higher blood AA concentrations, except for histidine and phenylalanine. For non-essential AAs and glycine, an inverse relationship was observed. Conditionally-essential AAs showed mixed results.

    Conclusions: Weak positive correlations and dose responses were found between most essential and conditionally essential AA intakes, and blood concentrations, but not for the non-essential AAs. These results suggest that intake of dietary AA might be related to physiological AA status, particularly for the essential AAs. However, these results should be further evaluated and confirmed in large-scale prospective studies.

  • 47. Johansson, Stefan
    et al.
    Buchmayer, Susanne
    Harlid, Sophia
    Department of Medical Microbiology, Lund University, Malmö University Hospital, Sweden.
    Iliadou, Anastasia
    Sjöholm, Malin
    Grillner, Lena
    Norman, Mikael
    Sparén, Per
    Dillner, Joakim
    Cnattingius, Sven
    Infection with Parvovirus B19 and Herpes viruses in early pregnancy and risk of second trimester miscarriage or very preterm birth2008Ingår i: Reproductive Toxicology, ISSN 0890-6238, E-ISSN 1873-1708, Vol. 26, nr 3-4, s. 298-302Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    We investigated whether infections with Parvovirus B19 and Herpes viruses in early pregnancy increase risks of second trimester miscarriage or delivery before 32 gestational weeks. Blood samples taken in early pregnancy were analyzed for Parvovirus B19 or Herpes viruses. Viremia was found in blood samples of 11 (4.7%) women with second trimester miscarriage and 10 (3.7%) women with very preterm birth, compared to 5 (1.7%) women who delivered at term, corresponding to adjusted odds ratios [95% CI] of 3.32 [0.93, 11.8] and 2.21 [0.71, 6.84], respectively. In stratified analyses, Parvovirus B19 viremia was associated with adjusted odds ratios of 3.76 [0.77, 18.3] for second trimester miscarriage and 2.66 [0.64, 11.1] for very preterm birth. Corresponding odds ratios for Human Herpes virus 6 viremia was 2.52 [0.33, 19.5] and 1.08 [0.14, 8.08], respectively. In conclusion, this study lends some support to the hypothesis that women with viremia in early pregnancy may face an increased risk of second trimester miscarriage or very preterm birth. Studies with larger sample sizes are needed.

  • 48.
    Jordahl, Kristina M.
    et al.
    Department of Epidemiology, School of Public Health, University of Washington, Seattle, Washington; Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
    Shcherbina, Anna
    Department of Genetics, Stanford University, Stanford, California; Department of Computer Science, Stanford University, Stanford, California.
    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).
    Peters, Ulrike
    Department of Epidemiology, School of Public Health, University of Washington, Seattle, Washington; Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
    Beyond GWAS of Colorectal Cancer: Putative Causal Variant for the 10q24.2 Region2022Ingår i: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 31, nr 5, s. 1077-1089Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Currently known associations between common genetic variants and colorectal cancer explain less than half of its heritability of 25%. As alcohol consumption has a J-shape association with colorectal cancer risk, nondrinking and heavy drinking are both risk factors for colorectal cancer.

    Methods: Individual-level data was pooled from the Colon Cancer Family Registry, Colorectal Transdisciplinary Study, and Genetics and Epidemiology of Colorectal Cancer Consortium to compare nondrinkers (≤1 g/day) and heavy drinkers (>28 g/day) with light-to-moderate drinkers (1-28 g/day) in GxE analyses. To improve power, we implemented joint 2df and 3df tests and a novel two-step method that modifies the weighted hypothesis testing framework. We prioritized putative causal variants by predicting allelic effects using support vector machine models.

    Results: For nondrinking as compared with light-to-moderate drinking, the hybrid two-step approach identified 13 significant SNPs with pairwise r2 > 0.9 in the 10q24.2/COX15 region. When stratified by alcohol intake, the A allele of lead SNP rs2300985 has a dose-response increase in risk of colorectal cancer as compared with the G allele in light-to-moderate drinkers [OR for GA genotype = 1.11; 95% confidence interval (CI), 1.06-1.17; OR for AA genotype = 1.22; 95% CI, 1.14-1.31], but not in nondrinkers or heavy drinkers. Among the correlated candidate SNPs in the 10q24.2/COX15 region, rs1318920 was predicted to disrupt an HNF4 transcription factor binding motif.

    Conclusions: Our study suggests that the association with colorectal cancer in 10q24.2/COX15 observed in genome-wide association study is strongest in nondrinkers. We also identified rs1318920 as the putative causal regulatory variant for the region.

    Impact: The study identifies multifaceted evidence of a possible functional effect for rs1318920.

  • 49.
    Lu, Sai San Moon
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi. Umeå universitet, Medicinska fakulteten, Institutionen för epidemiologi och global hälsa.
    Mohammed, Zahraa
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Häggström, Christel
    Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
    Myte, Robin
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Lindquist, Elisabeth
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
    Gylfe, Åsa
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi. Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR).
    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.
    Antibiotics Use and Subsequent Risk of Colorectal Cancer: A Swedish Nationwide Population-Based Study2022Ingår i: Journal of the National Cancer Institute, ISSN 0027-8874, E-ISSN 1460-2105, Vol. 114, nr 1, s. 38-46Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Antibiotics use may increase colorectal cancer (CRC) risk by altering the gut microbiota, with suggestive evidence reported. Our study aims to investigate antibiotics use in relation to subsequent CRC risk.

    METHODS: This is a nationwide, population-based study with a matched case-control design (first primary CRC cases and 5 matched, cancer-free controls). Complete-population data, extracted from Swedish national registers for the period 2005-2016, were used to calculate odds ratios and 95% confidence intervals.

    RESULTS: We included 40 545 CRC cases and 202 720 controls. Using the full dataset, we found a positive association between more frequent antibiotics use and CRC, excluding antibiotics prescribed within 2 years of diagnosis attenuated results toward the null. In site-specific analyses, excluding the 2-year washout, the positive association was confined to the proximal colon (adjusted odds ratio for very high use vs no use = 1.17, 95% confidence interval = 1.05 to 1.31). For rectal cancer, an inverse association, which appears to be driven by women, was observed. Quinolones and sulfonamides and/or trimethoprims were positively associated with proximal colon cancer, whereas a more general inverse association, across antibiotics classes, was observed for rectal cancer. We found no association between methenamine hippurate, a urinary tract antiseptic not affecting the gut microbiota, and CRC risk.

    CONCLUSIONS: This register-based study covering the entire population of Sweden found a robust association between antibiotics use and higher risk of proximal colon cancer and an inverse association with rectal cancer in women. This study strengthens the evidence from previous investigations and adds important insight into site-specific colorectal carcinogenesis.

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  • 50.
    Lu, Sai San Moon
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Rutegård, Martin
    Umeå universitet, Medicinska fakulteten, Wallenberg centrum för molekylär medicin vid Umeå universitet (WCMM). Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap.
    Ahmed, Maghfoor
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Häggström, Christel
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Gylfe, Åsa
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi. Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR). Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS).
    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.
    Prediagnostic prescription antibiotics use and survival in patients with colorectal cancer: a swedish national register-based study2023Ingår i: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 32, nr 10, s. 1391-1401Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Antibiotics use is associated with higher colorectal cancer risk, but little is known regarding any potential effects on survival.

    METHODS: We conducted a nationwide cohort study, using complete-population data from Swedish national registers between 2005 and 2020, to investigate prediagnostic prescription antibiotics use in relation to survival in colorectal cancer patients.

    RESULTS: We identified 36,061 stage I-III and 11,242 stage IV colorectal cancer cases diagnosed between 2010 and 2019. For stage I-III, any antibiotics use (binary yes/no variable) was not associated with overall or cancer-specific survival. Compared with no use, moderate antibiotics use (total 11-60 days) was associated with slightly better cancer-specific survival [adjusted HR (aHR) = 0.93; 95% confidence interval (CI), 0.86-0.99)], whereas very high use (>180 days) was associated with worse survival [overall survival (OS) aHR = 1.42; 95% CI, 1.26-1.60, cancer-specific survival aHR = 1.31; 95% CI, 1.10-1.55]. In analyses by different antibiotic types, although not statistically significant, worse survival outcomes were generally observed across several antibiotics, particularly macrolides and/or lincosamides. In stage IV colorectal cancer, inverse relationships between antibiotics use and survival were noted.

    CONCLUSIONS: Overall, our findings do not support any substantial detrimental effects of prediagnostic prescription antibiotics use on cancer-specific survival after colorectal cancer diagnosis, with the possible exception of very high use in stage I-III colorectal cancer. Further investigation is warranted to confirm and understand these results.

    IMPACT: Although the study findings require confirmation, physicians probably do not need to factor in prediagnostic prescription antibiotics use in prognosticating patients with colorectal cancer.

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