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  • 1.
    Aglago, Elom K.
    et al.
    Nutrition and Metabolism Branch, International Agency for Research on Cancer (IARC), World Health Organization, Lyon, France.
    Murphy, Neil
    Nutrition and Metabolism Branch, International Agency for Research on Cancer (IARC), World Health Organization, Lyon, France.
    Huybrechts, Inge
    Nutrition and Metabolism Branch, International Agency for Research on Cancer (IARC), World Health Organization, Lyon, France.
    Nicolas, Geneviève
    Nutrition and Metabolism Branch, International Agency for Research on Cancer (IARC), World Health Organization, Lyon, France.
    Casagrande, Corinne
    Nutrition and Metabolism Branch, International Agency for Research on Cancer (IARC), World Health Organization, Lyon, France.
    Fedirko, Veronika
    Department of Epidemiology, Rollins School of Public Health, Winship Cancer Institute, Emory University, GA, Atlanta, United States.
    Weiderpass, Elisabete
    Office of the Director, International Agency for Research on Cancer (IARC), World Health Organization, Lyon, France.
    Rothwell, Joseph A.
    CESP, Faculté de médecine—Université Paris-Saclay, UVSQ, INSERM, Villejuif, France; Gustave Roussy, Villejuif, France.
    Dahm, Christina C.
    Department of Public Health, Aarhus University, Aarhus, Denmark.
    Olsen, Anja
    Danish Cancer Society Research Center, Copenhagen, Denmark; Department of Public Health, University of Aarhus, Aarhus, Denmark.
    Tjønneland, Anne
    Danish Cancer Society Research Center, Copenhagen, Denmark; Department of Public Health, University of Copenhagen, Copenhagen, Denmark.
    Kaaks, Rudolf
    German Cancer Research Center (DKFZ), Foundation under Public Law, Heidelberg, Germany.
    Katzke, Verena
    German Cancer Research Center (DKFZ), Foundation under Public Law, 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, Nuthetal, Germany.
    Masala, Giovanna
    Cancer Risk Factors and Life-Style Epidemiology Unit, Institute for Cancer Research, Prevention and Clinical Network –ISPRO, Florence, Italy.
    Agnoli, Claudia
    Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy.
    Panico, Salvatore
    Dipartimento di Medicina Clinica e Chirurgia Federico II University, Naples, Italy.
    Tumino, Rosario
    Cancer Registry and Histopathology Department, Provincial Health Authority (ASP 7), Ragusa, Italy.
    Sacerdote, Carlotta
    Unit of Cancer Epidemiology, Città della Salute e della Scienza University-Hospital, Turin, Italy.
    Bueno-de-Mesquita, Bas H.
    Former senior scientist, Dept. for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment (RIVM), Bilthoven, Netherlands.
    Derksen, Jeroen W. G.
    Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands.
    Skeie, Guri
    Faculty of Health Sciences, Department of Community Medicine, University of Tromsø, The Arctic University of Norway, Tromsø, Norway.
    Gram, Inger Torhild
    Faculty of Health Sciences, Department of Community Medicine, University of Tromsø, The Arctic University of Norway, Tromsø, Norway.
    Brustad, Magritt
    Faculty of Health Sciences, Department of Community Medicine, University of Tromsø, The Arctic University of Norway, Tromsø, Norway.
    Jakszyn, Paula
    Unit of Nutrition and Cancer, Cancer Epidemiology Research Programme, Catalan Institute of Oncology (ICO-IDIBELL), Barcelona, Spain; Blanquerna School of Health Sciences, Ramon Llull University, Barcelona, Spain.
    Sánchez, Maria-Jose
    Escuela Andaluza de Salud Pública (EASP), Granada, Spain; Instituto de Investigación Biosanitaria ibs.GRANADA, Granada, Spain; Department of Preventive Medicine and Public Health, University of Granada, Granada, Spain; Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain.
    Amiano, Pilar
    Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain; Public Health Division of Gipuzkoa, BioDonostia Research Institute, Donostia-San Sebastian, Spain.
    Huerta, José María
    Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain; Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca, Murcia, Spain.
    Ericson, Ulrika
    Department of Clinical Sciences in Malmö, Lund University, Malmö, Sweden.
    Wennberg, Maria
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Sustainable Health.
    Perez-Cornago, Aurora
    Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.
    Heath, Alicia K.
    School of Public Health, Imperial College London, London, United Kingdom.
    Jenab, Mazda
    Nutrition and Metabolism Branch, International Agency for Research on Cancer (IARC), World Health Organization, Lyon, France.
    Chajes, Veronique
    Nutrition and Metabolism Branch, International Agency for Research on Cancer (IARC), World Health Organization, Lyon, France.
    Gunter, Marc J.
    Nutrition and Metabolism Branch, International Agency for Research on Cancer (IARC), World Health Organization, Lyon, France.
    Dietary intake and plasma phospholipid concentrations of saturated, monounsaturated and trans fatty acids and colorectal cancer risk in the European Prospective Investigation into Cancer and Nutrition cohort2021In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 149, no 4, p. 865-882Article in journal (Refereed)
    Abstract [en]

    Epidemiologic studies examining the association between specific fatty acids and colorectal cancer (CRC) risk are inconclusive. We investigated the association between dietary estimates and plasma levels of individual and total saturated (SFA), monounsaturated (MUFA), industrial-processed trans (iTFA), and ruminant-sourced trans (rTFA) fatty acids, and CRC risk in the European Prospective Investigation into Cancer and Nutrition (EPIC). Baseline fatty acid intakes were estimated in 450 112 participants (6162 developed CRC, median follow-up = 15 years). In a nested case-control study, plasma phospholipid fatty acids were determined by gas chromatography in 433 colon cancer cases and 433 matched controls. Multivariable-adjusted hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CIs) were computed using Cox and conditional logistic regression, respectively. Dietary total SFA (highest vs lowest quintile, HRQ5vsQ1 = 0.80; 95%CI:0.69-0.92), myristic acid (HRQ5vsQ1 = 0.83, 95%CI:0.74-0.93) and palmitic acid (HRQ5vsQ1 = 0.81, 95%CI:0.70-0.93) were inversely associated with CRC risk. Plasma myristic acid was also inversely associated with colon cancer risk (highest vs lowest quartile, ORQ4vsQ1 = 0.51; 95%CI:0.32-0.83), whereas a borderline positive association was found for plasma stearic acid (ORQ4vsQ1 = 1.63; 95%CI:1.00-2.64). Dietary total MUFA was inversely associated with colon cancer (per 1-SD increment, HR1-SD = 0.92, 95%CI: 0.85-0.98), but not rectal cancer (HR1-SD = 1.04, 95%CI:0.95-1.15, Pheterogeneity = 0.027). Dietary iTFA, and particularly elaidic acid, was positively associated with rectal cancer (HR1-SD = 1.07, 95%CI:1.02-1.13). Our results suggest that total and individual saturated fatty acids and fatty acids of industrial origin may be relevant to the aetiology of CRC. Both dietary and plasma myristic acid levels were inversely associated with colon cancer risk, which warrants further investigation.

  • 2. Aleksandrova, Krasimira
    et al.
    Drogan, Dagmar
    Boeing, Heiner
    Jenab, Mazda
    Bas Bueno-de-Mesquita, H
    Jansen, Eugene
    van Duijnhoven, Fränzel J B
    Rinaldi, Sabina
    Fedirko, Veronika
    Romieu, Isabelle
    Kaaks, Rudolf
    Riboli, Elio
    Gunter, Marc J
    Romaguera, Dora
    Westhpal, Sabine
    Overvad, Kim
    Tjønneland, Anne
    Halkjaer, Jytte
    Boutron-Ruault, Marie-Christine
    Clavel-Chapelon, Françoise
    Lukanova, Annekatrin
    Trichopoulou, Antonia
    Trichopoulos, Dimitrios
    Vidalis, Pavlos
    Panico, Salvatore
    Agnoli, Claudia
    Palli, Domenico
    Tumino, Rosario
    Vineis, Paolo
    Buckland, Genevieve
    Sánchez-Cruz, José-Juan
    Dorronsoro, Miren
    Díaz, María José Tormo
    Barricarte, Aurelio
    Ramon Quiros, J
    Peeters, Petra H
    May, Anne M
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Palmqvist, Richard
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Crowe, Francesca L
    Khaw, Kay-Tee
    Wareham, Nickolas
    Pischon, Tobias
    Adiposity, mediating biomarkers and risk of colon cancer in the European prospective investigation into cancer and nutrition study2014In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 134, no 3, p. 612-621Article in journal (Refereed)
    Abstract [en]

    Adiposity is a risk factor for colon cancer, but underlying mechanisms are not well understood. We evaluated the extent to which 11 biomarkers with inflammatory and metabolic actions mediate the association of adiposity measures, waist circumference (WC) and body mass index (BMI), with colon cancer in men and women. We analyzed data from a prospective nested case-control study among 662 incident colon cancer cases matched within risk sets to 662 controls. Relative risks (RRs) and 95% confidence intervals (CIs) were calculated using conditional logistic regression. The percent effect change and corresponding CIs were estimated after adjusting for biomarkers shown to be associated with colon cancer risk. After multivariable adjustment, WC was associated with colon cancer risk in men (top vs. bottom tertile RR 1.68, 95% CI 1.06-2.65; ptrend  = 0.02) and in women (RR 1.67, 95% CI 1.09-2.56; ptrend  = 0.03). BMI was associated with risk only in men. The association of WC with colon cancer was accounted mostly for by three biomarkers, high-density lipoprotein cholesterol, non-high-molecular-weight adiponectin and soluble leptin receptor, which in combination explained 46% (95% CI 37-57%) of the association in men and 50% (95% CI 40-65%) of the association in women. Similar results were observed for the associations with BMI in men. These data suggest that alterations in levels of these metabolic biomarkers may represent a primary mechanism of action in the relation of adiposity with colon cancer. Further studies are warranted to determine whether altering their concentrations may reduce colon cancer risk.

  • 3. Allen, Naomi E
    et al.
    Appleby, Paul N
    Key, Timothy J
    Bueno-de-Mesquita, H B
    Ros, Martine M
    Kiemeney, Lambertus A L M
    Tjønneland, Anne
    Roswall, Nina
    Overvad, Kim
    Weikert, Steffen
    Boeing, Heiner
    Chang-Claude, Jenny
    Teucher, Birgit
    Panico, Salvatore
    Sacerdote, Carlotta
    Tumino, Rosario
    Palli, Domenico
    Sieri, Sabina
    Peeters, Petra
    Quirós, Jose Ramón
    Jakszyn, Paula
    Molina-Montes, Esther
    Chirlaque, María-Dolores
    Ardanaz, Eva
    Dorronsoro, Miren
    Khaw, Kay-Tee
    Wareham, Nick
    Ljungberg, Börje
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Biobank Research. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Ehrnström, Roy
    Ericson, Ulrika
    Gram, Inger Torhild
    Parr, Christine L
    Trichopoulou, Antonia
    Karapetyan, Tina
    Dilis, Vardis
    Clavel-Chapelon, Françoise
    Boutron-Ruault, Marie-Christine
    Fagherrazzi, Guy
    Romieu, Isabelle
    Gunter, Marc J
    Riboli, Elio
    Macronutrient intake and risk of urothelial cell carcinoma in the European prospective investigation into cancer and nutrition2013In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 132, no 3, p. 635-644Article in journal (Refereed)
    Abstract [en]

    Previous studies have suggested that dietary factors may be important in the development of bladder cancer. We examined macronutrient intake in relation to risk of urothelial cell carcinoma among 469,339 men and women in the European Prospective Investigation into Cancer and Nutrition. Associations were examined using Cox regression, stratified by sex, age at recruitment and centre and further adjusted for smoking status and duration, body mass index and total energy intake. After an average of 11.3 years of follow-up, 1,416 new cases of urothelial cell carcinoma were identified. After allowing for measurement error, a 3% increase in the consumption of energy intake from animal protein was associated with a 15% higher risk (95% confidence interval [CI]: 3-30%; p(trend) = 0.01) and a 2% increase in energy from plant protein intake was associated with a 23% lower risk (95% CI: 36-7%, p(trend) = 0.006). Dietary intake of fat, carbohydrate, fibre or calcium was not associated with risk. These findings suggest that animal and/or plant protein may affect the risk of urothelial cell carcinoma, and examination of these associations in other studies is needed.

  • 4. Allen, Naomi E
    et al.
    Roddam, Andrew W
    Sieri, Sabina
    Boeing, Heiner
    Jakobsen, Marianne Uhre
    Overvad, Kim
    Tjønneland, Anne
    Halkjær, Jytte
    Vineis, Paolo
    Contiero, Paolo
    Palli, Domenico
    Tumino, Rosario
    Mattiello, Amalia
    Kaaks, Rudolf
    Rohrmann, Sabine
    Trichopoulou, Antonia
    Zilis, Demosthenes
    Koumantaki, Yvoni
    Peeters, Petra H
    Bueno-de-Mesquita, H Bas
    Barricarte, Aurelio
    Rodríguez, Laudina
    Dorronsoro, Miren
    Sánchez, Maria-José
    Chirlaque, María Dolores
    Esquius, Laura
    Manjer, Jonas
    Wallström, Peter
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Ljungberg, Börje
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Bingham, Sheila
    Khaw, Kay-Tee
    Boffetta, Paolo
    Norat, Teresa
    Mouw, Traci
    Riboli, Elio
    A prospective analysis of the association between macronutrient intake and renal cell carcinoma in the European Prospective Investigation into Cancer and Nutrition.2009In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 125, no 4, p. 982-987Article in journal (Refereed)
    Abstract [en]

    Previous case-control studies have suggested that a high intake of animal foods and its associated nutrients are associated with an increased risk of renal cell carcinoma, although data from prospective studies are limited. We report here on the relationship between macronutrient intake and renal cell carcinoma incidence among 435,293 participants enrolled in the European Prospective Investigation into Cancer and Nutrition. Cox proportional hazard models were used to examine the association of dietary intake of fat, protein, carbohydrate, fiber and cholesterol and risk of renal cell carcinoma adjusted for age, sex, center, height, body mass index, physical activity, education, smoking, menopausal status, alcohol and energy intake. During an average 8.8 years of follow-up, 507 renal cell carcinoma cases occurred. Risk of renal cell carcinoma was not associated with macronutrient intake, including nutrients derived from animal sources. Our results indicate that macronutrient intake is not associated with risk of renal cell carcinoma in this cohort of European men and women. (c) 2009 UICC.

  • 5.
    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 University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    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 University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Sustainable Health.
    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 cohort2022In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 152, no 4, p. 725-737Article in journal (Refereed)
    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.

  • 6.
    Andersson, Anne
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Näslund, Ulf
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Tavelin, Björn
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Enblad, Gunilla
    Gustavsson, Anita
    Malmer, Beatrice
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Long-term risk of cardiovascular disease in Hodgkin lymphoma survivors: retrospective cohort analyses and a concept for prospective intervention2009In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 124, no 8, p. 1914-1917Article in journal (Refereed)
    Abstract [en]

    Previous studies have shown increased cardiovascular mortality as late side effects in Hodgkin lymphoma (HL) patients. This study identifies stratifying risk factors for surveillance and defines concepts for a clinical feasible and noninvasive prospective protocol for intervention of cardiovascular side effects. HL patients diagnosed between 1965 and 1995 (n = 6.946) and their first-degree relatives (FDR) were identified through the Swedish Cancer Registry and the Swedish Multigeneration Registry. For the HL and FDR cohort, in-patient care for cardiovascular disease (CVD) was registered through the Hospital Discharge Registry, Sweden. Standard incidence ratios of developing CVD for the HL cohort were calculated. A markedly increased risk for in-patient care of CVD was observed in HL patients with HL diagnosed at age 40 years or younger and with more than 10 years follow-up. In the HL survivors, a family history of congestive heart failure (CHF) and coronary artery disease (CAD) increased the risk for these diseases. The Swedish Hodgkin Intervention and Prevention study started in 2007. In the pilot feasibility study for prospective intervention (47 patients), about 25% of the cases had side effects and laboratory abnormalities. These patients were referred to a cardiologist or general practitioner. In the prospective cohort, a positive family history for CHF or CAD could be a stratifying risk factor when setting up a surveillance model. The prospective on-going study presents an intervention model that screens and treats for comorbidity factors. This article also presents an overview of the study concept.

  • 7. Araghi, Marzieh
    et al.
    Galanti, Maria Rosaria
    Lundberg, Michael
    Lager, Anton
    Engström, Gunnar
    Alfredsson, Lars
    Knutsson, Anders
    Norberg, Margareta
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Sund, Malin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Wennberg, Patrik
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Trolle Lagerros, Ylva
    Bellocco, Rino
    Pedersen, Nancy L.
    Östergren, Per-Olof
    Magnusson, Cecilia
    Use of moist oral snuff (snus) and pancreatic cancer: pooled analysis of nine prospective observational studies2017In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 141, no 4, p. 687-693Article in journal (Refereed)
    Abstract [en]

    While smoking is a well-established risk factor for pancreatic cancer, the effect of smokeless tobacco is less well understood. We used pooled individual data from the Swedish Collaboration on Health Effects of Snus Use to assess the association between Swedish snus use and the risk of pancreatic cancer. A total of 424,152 male participants from nine cohort studies were followed up for risk of pancreatic cancer through linkage to health registers. We used shared frailty models with random effects at the study level, to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) adjusted for confounding factors. During 9,276,054 person-years of observation, 1,447 men developed pancreatic cancer. Compared to never-snus use, current snus use was not associated with risk of pancreatic cancer (HR 0.96, 95% CI 0.83–1.11) after adjustment for smoking. Swedish snus use does not appear to be implicated in the development of pancreatic cancer in men. Tobacco smoke constituents other than nicotine or its metabolites may account for the relationship between smoking and pancreatic cancer.

  • 8. Baglietto, Laura
    et al.
    Ponzi, Erica
    Haycock, Philip
    Hodge, Allison
    Bianca Assumma, Manuela
    Jung, Chol-Hee
    Chung, Jessica
    Fasanelli, Francesca
    Guida, Florence
    Campanella, Gianluca
    Chadeau-Hyam, Marc
    Grankvist, Kjell
    Umeå University, Faculty of Medicine, Department of Biobank Research.
    Johansson, Mikael
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Ala, Ugo
    Provero, Paolo
    Wong, Ee Ming
    Joo, Jihoon
    English, Dallas R
    Kazmi, Nabila
    Lund, Eiliv
    Faltus, Christian
    Kaaks, Rudolf
    Risch, Angela
    Barrdahl, Myrto
    Sandanger, Torkjel M
    Southey, Melissa C
    Giles, Graham G
    Johansson, Mattias
    International Agency for Research on Cancer, Lyon, France.
    Vineis, Paolo
    Polidoro, Silvia
    Relton, Caroline L
    Severi, Gianluca
    DNA methylation changes measured in pre-diagnostic peripheral blood samples are associated with smoking and lung cancer risk2017In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 140, no 1, p. 50-61Article in journal (Refereed)
    Abstract [en]

    DNA methylation changes are associated with cigarette smoking. We used the Illumina Infinium HumanMethylation450 array to determine whether methylation in DNA from pre-diagnostic, peripheral blood samples is associated with lung cancer risk. We used a case-control study nested within the EPIC-Italy cohort and a study within the MCCS cohort as discovery sets (a total of 552 case-control pairs). We validated the top signals in 429 case-control pairs from another 3 studies. We identified six CpGs for which hypomethylation was associated with lung cancer risk: cg05575921 in the AHRR gene (p-valuepooled  = 4 × 10(-17) ), cg03636183 in the F2RL3 gene (p-valuepooled  = 2 × 10 (- 13) ), cg21566642 and cg05951221 in 2q37.1 (p-valuepooled  = 7 × 10(-16) and 1 × 10(-11) respectively), cg06126421 in 6p21.33 (p-valuepooled  = 2 × 10(-15) ) and cg23387569 in 12q14.1 (p-valuepooled  = 5 × 10(-7) ). For cg05951221 and cg23387569 the strength of association was virtually identical in never and current smokers. For all these CpGs except for cg23387569, the methylation levels were different across smoking categories in controls (p-valuesheterogeneity  ≤ 1.8 x10 (- 7) ), were lowest for current smokers and increased with time since quitting for former smokers. We observed a gain in discrimination between cases and controls measured by the area under the ROC curve of at least 8% (p-values ≥ 0.003) in former smokers by adding methylation at the 6 CpGs into risk prediction models including smoking status and number of pack-years. Our findings provide convincing evidence that smoking and possibly other factors lead to DNA methylation changes measurable in peripheral blood that may improve prediction of lung cancer risk.

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  • 9. Bamia, Christina
    et al.
    Lagiou, Pagona
    Jenab, Mazda
    Trichopoulou, Antonia
    Fedirko, Veronika
    Aleksandrova, Krasimira
    Pischon, Tobias
    Overvad, Kim
    Olsen, Anja
    Tjønneland, Anne
    Boutron-Ruault, Marie-Christine
    Fagherazzi, Guy
    Racine, Antoine
    Kuhn, Tilman
    Boeing, Heiner
    Floegel, Anna
    Benetou, Vasiliki
    Palli, Domenico
    Grioni, Sara
    Panico, Salvatore
    Tumino, Rosario
    Vineis, Paolo
    Bueno-de-Mesquita, H B As
    Dik, Vincent K
    Bhoo-Pathy, Nirmala
    Uiterwaal, Cuno S P M
    Weiderpass, Elisabete
    Lund, Eiliv
    Quirós, J Ramón
    Zamora-Ros, Raul
    Molina-Montes, Esther
    Chirlaque, Maria-Dolores
    Ardanaz, Eva
    Dorronsoro, Miren
    Lindkvist, Björn
    Wallström, Peter
    Nilsson, Lena Maria
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research. Umeå University, Arctic Research Centre at Umeå University.
    Sund, Malin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Khaw, Kay-Tee
    Wareham, Nick
    Bradbury, Kathryn E
    Travis, Ruth C
    Ferrari, Pietro
    Duarte-Salles, Talita
    Stepien, Magdalena
    Gunter, Marc
    Murphy, Neil
    Riboli, Elio
    Trichopoulos, Dimitrios
    Coffee, tea and decaffeinated coffee in relation to hepatocellular carcinoma in a European population: multicentre, prospective cohort study2015In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 136, no 8, p. 1899-1908Article in journal (Refereed)
    Abstract [en]

    Inverse associations of coffee and/or tea in relation to hepatocellular carcinoma (HCC) risk have been consistently identified in studies conducted mostly in Asia where consumption patterns of such beverages differ from Europe. In the European Prospective Investigation into Cancer and nutrition (EPIC), we identified 201 HCC cases among 486,799 men/women, after a median follow-up of 11 years. We calculated adjusted hazard ratios (HRs) for HCC incidence in relation to quintiles/categories of coffee/tea intakes. We found that increased coffee and tea intakes were consistently associated with lower HCC risk. The inverse associations were substantial, monotonic and statistically significant. Coffee consumers in the highest compared to the lowest quintile had lower HCC risk by 72% [HR: 0.28; 95% confidence intervals (CIs): 0.16-0.50, p-trend < 0.001]. The corresponding association of tea with HCC risk was 0.41 (95% CI: 0.22-0.78, p-trend = 0.003). There was no compelling evidence of heterogeneity of these associations across strata of important HCC risk factors, including hepatitis B or hepatitis C status (available in a nested case-control study). The inverse, monotonic associations of coffee intake with HCC were apparent for caffeinated (p-trend = 0.009), but not decaffeinated (p-trend = 0.45) coffee for which, however, data were available for a fraction of subjects. Results from this multicentre, European cohort study strengthen the existing evidence regarding the inverse association between coffee/tea and HCC risk. Given the apparent lack of heterogeneity of these associations by HCC risk factors and that coffee/tea are universal exposures, our results could have important implications for high HCC risk subjects.

  • 10. Barrdahl, Myrto
    et al.
    Canzian, Federico
    Lindström, Sara
    Shui, Irene
    Black, Amanda
    Hoover, Robert N
    Ziegler, Regina G
    Buring, Julie E
    Chanock, Stephen J
    Diver, W Ryan
    Gapstur, Susan M
    Gaudet, Mia M
    Giles, Graham G
    Haiman, Christopher
    Henderson, Brian E
    Hankinson, Susan
    Hunter, David J
    Joshi, Amit D
    Kraft, Peter
    Lee, I-Min
    Le Marchand, Loic
    Milne, Roger L
    Southey, Melissa C
    Willett, Walter
    Gunter, Marc
    Panico, Salvatore
    Sund, Malin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Weiderpass, Elisabete
    Sánchez, María-José
    Overvad, Kim
    Dossus, Laure
    Peeters, Petra H
    Khaw, Kay-Tee
    Trichopoulos, Dimitrios
    Kaaks, Rudolf
    Campa, Daniele
    Association of breast cancer risk loci with breast cancer survival2015In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 137, no 12, p. 2837-2845Article in journal (Refereed)
    Abstract [en]

    The survival of breast cancer patients is largely influenced by tumor characteristics, such as TNM stage, tumor grade and hormone receptor status. However, there is growing evidence that inherited genetic variation might affect the disease prognosis and response to treatment. Several lines of evidence suggest that alleles influencing breast cancer risk might also be associated with breast cancer survival. We examined the associations between 35 breast cancer susceptibility loci and the disease over-all survival (OS) in 10,255 breast cancer patients from the National Cancer Institute Breast and Prostate Cancer Cohort Consortium (BPC3) of which 1,379 died, including 754 of breast cancer. We also conducted a meta-analysis of almost 35,000 patients and 5,000 deaths, combining results from BPC3 and the Breast Cancer Association Consortium (BCAC) and performed in silico analyses of SNPs with significant associations. In BPC3, the C allele of LSP1-rs3817198 was significantly associated with improved OS (HRper-allele=0.70; 95% CI: 0.58-0.85; ptrend=2.84 x 10-4; HRheterozygotes=0.71; 95% CI: 0.55-0.92; HRhomozygotes=0.48; 95% CI: 0.31-0.76; p2DF=1.45 x 10-3). In silico, the C allele of LSP1-rs3817198 was predicted to increase expression of the tumor suppressor cyclin-dependent kinase inhibitor 1C (CDKN1C). In the meta-analysis, TNRC9-rs3803662 was significantly associated with increased death hazard (HRMETA =1.09; 95% CI: 1.04-1.15; ptrend=6.6 x 10-4; HRheterozygotes=0.96 95% CI: 0.90-1.03; HRhomozygotes=1.21; 95% CI: 1.09-1.35; p2DF=1.25 x 10-4). In conclusion, we show that there is little overlap between the breast cancer risk single nucleotide polymorphisms (SNPs) identified so far and the SNPs associated with breast cancer prognosis, with the possible exceptions of LSP1-rs3817198 and TNRC9-rs3803662.

    What's new? Genetic factors are known to influence the risk of breast cancer, but inherited genetic variation may also affect disease prognosis and response to treatment. In this study, the we investigated whether single nucleotide polymorphisms (SNPs) that are known to be associated with breast cancer risk might also influence the survival of breast-cancer patients. While two of the investigated SNPs may influence survival, there was otherwise no indication that SNP alleles related to breast cancer risk also play a role in the survival of breast cancer patients.

  • 11.
    Bergqvist, Michael
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology. Center for Research & Development, Uppsala University, County Council of Gävleborg, Gävle Hospital, Gävle, Sweden.
    Christensen, Helene N.
    Wiklund, Fredrik
    Bergström, Stefan
    Real world utilization of EGFR TKIs and prognostic factors for survival in NSCLC during 2010-2016 in Sweden: A nationwide observational study2020In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 146, no 9, p. 2510-2517Article in journal (Refereed)
    Abstract [en]

    The purpose of our study was to investigate time trends in treatment pattern and prognostic factors for overall survival (OS) in epidermal growth factor receptor (EGFR) targeting tyrosine kinase inhibitors (TKIs) treated nonsmall cell lung cancer (NSCLC) patients. Utilizing Swedish nationwide registers, we identified all Stage IIIB-IV NSCLC patients treated with EGFR TKIs and followed them from diagnosis (2010-2015) until death or end of observation (2016). Multivariable Cox regression analyses were performed to test associations of patient-, tumor-related factors with OS. Of 9,992 Stage IIIB-IV NSCLC patients, the 1,419 (14%) who initiated EGFR TKI treatment during observation were younger (median age 68 vs. 71 years), less >= 1 comorbidities (34% vs. 46%), more often female (59% vs. 47%), Stage IV (89% vs. 85%) and adenocarcinoma (85% vs. 66%) compared to non-TKI treated patients. After TKI initiation, 7% (n = 100) of the patients switched, 4% (n = 62) rechallenged a TKI treatment, 65% (n = 919) discontinued and 24% (n = 338) had died. A more recent diagnosis demonstrated shorter time to EGFR TKI initiation, prolonged treatment length and longer median OS (15.3 months 2010-2011; 14.4 months 2012-2013; 18.6 months 2014-2015). Prognostic factors for longer OS when treated with EGFR TKIs were younger age, adenocarcinoma, less advanced clinical stage and less comorbid disease. In conclusion, during the observation period, survival improved for EGFR TKI treated NSCLC patients, as did the accessibility for targeted therapies for these patients.

  • 12. Borena, Wegene
    et al.
    Strohmaier, Susanne
    Lukanova, Annekatrin
    Bjørge, Tone
    Lindkvist, Björn
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Edlinger, Michael
    Stocks, Tanja
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Nagel, Gabriele
    Manjer, Jonas
    Engeland, Anders
    Selmer, Randi
    Häggström, Christel
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Tretli, Steinar
    Concin, Hans
    Jonsson, Håkan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Stattin, Pär
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Ulmer, Hanno
    Metabolic risk factors and primary liver cancer in a prospective study of 578,700 adults2012In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 131, no 1, p. 193-200Article in journal (Refereed)
    Abstract [en]

    Initial studies have indicated diabetes and obesity to be risk factors for hepatocellular carcinoma; but the association between other metabolic risk factors and primary liver cancer (PLC) has not been investigated. The metabolic syndrome and cancer project (Me-Can) includes cohorts from Norway, Austria and Sweden with data on 578,700 subjects. We used Cox proportional hazard models to calculate relative risks (RRs) of PLC by body mass index (BMI), blood pressure and plasma levels of glucose, cholesterol and triglycerides as continuous standardized variables (z-score with mean = 0 and standard deviation (SD) = 1) and their standardized sum of metabolic syndrome (MetS) z-score. RRs were corrected for random error in measurements. During an average follow-up of 12.0 years (SD = 7.8), 266 PLCs were diagnosed among cohort members. RR of liver cancer per unit increment of z-score adjusted for age, smoking status and BMI and stratified by birth year, sex and sub-cohorts, was for BMI 1.39 (95% confidence interval (CI) 1.24-1.58), mid blood pressure 2.08 (0.95-4.73), blood glucose 2.13 (1.55-2.94) cholesterol 0.62 (0.51-0.76) and serum triglycerides 0.85 (0.65-1.10). The RR per one unit increment of the MetS z-score was 1.35 (1.12-1.61). BMI, glucose and a composite MetS score were positively and cholesterol negatively associated with risk of liver cancer.

  • 13. Bosse, Yohan
    et al.
    Li, Zhonglin
    Xia, Jun
    Manem, Venkata
    Carreras-Torres, Robert
    Gabriel, Aurelie
    Gaudreault, Nathalie
    Albanes, Demetrius
    Aldrich, Melinda C.
    Andrew, Angeline
    Arnold, Susanne
    Bickeboeller, Heike
    Bojesen, Stig E.
    Brennan, Paul
    Brunnstrom, Hans
    Caporaso, Neil
    Chen, Chu
    Christiani, David C.
    Field, John K.
    Goodman, Gary
    Grankvist, Kjell
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Houlston, Richard
    Johansson, Mattias
    Johansson, Mikael
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Kiemeney, Lambertus A.
    Lam, Stephen
    Landi, Maria T.
    Lazarus, Philip
    Le Marchand, Loic
    Liu, Geoffrey
    Melander, Olle
    Rennert, Gadi
    Risch, Angela
    Rosenberg, Susan M.
    Schabath, Matthew B.
    Shete, Sanjay
    Song, Zhuoyi
    Stevens, Victoria L.
    Tardon, Adonina
    Wichmann, H-Erich
    Woll, Penella
    Zienolddiny, Shan
    Obeidat, Ma'en
    Timens, Wim
    Hung, Rayjean J.
    Joubert, Philippe
    Amos, Christopher I.
    McKay, James D.
    Transcriptome-wide association study reveals candidate causal genes for lung cancer2020In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 146, no 7, p. 1862-1878Article in journal (Refereed)
    Abstract [en]

    We have recently completed the largest GWAS on lung cancer including 29,266 cases and 56,450 controls of European descent. The goal of our study has been to integrate the complete GWAS results with a large‐scale expression quantitative trait loci (eQTL) mapping study in human lung tissues (n = 1,038) to identify candidate causal genes for lung cancer. We performed transcriptome‐wide association study (TWAS) for lung cancer overall, by histology (adenocarcinoma, squamous cell carcinoma and small cell lung cancer) and smoking subgroups (never‐ and ever‐smokers). We performed replication analysis using lung data from the Genotype‐Tissue Expression (GTEx) project. DNA damage assays were performed in human lung fibroblasts for selected TWAS genes. As expected, the main TWAS signal for all histological subtypes and ever‐smokers was on chromosome 15q25. The gene most strongly associated with lung cancer at this locus using the TWAS approach was IREB2 (pTWAS = 1.09E−99), where lower predicted expression increased lung cancer risk. A new lung adenocarcinoma susceptibility locus was revealed on 9p13.3 and associated with higher predicted expression of AQP3 (pTWAS = 3.72E−6). Among the 45 previously described lung cancer GWAS loci, we mapped candidate target gene for 17 of them. The association AQP3‐adenocarcinoma on 9p13.3 was replicated using GTEx (pTWAS = 6.55E−5). Consistent with the effect of risk alleles on gene expression levels, IREB2 knockdown and AQP3 overproduction promote endogenous DNA damage. These findings indicate genes whose expression in lung tissue directly influences lung cancer risk.

  • 14. Botteri, E.
    et al.
    Ferrari, P.
    Roswall, N.
    Tjonneland, A.
    Hjartaker, A.
    Huerta, J. M.
    Fortner, R. T.
    Trichopoulou, A.
    Karakatsani, A.
    La Vecchia, C.
    Pala, V.
    Perez-Cornago, A.
    Sonestedt, E.
    Liedberg, F.
    Overvad, K.
    Sanchez, M. J.
    Gram, I. T.
    Stepien, M.
    Trijsburg, L.
    Ljungberg, Börje
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Johansson, M.
    Umeå University, Faculty of Medicine, Department of Biobank Research.
    Kuehn, T.
    Panico, S.
    Tumino, R.
    Bueno-de-Mesquita, H. B.
    Weiderpass, E.
    Alcohol consumption and risk of urothelial cell bladder cancer in the European prospective investigation into cancer and nutrition cohort2017In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 141, no 10, p. 1963-1970Article in journal (Refereed)
    Abstract [en]

    Findings on the association between alcohol consumption and bladder cancer are inconsistent. We investigated that association in the European Prospective Investigation into Cancer and Nutrition cohort. We included 476,160 individuals mostly aged 35-70 years, enrolled in ten countries and followed for 13.9 years on average. Hazard ratios (HR) for developing urothelial cell carcinoma (UCC; 1,802 incident cases) were calculated using Cox proportional hazards models. Alcohol consumption at baseline and over the life course was analyzed, as well as different types of beverages (beer, wine, spirits). Baseline alcohol intake was associated with a statistically nonsignificant increased risk of UCC (HR 1.03; 95% confidence interval (CI) 1.00-1.06 for each additional 12 g/day). HR in smokers was 1.04 (95% CI 1.01-1.07). Men reporting high baseline intakes of alcohol (>96 g/day) had an increased risk of UCC (HR 1.57; 95% CI 1.03-2.40) compared to those reporting moderate intakes (<6 g/day), but no dose-response relationship emerged. In men, an increased risk of aggressive forms of UCC was observed even at lower doses (>6 to 24 g/day). Average lifelong alcohol intake was not associated with the risk of UCC, however intakes of spirits>24 g/day were associated with an increased risk of UCC in men (1.38; 95% CI 1.01-1.91) and smokers (1.39; 95% CI 1.01-1.92), compared to moderate intakes. We found no association between alcohol and UCC in women and never smokers. In conclusion, we observed some associations between alcohol and UCC in men and in smokers, possibly because of residual confounding by tobacco smoking.

  • 15. Bradbury, Kathryn E.
    et al.
    Appleby, Paul N.
    Tipper, Sarah J.
    Travis, Ruth C.
    Allen, Naomi E
    Kvaskoff, Marina
    Overvad, Kim
    Tjønneland, Anne
    Halkjaer, Jytte
    Cervenka, Iris
    Mahamat-Saleh, Yahya
    Bonnet, Fabrice
    Kaaks, Rudolf
    Fortner, Renée T.
    Boeing, Heiner
    Trichopoulou, Antonia
    La Vecchia, Carlo
    Stratigos, Alexander J.
    Palli, Domenico
    Grioni, Sara
    Matullo, Giuseppe
    Panico, Salvatore
    Tumino, Rosario
    Peeters, Petra H.
    Bueno-de-Mesquita, H Bas
    Ghiasvand, Reza
    Veierød, Marit B.
    Weiderpass, Elisabete
    Bonet, Catalina
    Molina, Elena
    Huerta, José M.
    Larrañaga, Nerea
    Barricarte, Aurelio
    Merino, Susana
    Isaksson, Karolin
    Stocks, Tanja
    Ljuslinder, Ingrid
    Hemmingsson, Oskar
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Wareham, Nick
    Khaw, Kay-Tee
    Gunter, Marc J.
    Rinaldi, Sabina
    Tsilidis, Konstantinos K.
    Aune, Dagfinn
    Riboli, Elio
    Key, Timothy J.
    Circulating insulin-like growth factor I in relation to melanoma risk in the European prospective investigation into cancer and nutrition2019In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 144, no 5, p. 957-966Article in journal (Refereed)
    Abstract [en]

    Insulin-like growth factor-I (IGF-I) regulates cell proliferation and apoptosis, and is thought to play a role in tumour development. Previous prospective studies have shown that higher circulating concentrations of IGF-I are associated with a higher risk of cancers at specific sites, including breast and prostate. No prospective study has examined the association between circulating IGF-I concentrations and melanoma risk. A nested case-control study of 1,221 melanoma cases and 1,221 controls was performed in the European Prospective Investigation into Cancer and Nutrition cohort, a prospective cohort of 520,000 participants recruited from 10 European countries. Conditional logistic regression was used to estimate odds ratios (ORs) for incident melanoma in relation to circulating IGF-I concentrations, measured by immunoassay. Analyses were conditioned on the matching factors and further adjusted for age at blood collection, education, height, BMI, smoking status, alcohol intake, marital status, physical activity and in women only, use of menopausal hormone therapy. There was no significant association between circulating IGF-I concentration and melanoma risk (OR for highest vs lowest fifth = 0.93 [95% confidence interval [CI]: 0.71 to 1.22]). There was no significant heterogeneity in the association between IGF-I concentrations and melanoma risk when subdivided by gender, age at blood collection, BMI, height, age at diagnosis, time between blood collection and diagnosis, or by anatomical site or histological subtype of the tumour (Pheterogeneity≥0.078). We found no evidence for an association between circulating concentrations of IGF-I measured in adulthood and the risk of melanoma.

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  • 16. Buckland, G
    et al.
    Ros, M M
    Roswall, N
    Bueno-de-Mesquita, H B
    Travier, N
    Tjonneland, A
    Kiemeney, L A
    Sacerdote, C
    Tumino, R
    Ljungberg, Börje
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Gram, I T
    Weiderpass, E
    Skeie, G
    Malm, J
    Ehrnström, R
    Chang-Claude, J
    Mattiello, A
    Agnoli, C
    Peeters, P H
    Boutron-Ruault, M C
    Fagherazzi, G
    Clavel-Chapelon, F
    Nilsson, Lena Maria
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Amiano, P
    Trichopoulou, A
    Oikonomou, E
    Tsiotas, K
    Sánchez, M J
    Overvad, K
    Quirós, J R
    Chirlaque, M D
    Barricarte, A
    Key, T J
    Allen, N E
    Khaw, K T
    Wareham, N
    Riboli, E
    Kaaks, R
    Boeing, H
    Palli, D
    Romieu, I
    Romaguera, D
    Gonzalez, C A
    Adherence to the Mediterranean diet and risk of bladder cancer in the EPIC cohort study2014In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 134, no 10, p. 2504-2511Article in journal (Refereed)
    Abstract [en]

    There is growing evidence of the protective role of the Mediterranean diet (MD) on cancer. However, to date no epidemiological study has investigated the influence of the MD on bladder cancer. We evaluated the association between adherence to the MD and risk of urothelial cell bladder cancer (UCC), according to tumor aggressiveness, in the European Prospective Investigation into Cancer and Nutrition (EPIC). The analysis included 477,312 participants, recruited from ten European countries between 1991 and 2000. Information from validated dietary questionnaires was used to develop a relative Mediterranean diet score (rMED), including nine dietary components. Cox regression models were used to assess the effect of the rMED on UCC risk, while adjusting for dietary energy and tobacco smoking of any kind. Stratified analyses were performed by sex, BMI, smoking status, European region and age at diagnosis. During an average follow-up of 11 years, 1,425 participants (70.9% male) were diagnosed with a first primary UCC. There was a negative but non-significant association between a high versus low rMED score and risk of UCC overall (HR: 0.84 [95% CI 0.69, 1.03]) and risk of aggressive (HR: 0.88 [95% CI 0.61, 1.28]) and non-aggressive tumors (HR: 0.78 [95% CI 0.54, 1.14]). Although there was no effect modification in the stratified analyses, there was a significant 34% (p = 0.043) decreased risk of UCC in current smokers with a high rMED score. In EPIC, the MD was not significantly associated with risk of UCC, although we cannot exclude that a MD may reduce risk in current smokers.

  • 17. Buckland, G
    et al.
    Travier, N
    Cottet, V
    Gonzalez, CA
    Lujan-Barroso, L
    Agudo, A
    Trichopoulou, A
    Lagiou, P
    Trichopoulos, D
    Peeters, PH
    May, A
    Bueno-de-Mesquita, HB
    Duijnhoven, FJ Bvan
    Key, TJ
    Allen, N
    Khaw, KT
    Wareham, N
    Romieu, I
    McCormack, V
    Boutron-Ruault, M
    Clavel-Chapelon, F
    Panico, S
    Agnoli, C
    Palli, D
    Tumino, R
    Vineis, P
    Amiano, P
    Barricarte, A
    Rodriguez, L
    Sanchez, MJ
    Chirlaque, MD
    Kaaks, R
    Teucher, B
    Boeing, H
    Bergmann, MM
    Overvad, K
    Dahm, CC
    Tjonneland, A
    Olsen, A
    Manjer, J
    Wirfalt, E
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research. Umeå University, Faculty of Medicine, Department of Biobank Research.
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology, School of Dentistry.
    Lund, E
    Hjartaker, A
    Skeie, G
    Vergnaud, AC
    Norat, T
    Romaguera, D
    Riboli, E
    Adherence to the mediterranean diet and risk of breast cancer in the European prospective investigation into cancer and nutrition cohort study2013In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 132, no 12, p. 2918-2927Article in journal (Refereed)
    Abstract [en]

    Epidemiological evidence suggests that the Mediterranean diet (MD) could reduce the risk of breast cancer (BC). As evidence from the prospective studies remains scarce and conflicting, we investigated the association between adherence to the MD and risk of BC among 335,062 women recruited from 1992 to 2000, in ten European countries, and followed for 11 years on average. Adherence to the MD was estimated through an adapted relative Mediterranean diet (arMED) score excluding alcohol. Cox proportional hazards regression models were used while adjusting for BC risk factors. A total of 9,009 postmenopausal and 1,216 premenopausal first primary incident invasive BC were identified (5,862 estrogen or progesterone receptor positive [ER+/PR+] and 1,018 estrogen and progesterone receptor negative [ER/PR]). The arMED was inversely associated with the risk of BC overall and in postmenopausal women (high vs. low arMED score; hazard ratio [HR] = 0.94 [95% confidence interval [CI]: 0.88, 1.00] ptrend = 0.048, and HR = 0.93 [95% CI: 0.87, 0.99] ptrend = 0.037, respectively). The association was more pronounced in ER/PR tumors (HR = 0.80 [95% CI: 0.65, 0.99] ptrend = 0.043). The arMED score was not associated with BC in premenopausal women. Our findings show that adherence to a MD excluding alcohol was related to a modest reduced risk of BC in postmenopausal women, and this association was stronger in receptor-negative tumors. The results support the potential scope for BC prevention through dietary modification.

  • 18. Buckland, G.
    et al.
    Travier, N.
    Huerta, J. M.
    Bueno-de-Mesquita, H. B(As)
    Siersema, P. D.
    Skeie, G.
    Weiderpass, E.
    Engeset, D.
    Ericson, U.
    Ohlsson, B.
    Agudo, A.
    Romieu, I.
    Ferrari, P.
    Freisling, H.
    Colorado-Yohar, S.
    Li, K.
    Kaaks, R.
    Pala, V.
    Cross, A. J.
    Riboli, E.
    Trichopoulou, A.
    Lagiou, P.
    Bamia, C.
    Boutron-Ruault, M. C.
    Fagherazzi, G.
    Dartois, L.
    May, A. M.
    Peeters, P. H.
    Panico, S.
    Johansson, Mattias
    Umeå University, Faculty of Medicine, Department of Biobank Research. International Agency for Research on Cancer (IARC-WHO), France.
    Wallner, Bengt
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Palli, D.
    Key, T. J.
    Khaw, K. T.
    Ardanaz, E.
    Overvad, K.
    Tjonneland, A.
    Dorronsoro, M.
    Sanchez, M. J.
    Quiros, J. R.
    Naccarati, A.
    Tumino, R.
    Boeing, H.
    Gonzalez, C. A.
    Healthy lifestyle index and risk of gastric adenocarcinoma in the EPIC cohort study2015In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 137, no 3, p. 598-606Article in journal (Refereed)
    Abstract [en]

    Several modifiable lifestyle factors, including smoking, alcohol, certain dietary factors and weight are independently associated with gastric cancer (GC); however, their combined impact on GC risk is unknown. We constructed a healthy lifestyle index to investigate the joint influence of these behaviors on GC risk within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. The analysis included 461,550 participants (662 first incident GC cases) with a mean follow-up of 11.4 years. A healthy lifestyle index was constructed, assigning 1 point for each healthy behavior related to smoking status, alcohol consumption and diet quality (represented by the Mediterranean diet) for assessing overall GC and also body mass index for cardia GC and 0 points otherwise. Risk of GC was calculated using Cox proportional hazards regression models while adjusting for relevant confounders. The highest versus lowest score in the healthy lifestyle index was associated with a significant lower risk of GC, by 51% overall (HR 0.49 95% CI 0.35, 0.70), by 77% for cardia GC (HR 0.23 95% CI 0.08, 0.68) and by 47% for noncardia GC (HR 0.53 (95% CI 0.32, 0.87), p-trends<0.001. Population attributable risk calculations showed that 18.8% of all GC and 62.4% of cardia GC cases could have been prevented if participants in this population had followed the healthy lifestyle behaviors of this index. Adopting several healthy lifestyle behaviors including not smoking, limiting alcohol consumption, eating a healthy diet and maintaining a normal weight is associated with a large decreased risk of GC. What's new? Several modifiable lifestyle factors, including smoking status, alcohol consumption, diet quality and weight, have been independently associated with gastric cancer. Behavioral patterns often cluster, however, lifestyle scores can be used to analyse overlapping risk factors. In this study, the authors used a healthy-lifestyle index to evaluate the combined effects of all of the above factors on the risk of developing gastric cancer (GC). They found that following a healthy lifestyle dramatically decreases the burden of gastric cancer.

  • 19.
    Bulliard, Jean-Luc
    et al.
    Centre for Primary Care and Public Health (unisanté), University of Lausanne, Lausanne, Switzerland.
    Beau, Anna-Belle
    Pharmacologie Médicale, Faculté de Médecine, Université Paul-Sabatier III, CHU Toulouse, UMR INSERM, Toulouse, France.
    Njor, Sisse
    Randers Regional Hospital, Randers, Denmark; Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
    Wu, Wendy Yi-Ying
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Procopio, Pietro
    Daffodil Centre, University of Sydney, a joint venture with Cancer Council New South Wales, Sydney, Australia; Melbourne School of Population and Global Health, University of Melbourne, Carlton, Australia.
    Nickson, Carolyn
    Daffodil Centre, University of Sydney, a joint venture with Cancer Council New South Wales, Sydney, Australia; Melbourne School of Population and Global Health, University of Melbourne, Carlton, Australia.
    Lynge, Elsebeth
    Nykøbing Falster Hospital, University of Copenhagen, Nykøbing Falster, Denmark.
    Breast cancer screening and overdiagnosis2021In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 149, no 4, p. 846-853Article in journal (Refereed)
    Abstract [en]

    Overdiagnosis is a harmful consequence of screening which is particularly challenging to estimate. An unbiased setting to measure overdiagnosis in breast cancer screening requires comparative data from a screened and an unscreened cohort for at least 30 years. Such randomised data will not become available, leaving us with observational data over shorter time periods and outcomes of modelling. This collaborative effort of the International Cancer Screening Network quantified the variation in estimated breast cancer overdiagnosis in organised programmes with evaluation of both observed and simulated data, and presented examples of how modelling can provide additional insights. Reliable observational data, analysed with study design accounting for methodological pitfalls, and modelling studies with different approaches, indicate that overdiagnosis accounts for less than 10% of invasive breast cancer cases in a screening target population of women aged 50 to 69. Estimates above this level are likely to derive from inaccuracies in study design. The widely discrepant estimates of overdiagnosis reported from observational data could substantially be reduced by use of a cohort study design with at least 10 years of follow-up after screening stops. In contexts where concomitant opportunistic screening or gradual implementation of screening occurs, and data on valid comparison groups are not readily available, modelling of screening intervention becomes an advantageous option to obtain reliable estimates of breast cancer overdiagnosis.

  • 20. Büchner, Frederike L
    et al.
    Bueno-de-Mesquita, H Bas
    Ros, Martine M
    Kampman, Ellen
    Egevad, Lars
    Overvad, Kim
    Raaschou-Nielsen, Ole
    Tjønneland, Anne
    Roswall, Nina
    Clavel-Chapelon, Francoise
    Boutron-Ruault, Marie-Christine
    Touillaud, Marina
    Chang-Claude, Jenny
    Kaaks, Rudolf
    Boeing, Heiner
    Weikert, Steffen
    Trichopoulou, Antonia
    Lagiou, Pagona
    Trichopoulos, Dimitrios
    Palli, Domenico
    Sieri, Sabina
    Vineis, Paolo
    Tumino, Rosario
    Panico, Salvatore
    Vrieling, Alina
    Peeters, Petra H M
    van Gils, Carla H
    Lund, Eiliv
    Gram, Inger T
    Engeset, Dagrun
    Martinez, Carmen
    Gonzalez, Carlos A
    Larrañaga, Nerea
    Ardanaz, Eva
    Navarro, Carmen
    Rodríguez, Laudina
    Manjer, Jonas
    Ehrnström, Roy A
    Hallmans, Goran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Ljungberg, Borje
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Allen, Naomi E
    Roddam, Andrew W
    Bingham, Sheila
    Khaw, Kay-Tee
    Slimani, Nadia
    Boffetta, Paolo
    Jenab, Mazda
    Mouw, Traci
    Michaud, Dominique S
    Kiemeney, Lambertus A L M
    Riboli, Elio
    Consumption of vegetables and fruit and the risk of bladder cancer in the European Prospective Investigation into Cancer and Nutrition2009In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 125, no 11, p. 2643-2651Article in journal (Refereed)
    Abstract [en]

    Previous epidemiologic studies found inconsistent associations between vegetables and fruit consumption and the risk of bladder cancer. We therefore investigated the association between vegetable and fruit consumption and the risk of bladder cancer among participants of the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Data on food consumption and complete follow-up for cancer occurrence was available for a total of 478,533 participants, who were recruited in 10 European countries. Estimates of rate ratios were obtained by Cox proportional hazard models, stratified by age at recruitment, gender and study centre, and adjusted for total energy intake, smoking status, duration of smoking and lifetime intensity of smoking. A calibration study in a subsample was used to control for dietary measurement errors. After a mean follow-up of 8.7 years, 1015 participants were newly diagnosed with bladder cancer. Increments of 100 g/day in fruit and vegetable consumption combined did not affect bladder cancer risk (i.e., calibrated HR = 0.98; 95%CI: 0.95-1.01). Borderline statistically significant lower bladder cancer risks were found among never smokers with increased consumption of fruit and vegetables combined (HR = 0.94 95%CI: 0.87-1.00 with increments of 100 g/day; calibrated HR = 0.92 95%CI 0.79-1.06) and increased consumption of apples and pears (hard fruit; calibrated HR = 0.90 95%CI: 0.82-0.98 with increments of 25 g/day). For none of the associations a statistically significant interaction with smoking status was found. Our findings do not support an effect of fruit and vegetable consumption, combined or separately, on bladder cancer risk. (c) 2009 UICC.

  • 21.
    Büchner, Frederike L
    et al.
    The National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands.
    Bueno-de-Mesquita, H Bas
    The National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands.
    Ros, Martine M
    The National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands.
    Kampman, Ellen
    Department of Epidemiology, Biostatistics and HTA, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
    Egevad, Lars
    Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
    Overvad, Kim
    Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
    Tjønneland, Anne
    Institute of Cancer Epidemiology, Danish Cancer Society, Copenhagen, Denmark.
    Roswall, Nina
    Institute of Cancer Epidemiology, Danish Cancer Society, Copenhagen, Denmark.
    Clavel-Chapelon, Françoise
    INSERM (Institut National de la Santé et de la Recherche Médicale), ERI 20/Université Paris-Sud, EA 4045, IFR 69/Institut Gustave-Roussy, Villejuif, France.
    Boutron-Ruault, Marie-Christine
    INSERM (Institut National de la Santé et de la Recherche Médicale), ERI 20/Université Paris-Sud, EA 4045, IFR 69/Institut Gustave-Roussy, Villejuif, France.
    Touillaud, Marina
    INSERM (Institut National de la Santé et de la Recherche Médicale), ERI 20/Université Paris-Sud, EA 4045, IFR 69/Institut Gustave-Roussy, Villejuif, France.
    Kaaks, Rudolf
    Division of Clinical Epidemiology, Deutsches Krebsforschungszentrum, Heidelberg, Germany.
    Chang-Claude, Jenny
    Division of Clinical Epidemiology, Deutsches Krebsforschungszentrum, Heidelberg, Germany.
    Boeing, Heiner
    German Institute of Human Nutrition, Potsdam-Rehbücke, Germany.
    Weikert, Steffen
    German Institute of Human Nutrition, Potsdam-Rehbücke, Germany.
    Trichopoulou, Antonia
    Department of Hygiene, Epidemiology and Medical Statistics, Medical School, University of Athens, Athens, Greece.
    Naska, Ada
    Department of Hygiene, Epidemiology and Medical Statistics, Medical School, University of Athens, Athens, Greece.
    Benetou, Vicky
    Department of Hygiene, Epidemiology and Medical Statistics, Medical School, University of Athens, Athens, Greece.
    Palli, Domenico
    Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute (ISPO), Florence, Italy.
    Sieri, Sabina
    Nutritional Epidemiology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy.
    Vineis, Paolo
    Cancer Epidemiology Department, University of Turin, Turin, Italy.
    Tumino, Rosario
    Cancer Registry and Histopathology Unit, Department of Oncology, “Civile M.P. Arezzo” Hospital, Ragusa, Italy.
    Panico, Salvatore
    Department of Clinical and Experimental Medicine, Federico II University, Medical School, Naples, Italy.
    van Duijnhoven, Fränzel J B
    The National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands.
    Peeters, Petra H M
    Department of Epidemiology and Public Health, Imperial College London, London, UK.
    van Gils, Carla H
    Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands.
    Lund, Eiliv
    Institute of Community Medicine, University of Tromso, Tromso, Norway.
    Gram, Inger T
    Institute of Community Medicine, University of Tromso, Tromso, Norway.
    Sánchez, Maria-José
    Andalusian School of Public Health and CIBER de Epidemiología y Salud Pública (CIBERESP), Granada, Spain.
    Jakszyn, Paula
    Unit of Nutrition, Environment and Cancer, Cancer Epidemiology Research Programme, Catalan Institute of Oncology (ICO), Barcelona, Spain.
    Larrañaga, Nerea
    Public Health Department of Gipuzkoa, Basque Government and CIBER de Epidemiologia y Salud Pública (CIBERESP), San Sebastian, Spain.
    Ardanaz, Eva
    Public Health Institute of Navarra and CIBER Epidemiología y Salud Pública (CIBERESP), Pamplona, Spain.
    Navarro, Carmen
    Epidemiology Department, Murcia Health Council and CIBER Epidemiología y Salud Pública (CIBERESP), Murcia, Spain.
    Rodríguez, Laudina
    Public Health and Participation Directorate, Health and Health Care Services Council, Asturias, Spain.
    Manjer, Jonas
    Department of Surgery, Malmö University Hospital, Lund University, Malmö, Sweden.
    Ehrnström, Roy
    Department of Pathology, Malmö University Hospital, Lund University, Malmö, Sweden.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Ljungberg, Börje
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Key, Tim J
    Cancer Epidemiology Unit, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK.
    Allen, Naomi E
    Cancer Epidemiology Unit, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK.
    Khaw, Kay-Tee
    Department of Public Health and Primary Care, University of Cambridge School of Clinical Medicine, Cambridge, UK.
    Wareham, Nicholas
    Department of Public Health and Primary Care, University of Cambridge School of Clinical Medicine, Cambridge, UK.
    Slimani, Nadia
    International Agency for Research on Cancer, Lyon, France.
    Jenab, Mazda
    International Agency for Research on Cancer, Lyon, France.
    Boffetta, Paolo
    International Agency for Research on Cancer, Lyon, France.
    Kiemeney, Lambertus A L M
    Department of Urology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
    Riboli, Elio
    Department of Epidemiology and Public Health, Imperial College London, London, UK.
    Variety in vegetable and fruit consumption and risk of bladder cancer in the European prospective investigation into cancer and nutrition2011In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 128, no 12, p. 2971-2979Article in journal (Refereed)
    Abstract [en]

    Recent research does not show an association between fruit and vegetable consumption and bladder cancer risk. None of these studies investigated variety in fruit and vegetable consumption, which may capture different aspects of consumption. We investigated whether a varied consumption of vegetables and fruits is associated with bladder cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Detailed data on food consumption and complete follow-up for cancer incidence were available for 452,185 participants, who were recruited from ten European countries. After a mean follow-up of 8.7 years, 874 participants were diagnosed with bladder cancer. Diet diversity scores (DDSs) were used to quantify the variety in fruit and vegetable consumption. Multivariable Cox proportional hazard models were used to assess the effect of the DDSs on bladder cancer risk. There was no evidence of a statistically significant association between bladder cancer risk and any of the DDSs when these scores were considered as continuous covariates. However, the hazard ratio (HR) for the highest tertile of the DDS for combined fruit and vegetable consumption was marginally significant compared to the lowest (HR = 1.30, 95% confidence interval: 1.00-1.69, p-trend = 0.05). In EPIC, there is no clear association between a varied fruit and vegetable consumption and bladder cancer risk. This finding provides further evidence for the absence of any strong association between fruit and vegetable consumption as measured by a food frequency questionnaire and bladder cancer risk.

  • 22. Caini, Saverio
    et al.
    Masala, Giovanna
    Saieva, Calogero
    Kvaskoff, Marina
    Sacerdote, Carlotta
    Savoye, Isabelle
    Hemmingsson, Oskar
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Bech, Bodil Hammer
    Overvad, Kim
    Tjonneland, Anne
    Petersen, Kristina E. N.
    Mancini, Francesca Romana
    Boutron-Ruault, Marie-Christine
    Cervenka, Iris
    Kaaks, Rudolf
    Kuehn, Tilman
    Boeing, Heiner
    Floegel, Anna
    Trichopoulou, Antonia
    Valanou, Elisavet
    Kritikou, Maria
    Tagliabue, Giovanna
    Panico, Salvatore
    Tumino, Rosario
    Bueno-de-Mesquita, H. B(as)
    Peeters, Petra H.
    Veierod, Marit B.
    Ghiasvand, Reza
    Lukic, Marko
    Ramon Quiros, Jose
    Chirlaque, Maria-Dolores
    Ardanaz, Eva
    Salamanca Fernandez, Elena
    Larranaga, Nerea
    Zamora-Ros, Raul
    Nilsson, Lena Maria
    Umeå University, Arctic Research Centre at Umeå University. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Ljuslinder, Ingrid
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Jirstrom, Karin
    Sonestedt, Emily
    Key, Timothy J.
    Wareham, Nick
    Khaw, Kay-Tee
    Gunter, Marc
    Huybrechts, Inge
    Murphy, Neil
    Tsilidis, Konstantinos K.
    Weiderpass, Elisabete
    Palli, Domenico
    Coffee, tea and melanoma risk: findings from the European Prospective Investigation into Cancer and Nutrition2017In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 140, no 10, p. 2246-2255Article in journal (Refereed)
    Abstract [en]

    What's new? Laboratory studies suggest that coffee and tea protect against melanoma, but epidemiological findings are inconsistent. Here the authors studied more than 400,000 participants within the European Prospective Investigation into Cancer and Nutrition (EPIC) and confirmed an inverse association between caffeinated coffee consumption and melanoma risk. No association was found with decaffeinated coffee or tea. Interestingly, drinking coffee only protected men, but not women, from developing the often fatal skin cancer, raising interesting questions about gender-specific hormones or coffee habits influencing this association. In vitro and animal studies suggest that bioactive constituents of coffee and tea may have anticarcinogenic effects against cutaneous melanoma; however, epidemiological evidence is limited to date. We examined the relationships between coffee (total, caffeinated or decaffeinated) and tea consumption and risk of melanoma in the European Prospective Investigation into Cancer and Nutrition (EPIC). EPIC is a multicentre prospective study that enrolled over 500,000 participants aged 25-70 years from ten European countries in 1992-2000. Information on coffee and tea drinking was collected at baseline using validated country-specific dietary questionnaires. We used adjusted Cox proportional hazards regression models to calculate hazard ratios (HR) and 95% confidence intervals (95% CI) for the associations between coffee and tea consumption and melanoma risk. Overall, 2,712 melanoma cases were identified during a median follow-up of 14.9 years among 476,160 study participants. Consumption of caffeinated coffee was inversely associated with melanoma risk among men (HR for highest quartile of consumption vs. non-consumers 0.31, 95% CI 0.14-0.69) but not among women (HR 0.96, 95% CI 0.62-1.47). There were no statistically significant associations between consumption of decaffeinated coffee or tea and the risk of melanoma among both men and women. The consumption of caffeinated coffee was inversely associated with melanoma risk among men in this large cohort study. Further investigations are warranted to confirm our findings and clarify the possible role of caffeine and other coffee compounds in reducing the risk of melanoma.

  • 23. Castellsagué, Xavier
    et al.
    Pawlita, Michael
    Roura, Esther
    Margall, Núria
    Waterboer, Tim
    Bosch, F Xavier
    de Sanjosé, Silvia
    Gonzalez, Carlos Alberto
    Dillner, Joakim
    Gram, Inger T
    Tjønneland, Anne
    Munk, Christian
    Pala, Valeria
    Palli, Domenico
    Khaw, Kay-Tee
    Barnabas, Ruanne V
    Overvad, Kim
    Clavel-Chapelon, Françoise
    Boutron-Ruault, Marie-Christine
    Fagherazzi, Guy
    Kaaks, Rudolf
    Lukanova, Annekatrin
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Steffen, Annika
    Trichopoulou, Antonia
    Trichopoulos, Dimitrios
    Klinaki, Eleni
    Tumino, Rosario
    Sacerdote, Carlotta
    Mattiello, Amalia
    Bueno-de-Mesquita, H Bas
    Peeters, Petra H
    Lund, Eiliv
    Weiderpass, Elisabete
    Quirós, J Ramón
    Sánchez, María-José
    Navarro, Carmen
    Barricarte, Aurelio
    Larrañaga, Nerea
    Ekström, Johanna
    Hortlund, Maria
    Lindquist, David
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Wareham, Nick
    Travis, Ruth C
    Rinaldi, Sabina
    Tommasino, Massimo
    Franceschi, Silvia
    Riboli, Elio
    Prospective seroepidemiologic study on the role of Human Papillomavirus and other infections in cervical carcinogenesis: Evidence from the EPIC cohort2014In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 135, no 2, p. 440-452Article in journal (Refereed)
    Abstract [en]

    To evaluate prospectively the association between serological markers of selected infections, including HPV, and risk of developing cervical cancer (CC) and pre-cancer, we performed a nested case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC) study that included 184 cases of invasive CC (ICC), 425 cases of cervical intraepithelial neoplasia (CIN) grade 3 or carcinoma in situ (CIS), and 1,218 matched control women. At enrollment participants completed lifestyle questionnaires and provided sera. Subjects were followed-up for a median of 9 years. Immunoassays were used to detect serum antibodies to Human Herpes Virus 2 (HHV-2), Chlamydia trachomatis (CT), Chlamydia pneumoniae, L1 proteins of mucosal and cutaneous HPV types, E6/E7 proteins of HPV16/18, as well as to four polyomaviruses. Adjusted odds ratios (OR) (and 95% confidence intervals (CI)) for CIN3/CIS and ICC risk were, respectively: 1.6 (1.2-2.0) and 1.8 (1.1-2.7) for L1 seropositivity to any mucosal HPV type, 1.0 (0.4-2.4) and 7.4 (2.8-19.7) for E6 seropositivity to HPV16/18, 1.3 (0.9-1.9) and 2.3 (1.3-4.1) for CT seropositivity, and 1.4 (1.0-2.0) and 1.5 (0.9-2.6) for HHV-2 seropositivity. The highest OR for ICC was observed for HPV16 E6 seropositivity (OR=10.2 (3.3-31.1)). Increasing number of sexually transmitted infections (STIs) was associated with increasing risk. Non-STIs were not associated with CC risk. In conclusion, this large prospective study confirms the important role of HPV and a possible contribution of CT and HHV-2 in cervical carcinogenesis. It further identifies HPV16 E6 seropositivity as the strongest marker to predict ICC well before disease development.

  • 24. Castro, Felipe A
    et al.
    Haimila, Katri
    Sareneva, Inna
    Schmitt, Markus
    Lorenzo, Justo
    Kunkel, Nelli
    Kumar, Rajiv
    Försti, Asta
    Kjellberg, Lennart
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Lehtinen, Matti
    Hemminki, Kari
    Pawlita, Michael
    Association of HLA-DRB1, interleukin-6 and cyclin D1 polymorphisms with cervical cancer in the Swedish population-A candidate gene approach.2009In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 125, no 8, p. 1851-1858Article in journal (Refereed)
    Abstract [en]

    High-risk human papillomavirus (hrHPV) infection is the major risk factor for cervical cancer (CxCa). The role of genetic susceptibility in the disease has been suggested, but the existing data lack consistency. We conducted a nested case-control study on 973 CxCa cases and 1,763 matched controls, from two Swedish population-based cohorts to examine the association of common genetic variants with CxCa risk. Human leukocyte antigen (HLA) alleles and 24 other polymorphisms in 14 genes were selected on the basis of reported association or mechanistic plausibility with an HPV infection or cervical cancer development. Genotyping was conducted using multiplex PCR and Luminex technology. A significant association of CxCa with various polymorphisms was observed: rs1800797 in the IL-6 gene (odds ratio [OR] = 0.88, 95% confidence intervals [CI]: 0.79-0.99); rs1041981 in the LTA gene (OR = 0.87, 95% CI: 0.78-0.98), and rs9344 in the CCND1 gene (OR = 1.14, 95% CI: 1.02-1.27), for those individuals carrying the rare allele. Additionally, the alleles 0401 and 1501 of the HLA class II DRB1 locus were associated with an increased risk (OR = 1.23, 95% CI: 1.04-1.45 and OR = 1.29, 95% CI: 1.11-1.50, respectively), and allele 1301 was associated with decreased risk (OR = 0.59, 95% CI: 0.47-0.73). The effects of CCND1 and the HLA*DRB1 alleles were independent of the effect of smoking. We did not find any association of risk with polymorphisms in genes related to the innate immune system. In conclusion, our study provides evidence for genetic susceptibility to CxCa due to variations in genes involved in the immune system and in cell cycle. (c) 2009 UICC.

  • 25. Castro, Felipe A.
    et al.
    Ivansson, Emma L.
    Schmitt, Markus
    Juko-Pecirep, Ivana
    Kjellberg, Lennart
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Hildesheim, Allan
    Gyllensten, Ulf B.
    Pawlita, Michael
    Contribution of TMC6 and TMC8 (EVER1 and EVER2) variants to cervical cancer susceptibility2012In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 130, no 2, p. 349-355Article in journal (Refereed)
    Abstract [en]

    Cervical cancer (CxCa) is caused by persistent human papillomavirus (HPV) infection; genetic predisposition is also suspected to play a role. Our study is a targeted candidate gene follow-up based on: (i) strong clinical evidence demonstrating that mutations in the TMC6 and TMC8 (EVER1 and EVER2) genes associate with the HPV-associated disease epidermodysplasia verruciformis (EV) and (ii) recent epidemiological data suggesting a genetic susceptibility conferred by polymorphisms in such genes for skin and CxCa. Clarifying the association of the TMC6/8 genes with risk of CxCa will help in understanding why some HPV-infected women develop persistent infection, cervical lesions and eventually cancer while others do not. Twenty-two single nucleotide polymorphisms (SNPs) harboring the TMC6/8 genes were genotyped in 2,989 cases with cervical intraepithelial neoplasia grade III or invasive CxCa and 2,281 controls from the Swedish population. Association was evaluated in logistic regression models. Two SNPs displayed association with cervical disease: rs2290907 [odds ratio (OR)GGvsAA = 0.6, 95% confidence interval (95% CI): 0.30.9, p = 0.02)] and rs16970849 (ORAGvsGG = 0.8, 95% CI: 0.660.98, p = 0.03). The present data support the involvement of the TMC6/8 region in CxCa susceptibility but further analyses are needed to replicate our findings, fully characterize the region and understand the function of the genetic variants involved.

  • 26.
    Cederquist, Kristina
    et al.
    Umeå University, Faculty of Medicine, Medical Biosciences, Medical and Clinical Genetics.
    Emanuelsson, Monica
    Umeå University, Faculty of Medicine, Radiation Sciences, Oncology.
    Göransson, Ingela
    Umeå University, Faculty of Medicine, Radiation Sciences, Oncology.
    Holinski-Feder, Elke
    Müller-Koch, Yvonne
    Golovleva, Irina
    Umeå University, Faculty of Medicine, Medical Biosciences, Medical and Clinical Genetics.
    Grönberg, Henrik
    Umeå University, Faculty of Medicine, Radiation Sciences, Oncology.
    Mutation analysis of the MLH1, MSH2 and MSH6 genes in patients with double primary cancers of the colorectum and the endometrium: a population-based study in northern Sweden2004In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 109, no 3, p. 370-376Article in journal (Refereed)
    Abstract [en]

    Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal dominant disorder that predisposes to predominantly colorectal and endometrial cancers due to germline mutations in DNA mismatch repair genes, mainly MLH1, MSH2 and in families with excess endometrial cancer also MSH6. In this population-based study, we analysed the mutation spectrum of the MLH1, MSH2 and MSH6 genes in a cohort of patients with microsatellite unstable double primary tumours of the colorectum and the endometrium by PCR, DHPLC and sequencing. Fourteen of the 23 patients (61%) had sequence variants in MLH1, MSH2 or MSH6 that likely affect the protein function. A majority (10/14) of the mutations was found among probands diagnosed before age 50. Five of the mutations (36%) were located in MLH1, 3 (21%) in MSH2 and 6 (43%) in MSH6. MSH6 seem to have larger impact in our population than in other populations, due to a founder effect since all of the MSH6 families originate from the same geographical area. MSH6 mutation carriers have later age of onset of both colorectal cancer (62 vs. 51 years) and endometrial cancer (58 vs. 48 years) and a larger proportion of endometrial cancer than MLH1 or MSH2 mutation carriers. We can conclude that patients with microsatellite unstable double primary cancers of the colorectum and the endometrium have a very high risk of carrying a mutation not only in MLH1 or MSH2 but also in MSH6, especially if they get their first cancer diagnosis before the age of 50. Copyright 2004 Wiley-Liss, Inc.

  • 27.
    Cederquist, Kristina
    et al.
    Umeå University, Faculty of Medicine, Medical Biosciences.
    Golovleva, Irina
    Umeå University, Faculty of Medicine, Medical Biosciences.
    Emanuelsson, Monica
    Umeå University, Faculty of Medicine, Radiation Sciences, Oncology.
    Stenling, Roger
    Umeå University, Faculty of Medicine, Medical Biosciences, Pathology.
    Grönberg, Henrik
    Umeå University, Faculty of Medicine, Radiation Sciences, Oncology.
    A population based cohort study of patients with multiple colon and endometrial cancer: correlation of microsatellite instability (MSI) staus, age at diagnosis and cancer risk2001In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 91, no 4, p. 486-491Article in journal (Refereed)
    Abstract [en]

    Hereditary non-polyposis colorectal cancer, HNPCC, is an autosomal dominant condition predisposing to cancers of primarily the colorectum and the endometrium. The aim of our study was to identify persons at a high risk of hereditary colorectal cancer and to estimate their risk of colon and other HNPCC-associated tumours. Family histories of cancer were obtained on 89 persons with double primary (DP) cancers of the colon and the endometrium. The cancer risks in their 649 first-degree-relatives (FDR) were analysed. The microsatellite instability (MSI) status of the tumour of the proband was also analysed and the cancer risks were estimated in relation to MSI status and age at diagnosis in the proband (over or under 50 years). The overall standardised incidence ratio (SIR) was 1.69 (95% CI; 1.39-2.03). In the =50-year-old cohort the SIR was 2.67 (95% CI; 2.08-3.38). Colon, rectal and uterus cancer exhibited significantly increased risks. This risk was further increased in the =50-year-old MSI positive families. Several =50-year-old MSI negative HNPCC-like families with increased risks were also identified. In conclusion a FDR to a person with a DP cancer of the colorectum or the colon/endometrium have a significantly increased risk of having a colorectal or other HNPCC-associated cancers if the proband is diagnosed with one of the cancers before age 50. These families are candidates for genetic counselling and colorectal screening programmes. Mutations in mismatch repair genes can explain some of the increased risk in these families, but mutations in MSI negative families are probably due to other colon cancer susceptibility genes not yet described. Copyright 2001 Wiley-Liss, Inc.

  • 28. Cervenka, Iris
    et al.
    Al Rahmoun, Marie
    Mahamat-Saleh, Yahya
    Fournier, Agnes
    Boutron-Ruault, Marie-Christine
    Severi, Gianluca
    Caini, Saverio
    Palli, Domenico
    Ghiasvand, Reza
    Veierod, Marit B.
    Botteri, Edoardo
    Tjonneland, Anne
    Olsen, Anja
    Fortner, Renee T.
    Kaaks, Rudolf
    Schulze, Matthias B.
    Panico, Salvatore
    Trichopoulou, Antonia
    Dessinioti, Clio
    Niforou, Katerina
    Sieri, Sabina
    Tumino, Rosario
    Sacerdote, Carlotta
    Bueno-de-Mesquita, Bas
    Sandanger, Torkjel M.
    Colorado-Yohar, Sandra
    Sanchez, Maria J.
    Gil Majuelo, Leire
    Lujan-Barroso, Leila
    Ardanaz, Eva
    Merino, Susana
    Isaksson, Karolin
    Butt, Salma
    Ljuslinder, Ingrid
    Jansson, Malin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Travis, Ruth C.
    Khaw, Kay-Tee
    Weiderpass, Elisabete
    Dossus, Laure
    Rinaldi, Sabina
    Kvaskoff, Marina
    Exogenous hormone use and cutaneous melanoma risk in women: The European Prospective Investigation into Cancer and Nutrition2020In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 146, no 12, p. 3267-3280Article in journal (Refereed)
    Abstract [en]

    Evidence suggests an influence of sex hormones on cutaneous melanoma risk, but epidemiologic findings are conflicting. We examined the associations between use of oral contraceptives (OCs) and menopausal hormone therapy (MHT) and melanoma risk in women participating in the European Prospective Investigation into Cancer and Nutrition (EPIC). EPIC is a prospective cohort study initiated in 1992 in 10 European countries. Information on exogenous hormone use at baseline was derived from country‐specific self‐administered questionnaires. We used Cox proportional hazards regression models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). Over 1992–2015, 1,696 melanoma cases were identified among 334,483 women, whereof 770 cases among 134,758 postmenopausal women. There was a positive, borderline‐significant association between OC use and melanoma risk (HR = 1.12, 95% CI = 1.00–1.26), with no detected heterogeneity across countries (phomogeneity = 0.42). This risk increased linearly with duration of use (ptrend = 0.01). Among postmenopausal women, ever use of MHT was associated with a nonsignificant increase in melanoma risk overall (HR = 1.14, 95% CI = 0.97–1.43), which was heterogeneous across countries (phomogeneity = 0.05). Our findings do not support a strong and direct association between exogenous hormone use and melanoma risk. In order to better understand these relations, further research should be performed using prospectively collected data including detailed information on types of hormone, and on sun exposure, which may act as an important confounder or effect modifier on these relations.

  • 29. 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 University, Faculty of Medicine, Department of Biobank Research. Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
    Harlid, Sophia
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    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 Nutrition2020In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 146, no 10, p. 2680-2693Article in journal (Refereed)
    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.

  • 30. 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 University, Faculty of Medicine, Department of Biobank Research. Department of Surgical Science, Uppsala University, Uppsala, Sweden.
    Harlid, Sophia
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    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) cohort2021In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 148, no 7, p. 1637-1651Article in journal (Refereed)
    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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  • 31. Companioni, Osmel
    et al.
    Bonet, Catalina
    Muñoz, Xavier
    Weiderpass, Elisabete
    Panico, Salvatore
    Tumino, Rosario
    Palli, Domenico
    Agnoli, Claudia
    Vineis, Paolo
    Boutron-Ruault, Marie-Christine
    Racine, Antoine
    Clavel-Chapelon, Françoise
    Travis, Ruth C
    Khaw, Kay-Tee
    Riboli, Elio
    Murphy, Neil
    Vergnaud, Anne-Claire
    Trichopoulou, Antonia
    Benetou, Vassiliki
    Trichopoulos, Dimitrios
    Lund, Eiliv
    Johansen, Dorthe
    Lindkvist, Björn
    Johansson, Mattias
    Umeå University, Faculty of Medicine, Department of Biobank Research. International Agency for Research on Cancer (IARC-WHO), Lyon, France.
    Sund, Malin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Ardanaz, Eva
    Sánchez-Cantalejo, Emilio
    Huerta, Jose M
    Dorronsoro, Miren
    Quirós, José Ramón
    Tjonneland, Anne
    Mortensen, Lotte Maxild
    Overvad, Kim
    Chang-Claude, Jenny
    Rizzato, Cosmeri
    Boeing, Heiner
    de Mesquita, H Bas Bueno
    Siersema, Peter
    Peeters, Petra Hm
    Numans, Mattijs E
    Carneiro, Fatima
    Licaj, Idlir
    Freisling, Heinz
    Sala, Núria
    González, Carlos A
    Polymorphisms of H. pylori signaling pathway genes and gastric cancer risk in the European EPIC-eurgast cohort2014In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 134, no 1, p. 92-101Article in journal (Refereed)
    Abstract [en]

    Helicobacter pylori is a recognized causal factor of noncardia gastric cancer (GC). Lipopolysaccaride and peptidoglycan of this bacterium are recognized by CD14, TLR4 and NOD2 human proteins, while NFKB1 activates the transcription of pro-inflammatory cytokines to elicit an immune response. SNPs in these genes have been associated with GC in different populations. We genotyped 30 SNPs of these genes, in 365 gastric adenocarcinomas and 1284 matched controls from the EPIC cohort. The association with GC and its histological and anatomical subtypes was analyzed by logistic regression and corrected for multiple comparisons. Using a log-additive model we found a significant association between SNPs in CD14, NOD2 and TLR4 with GC risk. However, after applying the multiple comparisons tests only the NOD2 region remained significant (p=0.009). Analysis according to anatomical subtypes revealed NOD2 and NFKB1 SNPs associated with noncardia GC and CD14 SNPs associated with cardia GC, while analysis according to histological subtypes showed that CD14 was associated with intestinal but not diffuse GC. The multiple comparisons tests confirmed the association of NOD2 with noncardia GC (p=0.0003) and CD14 with cardia GC (p=0.01). Haplotype analysis was in agreement with single SNP results for NOD2 and CD14 genes. From these results we conclude that genetic variation in NOD2 associates with noncardia GC while variation in CD14 is associated with cardia GC.

  • 32. Crawley, Danielle
    et al.
    Garmo, Hans
    Rudman, Sarah
    Stattin, Pär
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology. Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
    Häggström, Christel
    Umeå University, Faculty of Medicine, Department of Biobank Research. Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology. Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
    Zethelius, Björn
    Holmberg, Lars
    Adolfsson, Jan
    Van Hemelrijck, Mieke
    Association between duration and type of androgen deprivation therapy and risk of diabetes in men with prostate cancer2016In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 139, no 12, p. 2698-2704Article in journal (Refereed)
    Abstract [en]

    Androgen deprivation therapy (ADT) for prostate cancer (PCa) increases risk of type 2 diabetes (T2DM); however the association between types and duration of ADT has not been fully elucidated. We examined how type and duration of ADT affects risk of T2DM. Using data from Prostate Cancer database Sweden (PCBaSe) we investigated risk of T2DM in a cohort of 34,031 men with PCa on ADT; i.e., anti-androgens (AA), orchiectomy, or gonadotropin-releasing hormone (GnRH) agonists compared to an age-matched, PCa-free comparison cohort (n = 167,205) using multivariate Cox proportional hazard regression. T2DM was defined as a newly filled prescription for metformin, sulphonylurea, or insulin in the Prescribed Drug Register. A total of 21,874 men with PCa received GnRH agonists, 9,143 AA and 3,014 underwent orchiectomy. Risk of T2DM was increased in men in the GnRH agonists/orchiectomy group during the first 3 years of ADT [i.e., 1 - 1.5 years HR: 1.61 (95%CI: 1.36 - 1.91)], compared to PCa-free men. The risk decreased thereafter (e.g., 3 - 4 years HR: 1.17 (95% CI: 0.98 - 1.40)). Conversely, no increased risk was seen in men on AA (HR: 0.74 (95%CI: 0.65 - 0.84). The incidence of T2DM per 1,000 person-years was 10 for PCa-free men, 8 for men on AA, and 13 for men on GnRH agonists/orchiectomy. Duration of ADT has a significant impact on risk of T2DM. With the peak after three years of treatment, our data indicates that men on ADT, even for a limited period of time, such as adjuvant to radiotherapy, are at increased risk of T2DM.

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  • 33. Dahlgren, Liselotte
    et al.
    Dahlstrand, Hanna Mellin
    Lindquist, David
    Karolinska Instituet, Institutionen för Onkologi-Patologi.
    Högmo, Anders
    Björnestål, Linda
    Lindholm, Johan
    Lundberg, Bertil
    Dalianis, Tina
    Munck-Wikland, Eva
    Human papillomavirus is more common in base of tongue than in mobile tongue cancer and is a favorable prognostic factor in base of tongue cancer patients.2004In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 112, no 6, p. 1015-9Article in journal (Refereed)
    Abstract [en]

    The frequency of human papilloma virus (HPV) and its influence on clinical outcome was analyzed retrospectively in pre-treatment paraffin embedded biopsies from 110 patients with tongue cancer. The presence of HPV DNA was examined in 85 mobile tongue tumors and 25 base of tongue tumors by a polymerase chain reaction (PCR) with 2 general primer pairs, GP5+/6+ and CPI/IIG. When HPV-DNA was found, HPV-type specific primers and direct sequencing were used for HPV sub-type verification. Twelve of 110 (10.9%) samples were HPV-positive; 9 for HPV-16, 1 for HPV-33, 1 for HPV-35 and 1 could not be analyzed because of shortage of DNA. HPV was significantly more common in base of tongue tumors (10/25, 40.0%) compared to tumors of the mobile tongue (2/85, 2.3%). The influence of HPV on clinical outcome in mobile tongue cancer could not be studied, due to that HPV was present in too few cases. Of the 19 patients with base of tongue cancer that were included in the survival analysis, however, 7 patients with HPV-positive base of tongue cancer had a significantly favorable 5-year survival rate compared to the 12 HPV-negative patients. In conclusion, HPV is significantly more common in base of tongue cancer than in mobile tongue cancer, and has a positive impact on disease-specific survival in patients with base of tongue cancer.

  • 34.
    Dahlin, Anna M
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Van Guelpen, Bethany
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Hultdin, Johan
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology, Cariology.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Palmqvist, Richard
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Plasma vitamin B12 concentrations and the risk of colorectal cancer: a nested case-referent study2008In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 32, no 2, p. 304-314Article in journal (Refereed)
    Abstract [en]

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

  • 35. Dai, Juncheng
    et al.
    Huang, Mingtao
    Amos, Christopher I.
    Hung, Rayjean J.
    Tardon, Adonina
    Andrew, Angeline
    Chen, Chu
    Christiani, David C.
    Albanes, Demetrius
    Rennert, Gadi
    Fan, Jingyi
    Goodman, Gary
    Liu, Geoffrey
    Field, John K.
    Grankvist, Kjell
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Kiemeney, Lambertus A.
    Le Marchand, Loic
    Schabath, Matthew B.
    Johansson, Mattias
    Aldrich, Melinda C.
    Johansson, Mikael
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Caporaso, Neil
    Lazarus, Philip
    Lam, Stephan
    Bojesen, Stig E.
    Arnold, Susanne
    Landi, Maria Teresa
    Risch, Angela
    Wichmann, H-Erich
    Bickeboller, Heike
    Brennan, Paul
    Shete, Sanjay
    Melander, Olle
    Brunnstrom, Hans
    Zienolddiny, Shan
    Woll, Penella
    Stevens, Victoria
    Hu, Zhibin
    Shen, Hongbing
    Genome-wide association study of INDELs identified four novel susceptibility loci associated with lung cancer risk2020In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 146, no 10, p. 2855-2864Article in journal (Refereed)
    Abstract [en]

    Genome-wide association studies (GWAS) have identified 45 susceptibility loci associated with lung ncer. Only less than SNPs, small insertions and deletions (INDELs) are the second most abundant netic polymorphisms in the human genome. INDELs are highly associated with multiple human seases, including lung cancer. However, limited studies with large-scale samples have been available to stematically evaluate the effects of INDELs on lung cancer risk. Here, we performed a large-scale meta- alysis to evaluate INDELs and their risk for lung cancer in 23,202 cases and 19,048 controls. Functional notations were performed to further explore the potential function of lung cancer risk INDELs. nditional analysis was used to clarify the relationship between INDELs and SNPs. Four new risk loci re identified in genome-wide INDEL analysis (1p13.2: rs5777156, Insertion, OR = 0.92, p = 9.10 x 10(- ; 4q28.2: rs58404727, Deletion, OR = 1.19, p = 5.25 x 10(-7); 12p13.31: rs71450133, Deletion, OR = 09, p = 8.83 x 10(-7); and 14q22.3: rs34057993, Deletion, OR = 0.90, p = 7.64 x 10(-8)). The eQTL alysis and functional annotation suggested that INDELs might affect lung cancer susceptibility by gulating the expression of target genes. After conducting conditional analysis on potential causal SNPs, e INDELs in the new loci were still nominally significant. Our findings indicate that INDELs could be tentially functional genetic variants for lung cancer risk. Further functional experiments are needed to tter understand INDEL mechanisms in carcinogenesis.

  • 36. Dik, Vincent K
    et al.
    Bueno-de-Mesquita, H Bas
    Van Oijen, Martijn GH
    Siersema, Peter D
    Uiterwaal, Cuno SPM
    Van Gils, Carla H
    Van Duijnhoven, Fränzel JB
    Cauchi, Stéphane
    Yengo, Loic
    Froguel, Philippe
    Overvad, Kim
    Bech, Bodil H
    Tjønneland, Anne
    Olsen, Anja
    Boutron-Ruault, Marie-Christine
    Racine, Antoine
    Fagherazzi, Guy
    Kühn, Tilman
    Campa, Daniele
    Boeing, Heiner
    Aleksandrova, Krasimira
    Trichopoulou, Antonia
    Peppa, Eleni
    Oikonomou, Eleni
    Palli, Domenico
    Grioni, Sara
    Vineis, Paolo
    Tumino, Rosaria
    Panico, Salvatore
    Peeters, Petra HM
    Weiderpass, Elisabete
    Engeset, Dagrun
    Braaten, Tonje
    Dorronsoro, Miren
    Chirlaque, María-Dolores
    Sánchez, María-José
    Barricarte, Aurelio
    Zamora-Ros, Raul
    Argüelles, Marcial
    Jirström, Karin
    Wallström, Peter
    Nilsson, Lena Maria
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research. Umeå University, Arctic Research Centre at Umeå University.
    Ljuslinder, Ingrid
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology. Umeå University, Arctic Research Centre at Umeå University.
    Travis, Ruth C
    Khaw, Kay-Tee
    Wareham, Nick
    Freisling, Heinz
    Licaj, Idlir
    Jenab, Mazda
    Gunter, Marc J
    Murphy, Neil
    Romaguera-Bosch, Dora
    Riboli, Elio
    Coffee and tea consumption, genotype based CYP1A2 and NAT2 activity, and colorectal cancer risk: results from the EPIC cohort study2014In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 135, no 2, p. 401-412Article in journal (Refereed)
    Abstract [en]

    Coffee and tea contain numerous antimutagenic and antioxidant components and high levels of caffeine that may protect against colorectal cancer (CRC). We investigated the association between coffee and tea consumption and CRC risk and studied potential effect modification by CYP1A2 and NAT2 genotypes, enzymes involved in the metabolization of caffeine. Data from 477,071 participants (70.2% female) of the European Investigation into Cancer and Nutrition (EPIC) cohort study were analyzed. At baseline (1992-2000) habitual (total, caffeinated and decaffeinated) coffee and tea consumption was assessed with dietary questionnaires. Cox proportional hazards models were used to estimate adjusted hazard ratio's (HR) and 95%-confidence intervals (95%-CI). Potential effect modification by genotype-based CYP1A2 and NAT2 activity was studied in a nested case-control set of 1,252 cases and 2,175 controls. After a median follow-up of 11.6 years, 4,234 participants developed CRC (mean age 64.7±8.3 years). Total coffee consumption (high vs. non/low) was not associated with CRC risk (HR 1.06, 95%-CI 0.95-1.18) or subsite cancers, and no significant associations were found for caffeinated (HR 1.10, 95%-CI 0.97-1.26) and decaffeinated coffee (HR 0.96, 95%-CI 0.84-1.11) and tea (HR 0.97, 95%-CI 0.86-1.09). High coffee and tea consuming subjects with slow CYP1A2 or NAT2 activity had a similar CRC risk compared to non/low coffee and tea consuming subjects with a fast CYP1A2 or NAT2 activity, which suggest that caffeine metabolism does not affect the link between coffee and tea consumption and CRC risk. This study shows that coffee and tea consumption is not likely to be associated with overall CRC.

  • 37. Dossus, Laure
    et al.
    Allen, Naomi
    Kaaks, Rudolf
    Bakken, Kjersti
    Lund, Eiliv
    Tjonneland, Anne
    Olsen, Anja
    Overvad, Kim
    Clavel-Chapelon, Francoise
    Fournier, Agnes
    Chabbert-Buffet, Nathalie
    Boeing, Heiner
    Schütze, Madlen
    Trichopoulou, Antonia
    Trichopoulos, Dimitrios
    Lagiou, Pagona
    Palli, Domenico
    Krogh, Vittorio
    Tumino, Rosario
    Vineis, Paolo
    Mattiello, Amalia
    Bueno-de-Mesquita, H Bas
    Onland-Moret, N Charlotte
    Peeters, Petra H M
    Dumeaux, Vanessa
    Redondo, Maria-Luisa
    Duell, Eric
    Sanchez-Cantalejo, Emilio
    Arriola, Larraitz
    Chirlaque, Maria-Dolores
    Ardanaz, Eva
    Manjer, Jonas
    Borgquist, Signe
    Lukanova, Annie
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Lundin, Eva
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Khaw, Kay-Tee
    Wareham, Nicholas
    Key, Tim
    Chajes, Veronique
    Rinaldi, Sabina
    Slimani, Nadia
    Mouw, Traci
    Gallo, Valentina
    Riboli, Elio
    Reproductive risk factors and endometrial cancer: the European prospective investigation into cancer and nutrition2010In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 127, no 2, p. 442-451Article in journal (Refereed)
    Abstract [en]

    Endometrial cancer risk has been associated with reproductive factors (age at menarche, age at menopause, parity, age at first and last birth, time since last birth and use of oral contraceptives (OCs)]. However, these factors are closely interrelated and whether they act independently still requires clarification. We conducted a study to examine the association of menstrual and reproductive variables with the risk of endometrial cancer among the European Prospective Investigation into Cancer and Nutrition (EPIC). Among the 302,618 women eligible for the study, 1,017 incident endometrial cancer cases were identified. A reduction in endometrial cancer risk was observed in women with late menarche, early menopause, past OC use, high parity and a shorter time since last full-term pregnancy (FTP). No association was observed for duration of breast feeding after adjustment for number of FTP or for abortion (spontaneous or induced). After mutual adjustment, late age at menarche, early age at menopause and duration of OC use showed similar risk reductions of 7-8% per year of menstrual life, whereas the decreased risk associated with cumulative duration of FTPs was stronger (22% per year). In conclusion, our findings confirmed a reduction in risk of endometrial cancer with factors associated with a lower cumulative exposure to estrogen and/or higher exposure to progesterone, such as increasing number of FTPs and shorter menstrual lifespan and, therefore, support an important role of hormonal mechanisms in endometrial carcinogenesis.

  • 38.
    Dossus, Laure
    et al.
    Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
    Becker, Susen
    Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
    Rinaldi, Sabina
    Section of Nutrition and Metabolism, International Agency for Research on Cancer, Lyon, France.
    Lukanova, Annekatrin
    Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
    Tjønneland, Anne
    Institute of Cancer Epidemiology, Danish Cancer Society, Copenhagen, Denmark.
    Olsen, Anja
    Institute of Cancer Epidemiology, Danish Cancer Society, Copenhagen, Denmark.
    Overvad, Kim
    Department of Epidemiology, School of Public Health, Aarhus University, Aarhus, Denmark.
    Chabbert-Buffet, Nathalie
    Department of Obstetrics and Gynecology, APHP Hospital Tenon and UMPC, Paris, France.
    Boutron-Ruault, Marie-Christine
    INSERM, Centre for Research in Epidemiology and Population Health, Paris South University, Gustave Roussy Institute, Villejuif, France.
    Clavel-Chapelon, Françoise
    INSERM, Centre for Research in Epidemiology and Population Health, Paris South University, Gustave Roussy Institute, Villejuif, France.
    Teucher, Birgit
    Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
    Chang-Claude, Jenny
    Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
    Pischon, Tobias
    Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany.
    Boeing, Heiner
    Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany.
    Trichopoulou, Antonia
    Department of Hygiene, Epidemiology and Medical Statistics, WHO Collaborating Center for Food and Nutrition Policies, University of Athens Medical School, Athens, Greece.
    Benetou, Vasiliki
    Department of Hygiene, Epidemiology and Medical Statistics, WHO Collaborating Center for Food and Nutrition Policies, University of Athens Medical School, Athens, Greece.
    Valanou, Elisavet
    Department of Hygiene, Epidemiology and Medical Statistics, WHO Collaborating Center for Food and Nutrition Policies, University of Athens Medical School, Athens, Greece.
    Palli, Domenico
    Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute (ISPO), Florence, Italy.
    Sieri, Sabina
    Department of Preventive and Predictive Medicine, Nutritional Epidemiology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
    Tumino, Rosario
    Cancer Registry and Histopathology Unit, “Civile – M.P. Arezzo” Hospital, Ragusa, Italy.
    Sacerdote, Carlotta
    Center for Cancer Prevention (CPO Piedmont), Turin, Italy.
    Galasso, Rocco
    Instituto di Ricovero e Cura a Carattere Scientifico (IRCCS-CROOB), Rionero in Vulture (PZ), Italy.
    Redondo, Maria-Luísa
    Public Health and Participation Directorate, Health and Health Care Services Council, Asturias, Spain.
    Bonet Bonet, Catalina
    Unit of Nutrition, Environment and Cancer, Cancer Epidemiology Research Programme, Catalan Institute of Oncology (ICO), Barcelona, Spain.
    Molina-Montes, Esther
    Andalusian School of Public Health, Granada, Spain.
    Altzibar, Jone M
    CIBER de Epidemiología y Salud Pública (CIBERESP), Spain.
    Chirlaque, Maria-Dolores
    CIBER de Epidemiología y Salud Pública (CIBERESP), Spain.
    Ardanaz, Eva
    CIBER de Epidemiología y Salud Pública (CIBERESP), Spain.
    Bueno-de-Mesquita, H Bas
    CIBER de Epidemiología y Salud Pública (CIBERESP), Spain.
    van Duijnhoven, Fränzel J B
    National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands.
    Peeters, Petra H M
    Julius Center for Health Sciences and Primary Care, University Medical Center, Utrecht, The Netherlands.
    Onland-Moret, N Charlotte
    Julius Center for Health Sciences and Primary Care, University Medical Center, Utrecht, The Netherlands.
    Lundin, Eva
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Idahl, Annika
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Khaw, Kay-Tee
    Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom.
    Wareham, Nicholas
    MRC Epidemiology Unit, Cambridge, United Kingdom.
    Allen, Naomi
    Nuffield Department of Clinical Medicine, Cancer Epidemiology Unit, University of Oxford, Oxford, United Kingdom.
    Romieu, Isabelle
    International Agency for Research on Cancer, Lyon, France.
    Fedirko, Veronika
    International Agency for Research on Cancer, Lyon, France.
    Hainaut, Pierre
    Department of Epidemiology and Biostatistics, School of Public Health, Imperial College, London, United Kingdom.
    Romaguera, Dora
    Department of Epidemiology and Biostatistics, School of Public Health, Imperial College, London, United Kingdom.
    Norat, Teresa
    Department of Epidemiology and Biostatistics, School of Public Health, Imperial College, London, United Kingdom.
    Riboli, Elio
    Department of Epidemiology and Biostatistics, School of Public Health, Imperial College, London, United Kingdom.
    Kaaks, Rudolf
    Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
    Tumor necrosis factor (TNF)-α, soluble TNF receptors and endometrial cancer risk: the EPIC study2011In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 129, no 8, p. 2032-2037Article in journal (Refereed)
    Abstract [en]

    Chronic inflammation has been hypothesized to play a role in endometrial cancer development. Tumor necrosis factor-α (TNF-α), one of the major pro-inflammatory cytokines, has also been implicated in endometrial physiology. We conducted a case-control study nested within the European prospective investigation into cancer and nutrition (EPIC) to examine the association of TNF-α and its two soluble receptors (sTNFR1 and sTNFR2) with endometrial cancer risk. Two-hundred-seventy cases and 518 matched controls were analyzed using conditional logistic regression. All statistical tests were two-sided. We observed an increased risk of endometrial cancer among women in the highest versus lowest quartile of TNF-α (odds ratio [OR]: 1.73, 95% CI: 1.09-2.73, Ptrend = 0.01), sTNFR1 (OR: 1.68, 95% CI: 0.99-2.86, Ptrend = 0.07) and sTNFR2 (OR: 1.53, 95%CI: 0.92-2.55, Ptrend = 0.03) after adjustment for body-mass-index, parity, age at menopause and previous postmenopausal hormone therapy use. Further adjustments for estrogens and C-peptide had minor effect on risk estimates. Our data show that elevated prediagnostic concentrations of TNF-α and its soluble receptors are related to a higher risk of endometrial cancer, particularly strong in women diagnosed within 2 years of blood donation. This is the first study of its kind and therefore deserves replication in further prospective studies.

  • 39. Dossus, Laure
    et al.
    Franceschi, Silvia
    Biessy, Carine
    Navionis, Anne-Sophie
    Travis, Ruth C
    Weiderpass, Elisabete
    Scalbert, Augustin
    Romieu, Isabelle
    Tjønneland, Anne
    Olsen, Anja
    Overvad, Kim
    Boutron-Ruault, Marie-Christine
    Bonnet, Fabrice
    Fournier, Agnès
    Fortner, Renee T
    Kaaks, Rudolf
    Aleksandrova, Krasimira
    Trichopoulou, Antonia
    La Vecchia, Carlo
    Peppa, Eleni
    Tumino, Rosario
    Panico, Salvatore
    Palli, Domenico
    Agnoli, Claudia
    Vineis, Paolo
    Bueno-de-Mesquita, H B As
    Peeters, Petra H
    Skeie, Guri
    Zamora-Ros, Raul
    Chirlaque, María-Dolores
    Ardanaz, Eva
    Sánchez, Maria-Jose
    Ramón Quirós, Jose
    Dorronsoro, Miren
    Sandström, Maria
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Nilsson, Lena Maria
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Schmidt, Julie A
    Khaw, Kay-Tee
    Tsilidis, Konstantinos K
    Aune, Dagfinn
    Riboli, Elio
    Rinaldi, Sabina
    Adipokines and inflammation markers and risk of differentiated thyroid carcinoma: The EPIC study2018In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 142, no 7, p. 1332-1342Article in journal (Refereed)
    Abstract [en]

    Other than the influence of ionizing radiation and benign thyroid disease, little is known about the risk factors for differentiated thyroid cancer (TC) which is an increasing common cancer worldwide. Consistent evidence shows that body mass is positively associated with TC risk. As excess weight is a state of chronic inflammation, we investigated the relationship between concentrations of leptin, adiponectin, C-reactive protein, interleukin (IL)-6, IL-10 and tumor necrosis factor (TNF)-α and the risk of TC. A case-control study was nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) study and included 475 first primary incident TC cases (399 women and 76 men) and 1,016 matched cancer-free cohort participants. Biomarkers were measured in serum samples using validated and highly sensitive commercially available immunoassays. Odds ratios (ORs) of TC by levels of each biomarker were estimated using conditional logistic regression models, adjusting for BMI and alcohol consumption. Adiponectin was inversely associated with TC risk among women (ORT3vs.T1  = 0.69, 95% CI: 0.49-0.98, Ptrend  = 0.04) but not among men (ORT3vs.T1  = 1.36, 95% CI: 0.67-2.76, Ptrend  = 0.37). Increasing levels of IL-10 were positively associated with TC risk in both genders and significantly so in women (ORT3vs.T1  = 1.59, 95% CI: 1.13-2.25, Ptrend  = 0.01) but not in men (ORT3vs.T1  = 1.78, 95% CI: 0.80-3.98, Ptrend  = 0.17). Leptin, CRP, IL-6 and TNF-α were not associated with TC risk in either gender. These results indicate a positive association of TC risk with IL-10 and a negative association with adiponectin that is probably restricted to women. Inflammation may play a role in TC in combination with or independently of excess weight.

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  • 40. Duarte-Salles, Talita
    et al.
    Fedirko, Veronika
    Stepien, Magdalena
    Aleksandrova, Krasimira
    Bamia, Christina
    Lagiou, Pagona
    Laursen, Anne Sofie Dam
    Hansen, Louise
    Overvad, Kim
    Tjønneland, Anne
    Boutron-Ruault, Marie-Christine
    Fagherazzi, Guy
    His, Mathilde
    Boeing, Heiner
    Katzke, Verena
    Kühn, Tilman
    Trichopoulou, Antonia
    Valanou, Elissavet
    Kritikou, Maria
    Masala, Giovanna
    Panico, Salvatore
    Sieri, Sabina
    Ricceri, Fulvio
    Tumino, Rosario
    Bueno-de-Mesquita, H B As
    Peeters, Petra H
    Hjartåker, Anette
    Skeie, Guri
    Weiderpass, Elisabete
    Ardanaz, Eva
    Bonet, Catalina
    Chirlaque, Maria-Dolores
    Dorronsoro, Miren
    Quirós, J Ramón
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Ohlsson, Bodil
    Sjöberg, Klas
    Wennberg, Maria
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Khaw, Kay-Tee
    Travis, Ruth C
    Wareham, Nick
    Ferrari, Pietro
    Freisling, Heinz
    Romieu, Isabelle
    Cross, Amanda J
    Gunter, Marc
    Lu, Yunxia
    Jenab, Mazda
    Dietary fat, fat subtypes and hepatocellular carcinoma in a large European cohort2015In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 137, no 11, p. 2715-2728Article in journal (Refereed)
    Abstract [en]

    The role of amount and type of dietary fat consumption in the etiology of hepatocellular carcinoma (HCC) is poorly understood, despite suggestive biological plausibility. The associations of total fat, fat subtypes and fat sources with HCC incidence were investigated in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, which includes 191 incident HCC cases diagnosed between 1992 and 2010. Diet was assessed by country-specific, validated dietary questionnaires. A single 24-hr diet recall from a cohort subsample was used for measurement error calibration. Hazard ratios (HR) and 95% confidence intervals (95% CI) were estimated from Cox proportional hazard models. Hepatitis B and C viruses (HBV/HCV) status and biomarkers of liver function were assessed separately in a nested case-control subset with available blood samples (HCC = 122). In multivariable calibrated models, there was a statistically significant inverse association between total fat intake and risk of HCC (per 10 g/day, HR = 0.80, 95% CI: 0.65-0.99), which was mainly driven by monounsaturated fats (per 5 g/day, HR = 0.71, 95% CI: 0.55-0.92) rather than polyunsaturated fats (per 5 g/day, HR = 0.92, 95% CI: 0.68-1.25). There was no association between saturated fats (HR = 1.08, 95% CI: 0.88-1.34) and HCC risk. The ratio of polyunsaturated/monounsaturated fats to saturated fats was not significantly associated with HCC risk (per 0.2 point, HR = 0.86, 95% CI: 0.73-1.01). Restriction of analyses to HBV/HCV free participants or adjustment for liver function did not substantially alter the findings. In this large prospective European cohort, higher consumption of monounsaturated fats is associated with lower HCC risk.

  • 41. Duarte-Salles, Talita
    et al.
    Fedirko, Veronika
    Stepien, Magdalena
    Trichopoulou, Antonia
    Bamia, Christina
    Lagiou, Pagona
    Lukanova, Annekatrin
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Trepo, Elisabeth
    Overvad, Kim
    Tjønneland, Anne
    Halkjaer, Jytte
    Boutron-Ruault, Marie-Christine
    Racine, Antoine
    Cadeau, Claire
    Kühn, Tilman
    Aleksandrova, Krasimira
    Trichopoulos, Dimitrios
    Tsiotas, Konstantinos
    Boffetta, Paolo
    Palli, Domenico
    Pala, Valeria
    Tumino, Rosario
    Sacerdote, Carlotta
    Panico, Salvatore
    Bueno-de-Mesquita, H B as
    Dik, Vincent K
    Peeters, Petra H
    Weiderpass, Elisabete
    Torhild Gram, Inger
    Hjartåker, Anette
    Ramón Quirós, Jose
    Fonseca-Nunes, Ana
    Molina-Montes, Esther
    Dorronsoro, Miren
    Navarro Sanchez, Carmen
    Barricarte, Aurelio
    Lindkvist, Björn
    Sonestedt, Emily
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology.
    Wennberg, Maria
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Khaw, Kay-Tee
    Wareham, Nick
    Travis, Ruth C
    Romieu, Isabelle
    Riboli, Elio
    Jenab, Mazda
    Dairy products and risk of hepatocellular carcinoma: the European Prospective Investigation into Cancer and Nutrition2014In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 135, no 7, p. 1662-1672Article in journal (Refereed)
    Abstract [en]

    Intake of dairy products has been associated with risk of some cancers, but findings are often inconsistent and information on hepatocellular carcinoma (HCC) risk is limited, particularly from prospective settings. The aim of our study was to investigate the association between consumption of total and specific dairy products (milk/cheese/yogurt) and their components (calcium/vitamin D/fats/protein), with first incident HCC (N(cases) = 191) in the European Prospective Investigation into Cancer and Nutrition cohort, including a nested case-control subset (N(cases) = 122) with the assessment of hepatitis B virus/hepatitis C virus infections status, liver damage and circulating insulin-like growth factor (IGF)-I levels. For cohort analyses, multivariable-adjusted Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CI). For nested case-control analyses, conditional logistic regression was used to calculate odds ratios and 95% CI. A total of 477,206 participants were followed-up for an average of 11 years (person-years follow-up = 5,415,385). In the cohort study, a significant positive HCC risk association was observed for total dairy products (highest vs. lowest tertile, HR = 1.66, 95% CI: 1.13-2.43; p(trend) = 0.012), milk (HR = 1.51, 95% CI: 1.02-2.24; p(trend) = 0.049), and cheese (HR = 1.56, 95% CI: 1.02-2.38; p(trend) = 0.101), but not yogurt (HR = 0.94, 95% CI: 0.65-1.35). Dietary calcium, vitamin D, fat and protein from dairy sources were associated with increased HCC risk, whereas the same nutrients from nondairy sources showed inverse or null associations. In the nested case-control study, similar results were observed among hepatitis-free individuals. Results from this large prospective cohort study suggest that higher consumption of dairy products, particularly milk and cheese, may be associated with increased HCC risk. Validation of these findings in other populations is necessary. Potential biologic mechanisms require further exploration.

  • 42. Duell, Eric J
    et al.
    Bonet, Catalina
    Muñoz, Xavier
    Lujan-Barroso, Leila
    Weiderpass, Elisabete
    Boutron-Ruault, Marie-Christine
    Racine, Antoine
    Severi, Gianluca
    Canzian, Federico
    Rizzato, Cosmeri
    Boeing, Heiner
    Overvad, Kim
    Tjønneland, Anne
    Argüelles, Marcial
    Sánchez-Cantalejo, Emilio
    Chamosa, Saioa
    Huerta, José María
    Barricarte, Aurelio
    Khaw, Kay-Tee
    Wareham, Nick
    Travis, Rutch C
    Trichopoulou, Antonia
    Trichopoulos, Dimitrios
    Yiannakouris, Nikos
    Palli, Domenico
    Agnoli, Claudia
    Tumino, Rosario
    Naccarati, Alessio
    Panico, Salvatore
    Bueno-de-Mesquita, H B As
    Siersema, Peter D
    Peeters, Petra H M
    Ohlsson, Bodil
    Lindkvist, Björn
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Biobank Research. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Ye, Weimin
    Umeå University, Faculty of Medicine, Department of Biobank Research. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Johansson, Matthias
    Umeå University, Faculty of Medicine, Department of Biobank Research.
    Fenger, Claus
    Riboli, Elio
    Sala, Núria
    González, Carlos A
    Variation at ABO histo-blood group and FUT loci and diffuse and intestinal gastric cancer risk in a European population2015In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 136, no 4, p. 880-893Article in journal (Refereed)
    Abstract [en]

    ABO blood serotype A is known to be associated with risk of gastric cancer (GC), but little is known how ABO alleles and the fucosyltransferase (FUT) enzymes and genes which are involved in Lewis antigen formation [and in Helicobacter pylori (H. pylori) binding and pathogenicity] may be related to GC risk in a European population. The authors conducted an investigation of 32 variants at ABO and FUT1-7 loci and GC risk in a case-control study of 365 cases and 1,284 controls nested within the EPIC cohort (the EPIC-Eurgast study). Four variants (including rs505922) in ABO, and allelic blood group A (AO+AA, odds ratio = 1.84, 95%CI = 1.20-2.80) were associated with diffuse-type GC; however, conditional models with other ABO variants indicated that the associations were largely due to allelic blood group A. One variant in FUT5 was also associated with diffuse-type GC, and four variants (and haplotypes) in FUT2 (Se), FUT3 (Le) and FUT6 with intestinal-type GC. Further, one variant in ABO, two in FUT3 and two in FUT6 were associated with H. pylori infection status in controls, and two of these (in FUT3 and FUT6) were weakly associated with intestinal-type GC risk. None of the individual variants surpassed a Bonferroni corrected p-value cutoff of 0.0016; however, after a gene-based permutation test, two loci [FUT3(Le)/FUT5/FUT6 and FUT2(Se)] were significantly associated with diffuse- and intestinal-type GC, respectively. Replication and functional studies are therefore recommended to clarify the role of ABO and FUT alleles in H. pylori infection and subtype-specific gastric carcinogenesis.

  • 43. Duell, Eric J.
    et al.
    Travier, Noemie
    Lujan-Barroso, Leila
    Dossus, Laure
    Boutron-Ruault, Marie-Christine
    Clavel-Chapelon, Francoise
    Tumino, Rosario
    Masala, Giovanna
    Krogh, Vittorio
    Panico, Salvatore
    Ricceri, Fulvio
    Luisa Redondo, Maria
    Dorronsoro, Miren
    Molina-Montes, Esther
    Huerta, Jose M.
    Barricarte, Aurelio
    Khaw, Kay-Tee
    Wareham, Nick J.
    Allen, Naomi E.
    Travis, Ruth
    Siersema, Peter D.
    Peeters, Petra H. M.
    Trichopoulou, Antonia
    Fragogeorgi, Eirini
    Oikonomou, Eleni
    Boeing, Heiner
    Schuetze, Madlen
    Canzian, Federico
    Lukanova, Annekatrin
    Tjonneland, Anne
    Roswall, Nina
    Overvad, Kim
    Weiderpass, Elisabete
    Gram, Inger Torhild
    Lund, Eiliv
    Lindkvist, Bjorn
    Johansen, Dorthe
    Ye, Weimin
    Umeå University, Faculty of Medicine, Department of Biobank Research.
    Sund, Malin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Fedirko, Veronika
    Jenab, Mazda
    Michaud, Dominique S.
    Riboli, Elio
    Bueno-de-Mesquita, H. Bas
    Menstrual and reproductive factors in women, genetic variation in CYP17A1, and pancreatic cancer risk in the European prospective investigation into cancer and nutrition (EPIC) cohort2013In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 132, no 9, p. 2164-2175Article in journal (Refereed)
    Abstract [en]

    Menstrual and reproductive factors and exogenous hormone use have been investigated as pancreatic cancer risk factors in case-control and cohort studies, but results have been inconsistent. We conducted a prospective examination of menstrual and reproductive factors, exogenous hormone use and pancreatic cancer risk (based on 304 cases) in 328,610 women from the EPIC cohort. Then, in a case-control study nested within the EPIC cohort, we examined 12 single nucleotide polymorphisms (SNPs) in CYP17A1 (an essential gene in sex steroid metabolism) for association with pancreatic cancer in women and men (324 cases and 353 controls). Of all factors analyzed, only younger age at menarche (<12 vs. 13 years) was moderately associated with an increased risk of pancreatic cancer in the full cohort; however, this result was marginally significant (HR = 1.44; 95% CI = 0.992.10). CYP17A1 rs619824 was associated with HRT use (p value = 0.037) in control women; however, none of the SNPs alone, in combination, or as haplotypes were associated with pancreatic cancer risk. In conclusion, with the possible exception of an early age of menarche, none of the menstrual and reproductive factors, and none of the 12 common genetic variants we evaluated at the CYP17A1 locus makes a substantial contribution to pancreatic cancer susceptibility in the EPIC cohort.

  • 44.
    Eklöf, Vincy
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Löfgren-Burström, Anna
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Zingmark, Carl
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Edin, Sofia
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Larsson, Pär
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Karling, Pontus
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Alexeyev, Oleg
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Rutegård, Jörgen
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Wikberg, Maria L
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Palmqvist, Richard
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Cancer-associated fecal microbial markers in colorectal cancer detection2017In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 141, no 12, p. 2528-2536Article in journal (Refereed)
    Abstract [en]

    Colorectal cancer (CRC) is the second most common cause of cancer death in the western world. An effective screening program leading to early detection of disease would severely reduce the mortality of CRC. Alterations in the gut microbiota have been linked to CRC, but the potential of microbial markers for use in CRC screening has been largely unstudied. We used a nested case-control study of 238 study subjects to explore the use of microbial markers for clbA+ bacteria harboring the pks pathogenicity island, afa-C+ diffusely adherent Escherichia coli harboring the afa-1 operon, and Fusobacterium nucleatum in stool as potential screening markers for CRC. We found that individual markers for clbA+ bacteria and F. nucleatum were more abundant in stool of patients with CRC, and could predict cancer with a relatively high specificity (81.5% and 76.9%, respectively) and with a sensitivity of 56.4% and 69.2%, respectively. In a combined test of clbA+ bacteria and F. nucleatum, CRC was detected with a specificity of 63.1% and a sensitivity of 84.6%. Our findings support a potential value of microbial factors in stool as putative noninvasive biomarkers for CRC detection. We propose that microbial markers may represent an important future screening strategy for CRC, selecting patients with a "high-risk" microbial pattern to other further diagnostic procedures such as colonoscopy.

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  • 45. Elsir, Tamador
    et al.
    Edqvist, Per-Henrik
    Carlson, Joseph
    Ribom, Dan
    Bergqvist, Michael
    Ekman, Simon
    Popova, Svetlana N
    Alafuzoff, Irina
    Ponten, Fredrik
    Nistér, Monica
    Smits, Anja
    A study of embryonic stem cell-related proteins in human astrocytomas: identification of Nanog as a predictor of survival.2014In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 134, no 5Article in journal (Refereed)
    Abstract [en]

    Recent studies suggest that the regulatory networks controlling the functions of stem cells during development may be abnormally active in human cancers. An embryonic stem cell (ESC) gene signature was found to correlate with a more undifferentiated phenotype of several human cancer types including gliomas, and associated with poor prognosis in breast cancer. In the present study, we used tissue microarrays of 80 low-grade (WHO Grade II) and 98 high-grade human gliomas (WHO Grades III and IV) to investigate the presence of the ESC-related proteins Nanog, Klf4, Oct4, Sox2 and c-Myc by immunohistochemistry. While similar patterns of co-expressed proteins between low- and high-grade gliomas were present, we found up-regulated protein levels of Nanog, Klf4, Oct4 and Sox2 in high-grade gliomas. Survival analysis by Kaplan-Meier analysis revealed a significant shorter survival in the subgroups of low-grade astrocytomas (n = 42) with high levels of Nanog protein (p = 0.0067) and of Klf4 protein (p = 0.0368), in high-grade astrocytomas (n = 85) with high levels of Nanog (p = 0.0042), Klf4 (p = 0.0447), and c-Myc (p = 0.0078) and in glioblastomas only (n = 71) with high levels of Nanog (p = 0.0422) and of c-Myc (p = 0.0256). In the multivariate model, Nanog was identified as an independent prognostic factor in the subgroups of low-grade astrocytomas (p = 0.0039), high-grade astrocytomas (p = 0.0124) and glioblastomas only (p = 0.0544), together with established clinical variables in these tumors. These findings provide further evidence for the joint regulatory pathways of ESC-related proteins in gliomas and identify Nanog as one of the key players in determining clinical outcome of human astrocytomas.

  • 46. Emaus, Marleen J.
    et al.
    van Gils, Carla H.
    Bakker, Marije F.
    Bisschop, Charlotte N. Steins
    Monninkhof, Evelyn M.
    Bueno-de-Mesquita, H. B(as)
    Travier, Noemie
    Berentzen, Tina Landsvig
    Overvad, Kim
    Tjonneland, Anne
    Romieu, Isabelle
    Rinaldi, Sabina
    Chajes, Veronique
    Gunter, Marc J.
    Clavel-Chapelon, Francoise
    Fagherazzi, Guy
    Mesrine, Sylvie
    Chang-Claude, Jenny
    Kaaks, Rudolf
    Boeing, Heiner
    Aleksandrova, Krasimira
    Trichopoulou, Antonia
    Naska, Androniki
    Orfanos, Philippos
    Palli, Domenico
    Agnoli, Claudia
    Tumino, Rosario
    Vineis, Paolo
    Mattiello, Amalia
    Braaten, Tonje
    Borch, Kristin Benjaminsen
    Lund, Eiliv
    Menendez, Virginia
    Sanchez, Maria-Jose
    Navarro, Carmen
    Barricarte, Aurelio
    Amiano, Pilar
    Sund, Malin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Andersson, Anne
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Borgquist, Signe
    Olsson, Asa
    Khaw, Kay-Tee
    Wareham, Nick
    Travis, Ruth C.
    Riboli, Elio
    Peeters, Petra H. M.
    May, Anne M.
    Weight change in middle adulthood and breast cancer risk in the EPIC-PANACEA study2014In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 135, no 12, p. 2887-2899Article in journal (Refereed)
    Abstract [en]

    Long-term weight gain (i.e., weight gain since age 20) has been related to higher risk of postmenopausal breast cancer, but a lower risk of premenopausal breast cancer. The effect of weight change in middle adulthood is unclear. We investigated the association between weight change in middle adulthood (i.e., women aged 40-50 years) and the risk of breast cancer before and after the age of 50. We included female participants of the European Prospective Investigation into Cancer and Nutrition cohort, with information on anthropometric measures at recruitment and after a median follow-up of 4.3 years. Annual weight change was categorized using quintiles taking quintile 2 and 3 as the reference category (-0.44 to 0.36 kg/year). Multivariable Cox proportional hazards regression analysis was used to examine the association. 205,723 women were included and 4,663 incident breast cancer cases were diagnosed during a median follow-up of 7.5 years (from second weight assessment onward). High weight gain (Q5: 0.83-4.98 kg/year) was related to a slightly, but significantly higher breast cancer risk (HRQ5_versus_Q2/3: 1.09, 95% CI: 1.01-1.18). The association was more pronounced for breast cancer diagnosed before or at age 50 (HRQ5_versus_Q2/3: 1.37, 95% CI: 1.02-1.85). Weight loss was not associated with breast cancer risk. There was no evidence for heterogeneity by hormone receptor status. In conclusion, high weight gain in middle adulthood increases the risk of breast cancer. The association seems to be more pronounced for breast cancer diagnosed before or at age 50. Our results illustrate the importance of avoiding weight gain in middle adulthood.

  • 47. Espinosa-Parrilla, Yolanda
    et al.
    Munoz, Xavier
    Bonet, Catalina
    Garcia, Nadia
    Vencesla, Adoracion
    Yiannakouris, Nikos
    Naccarati, Alessio
    Sieri, Sabina
    Panico, Salvatore
    Huerta, Jose M.
    Barricarte, Aurelio
    Menendez, Virginia
    Sanchez-Cantalejo, Emilio
    Dorronsoro, Miren
    Brennan, Paul
    Duarte-Salles, Talita
    Bueno-de-Mesquita, H. B. (As)
    Weiderpass, Elisabete
    Lund, Eiliv
    Clavel-Chapelon, Francoise
    Boutron-Ruault, Marie-Christine
    Racine, Antoine
    Numans, Mattijs E.
    Tumino, Rosario
    Canzian, Federico
    Campa, Daniele
    Sund, Malin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Johansson, Mattias
    Umeå University, Faculty of Medicine, Department of Biobank Research. International Agency for Research on Cancer (IARC-WHO), Lyon, France.
    Ohlsson, Bodil
    Lindkvist, Bjorn
    Overvad, Kim
    Tjonneland, Anne
    Palli, Domenico
    Travis, Ruth C.
    Khaw, Kay-Tee
    Wareham, Nick
    Boeing, Heiner
    Nesi, Gabriella
    Riboli, Elio
    Gonzalez, Carlos A.
    Sala, Nuria
    Genetic association of gastric cancer with miRNA clusters including the cancer-related genes MIR29, MIR25, MIR93 and MIR106: Results from the EPIC-EURGAST study2014In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 135, no 9, p. 2065-2076Article in journal (Refereed)
    Abstract [en]

    MicroRNAs (miRNAs) are post-transcriptional gene regulators involved in a wide range of biological processes including tumorigenesis. Deregulation of miRNA pathways has been associated with cancer but the contribution of their genetic variability to this disorder is poorly known. We analyzed the genetic association of gastric cancer (GC) and its anatomical and histological subtypes, with 133 single-nucleotide polymorphisms (SNPs) tagging 15 isolated miRNAs and 24 miRNA clusters potentially involved in cancer, in 365 GC cases and 1,284 matched controls within the European Prospective Investigation into Cancer and Nutrition cohort. Various SNPs were associated with GC under the log-additive model. Furthermore, several of these miRNAs passed the gene-based permutation test when analyzed according to GC subtypes: three tagSNPs of the miR-29a/miR-29b-1 cluster were associated with diffuse subtype (minimum p-value=1.7 x 10(-4); odds ratio, OR=1.72; 95% confidence interval, CI=1.30-2.28), two tagSNPs of the miR-25/miR-93/miR-106b cluster were associated with cardia GC (minimum p-value=5.38 x 10(-3); OR=0.56, 95% CI=0.37-0.86) and one tagSNP of the miR-363/miR-92a-2/miR-19b-2/miR-20b/miR-18b/miR-106a cluster was associated with noncardia GC (minimum p-value=5.40 x 10(-3); OR=1.41, 95% CI=1.12-1.78). Some functionally validated target genes of these miRNAs are implicated in cancer-related processes such as methylation (DNMT3A, DNMT3B), cell cycle (E2F1, CDKN1A, CDKN1C), apoptosis (BCL2L11, MCL1), angiogenesis (VEGFA) and progression (PIK3R1, MYCN). Furthermore, we identified genetic interactions between variants tagging these miRNAs and variants in their validated target genes. Deregulation of the expression of these miRNAs in GC also supports our findings, altogether suggesting for the fist time that genetic variation in MIR29, MIR25, MIR93 and MIR106b may have a critical role in genetic susceptibility to GC and could contribute to the molecular mechanisms of gastric carcinogenesis.

  • 48. Fanidi, Anouar
    et al.
    Carreras-Torres, Robert
    Larose, Tricia L.
    Yuan, Jian-Min
    Stevens, Victoria L.
    Weinstein, Stephanie J.
    Albanes, Demetrius
    Prentice, Ross
    Pettinger, Mary
    Cai, Qiuyin
    Blot, William J.
    Arslan, Alan A.
    Zeleniuch-Jacquotte, Anne
    McCullough, Marjorie L.
    Le Marchand, Loic
    Wilkens, Lynne R.
    Haiman, Christopher A.
    Zhang, Xuehong
    Stampfer, Meir J.
    Smith-Warner, Stephanie A.
    Giovannucci, Edward
    Giles, Graham G.
    Hodge, Allison M.
    Severi, Gianluca
    Johansson, Mikael
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Grankvist, Kjell
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Langhammer, Arnulf
    Brumpton, Ben M.
    Wang, Renwei
    Gao, Yu-Tang
    Ericson, Ulrika
    Bojesen, Stig E.
    Arnold, Susanne M.
    Koh, Woon-Puay
    Shu, Xiao-Ou
    Xiang, Yong-Bing
    Li, Honglan
    Zheng, Wei
    Lan, Qing
    Visvanathan, Kala
    Hoffman-Bolton, Judith
    Ueland, Per M.
    Midttun, Oivind
    Caporaso, Neil E.
    Purdue, Mark
    Freedman, Neal D.
    Buring, Julie E.
    Lee, I-Min
    Sesso, Howard D.
    Gaziano, J. Michael
    Manjer, Jonas
    Relton, Caroline L.
    Hung, Rayjean J.
    Amos, Chris, I
    Johansson, Mattias
    Brennan, Paul
    Is high vitamin B12 status a cause of lung cancer?2019In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 145, no 6, p. 1499-1503Article in journal (Refereed)
    Abstract [en]

    Vitamin B supplementation can have side effects for human health, including cancer risk. We aimed to elucidate the role of vitamin B12 in lung cancer etiology via direct measurements of pre‐diagnostic circulating vitamin B12 concentrations in a nested case–control study, complemented with a Mendelian randomization (MR) approach in an independent case–control sample. We used pre‐diagnostic biomarker data from 5183 case–control pairs nested within 20 prospective cohorts, and genetic data from 29,266 cases and 56,450 controls. Exposures included directly measured circulating vitamin B12 in pre‐diagnostic blood samples from the nested case–control study, and 8 single nucleotide polymorphisms associated with vitamin B12 concentrations in the MR study. Our main outcome of interest was increased risk for lung cancer, overall and by histological subtype, per increase in circulating vitamin B12 concentrations. We found circulating vitamin B12 to be positively associated with overall lung cancer risk in a dose response fashion (odds ratio for a doubling in B12 [ORlog2B12] = 1.15, 95% confidence interval (95%CI) = 1.06–1.25). The MR analysis based on 8 genetic variants also indicated that genetically determined higher vitamin B12 concentrations were positively associated with overall lung cancer risk (OR per 150 pmol/L standard deviation increase in B12 [ORSD] = 1.08, 95%CI = 1.00–1.16). Considering the consistency of these two independent and complementary analyses, these findings support the hypothesis that high vitamin B12 status increases the risk of lung cancer.

  • 49. Fanidi, Anouar
    et al.
    Relton, Caroline
    Ueland, Per Magne
    Midttun, Øivind
    Vollset, Stein Emil
    Travis, Ruth C.
    Trichopoulou, Antonia
    Lagiou, Pagona
    Trichopoulos, Dimitrios
    Bueno-de-Mesquita, H. B(as)
    Ros, Martine
    Boeing, Heiner
    Tumino, Rosario
    Panico, Salvatore
    Palli, Domenico
    Sieri, Sabina
    Vineis, Paolo
    Sánchez, María-José
    Huerta, José María
    Barricarte Gurrea, Aurelio
    Luján-Barroso, Leila
    Quirós, J. Ramón
    Tjønneland, Anne
    Halkjær, Jytte
    Boutron-Ruault, Marie-Christine
    Clavel-Chapelon, Françoise
    Cadeau, Claire
    Weiderpass, Elisabete
    Johansson, Mikael
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Riboli, Elio
    Brennan, Paul
    Johansson, Mattias
    International Agency for Research on Cancer, Lyon, France.
    A prospective study of one-carbon metabolism biomarkers and cancer of the head and neck and esophagus2015In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 136, no 4, p. 915-927Article in journal (Refereed)
    Abstract [en]

    Experimental and epidemiological data suggest that factors of one-carbon metabolism are important in the pathogenesis of several cancers, but prospective data on head and neck cancer (HNC) and esophagus cancer are limited. The European Prospective Investigation into Cancer and Nutrition (EPIC) study recruited 385,747 participants from 10 countries who donated a blood sample. The current study included 516 cancer cases of the head and neck and esophagus and 516 individually matched controls. Plasma levels of vitamins B2, B6, B9 (folate), B12, and methionine and homocysteine were measured in pre-diagnostic plasma samples and analyzed in relation to HNC and esophagus cancer risk, as well as post-diagnosis all-cause mortality. After controlling for risk factors, study participants with higher levels of homocysteine had elevated risk of HNC, the odds ratio (OR) in conditional analysis when comparing the top and bottom quartiles of homocysteine [ORQ4vs. Q1] being 2.13 (95% confidence interval [95% CI] 1.13-4.00, p for trend 0.009). A slight decrease in HNC risk was also seen among subjects with higher levels of folate (ORQ4vs. Q1 0.63, 95% CI 0.35-1.16, p for trend 0.02). Subgroup analyses by anatomical sub-site indicated particularly strong associations with circulating homocysteine for oral cavity and gum cancer (p for trend 8 x 10(-4)), as well as for oropharynx cancer (p for trend 0.008). Plasma concentrations of the other investigated biomarkers did not display any clear association with risk or survival. In conclusion, study participants with elevated circulating levels of homocysteine had increased risk of developing squamous cell carcinoma of the head and neck. What's new? One-carbon metabolism (OCM) involves the transfer of a carbon unit from methyl donor nutrients to molecules involved in the synthesis and methylation of DNA. As a result, dietary imbalances or deficiencies in nutrients crucial for OCM may affect DNA replication, repair, and regulation, potentially facilitating cancer development. This analysis of circulating levels of OCM nutrients in head and neck cancer and esophageal cancer patients and matched controls reveals an association between elevated levels of the amino acid homocysteine and increased risk of squamous cell carcinoma of the head and neck. Risk was decreased slightly by elevated folate levels.

  • 50. Fedirko, Veronika
    et al.
    Romieu, Isabelle
    Aleksandrova, Krasimira
    Pischon, Tobias
    Trichopoulos, Dimitrios
    Peeters, Petra H.
    Romaguera-Bosch, Dora
    Bueno-de-Mesquita, H. B(as)
    Dahm, Christina C.
    Overvad, Kim
    Chirlaque, Maria-Dolores
    Johansen, Christoffer
    Bidstrup, Pernille E.
    Dalton, Susanne O.
    Gunter, Marc J.
    Wark, Petra A.
    Norat, Teresa
    Halkjaer, Jytte
    Tjonneland, Anne
    Dik, Vincent K.
    Siersema, Peter D.
    Boutron-Ruault, Marie-Christine
    Dossus, Laure
    Bastide, Nadia
    Kuehn, Tilman
    Kaaks, Rudolf
    Boeing, Heiner
    Trichopoulou, Antonia
    Klinaki, Eleni
    Katsoulis, Michalis
    Pala, Valeria
    Panico, Salvatore
    Tumino, Rosario
    Palli, Domenico
    Vineis, Paolo
    Weiderpass, Elisabete
    Skeie, Guri
    Gonzalez, Carlos A.
    Sanchez, Maria-Jose
    Barricarte, Aurelio
    Amiano, Pilar
    Ramon Quiros, J.
    Manjer, Jonas
    Jirstroem, Karin
    Ljuslinder, Ingrid
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Palmqvist, Richard
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Khaw, Kay-Tee
    Wareham, Nick
    Bradbury, Kathryn E.
    Stepien, Magdalena
    Duarte-Salles, Talita
    Riboli, Elio
    Jenab, Mazda
    Pre-diagnostic anthropometry and survival after colorectal cancer diagnosis in Western European populations2014In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 135, no 8, p. 1949-1960Article in journal (Refereed)
    Abstract [en]

    General and abdominal adiposity are associated with a high risk of developing colorectal cancer (CRC), but the role of these exposures on cancer survival has been less studied. The association between pre-diagnostic anthropometric characteristics and CRC-specific and all-cause death was examined among 3,924 men and women diagnosed with CRC between 1992 and 2009 in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Multivariable Cox proportional hazards models were used to calculate hazard ratios (FIRS) and corresponding 95% confidence intervals (as). Over a mean follow-up period of 49 months, 1,309 deaths occurred of which 1,043 (79.7%) were due to CRC. In multivariable analysis, prediagnostic BMI kg/m2 was associated with a high risk for CRC-specific (HR = 1.26, 95% CI = 1.04-1.52) and all-cause (HR = 1.32, 95% CI = 1.12-1.56) death relative to BMI <25 kg/m(2). Every 5 kg/m(2) increase in BMI was associated with a high risk for CRC-specific (HR = 1.10, 95% CI = 1.02-1.19) and all-cause death (HR = 1.12, 95% Cl = 1.05-1.20); and every 10 cm increase in waist circumference was associated with a high risk for CRC-specific (HR = 1.09, 95% Cl = 1.02-1.16) and allcause death (HR= 1.11, 95% CI= 1.05-1.18). Similar associations were observed for waist-to-hip and waist-to-height ratios. Height was not associated with CRC-specific or all-cause death. Associations tended to be stronger among men than in women. Possible interactions by age at diagnosis, cancer stage, tumour location, and hormone replacement therapy use among postmenopausal women were noted. Pre-diagnostic general and abdominal adiposity are associated with lower survival after CRC diagnosis.

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