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983 results on '"Bas Bueno‐de‐Mesquita"'

151. Identification of recessively inherited genetic variants for pancreatic cancer risk

Author

Pavel Soucek, Viktor Hlavac, Markus K. Diener, Daniela Basso, Beatrice Mohelnikova-Duchonova, Balázs Németh, Herman Brenner, Roberto Salvia, Vytautas Kiudelis, Konstantinos Papiris, Domenica Gioffreda, Manuel Gentiluomo, Raffaele Pezzilli, János Novák, Oliver Strobel, Martin Oliverius, Martin Lovecek, John P. Neoptolemos, Paolo Giorgio Arcidiacono, Maria Chiara Petrone, Rita T. Lawlor, Ugo Boggi, Ye Lu, Federico Canzian, Yogesh K. Vashist, Livia Archibugi, Stefano Landi, Krzysztof Jamroziak, Cosimo Sperti, Faik G. Uzunoglu, Pavel Vodicka, Stefania Moz, Andrea Mambrini, Andrea Szentesi, Dezso Kelemen, Maurizio Lucchesi, Péter Hegyi, Gabriele Capurso, Giulia Martina Cavestro, Zdenek Kala, Renata Talar-Wojnarowska, Roger Chammas, Hanneke W. M. van Laarhoven, Luca Morelli, George Theodoropoulos, Mateus Nóbrega Aoki, Daniele Campa, Giuseppe Vanella, Thilo Hackert, Angelo Andriulli, Anna Caterina Milanetto, Sabrina Gloria Giulia Testoni, Xin Gao, Ewa Małecka-Panas, Laura Ginocchi, Marta Puzzono, Angelica Macauda, Olivier R. Busch, Ondrej Strouhal, Audrius Ivanauskas, Bas Bueno-de-Mesquita, Jakob R. Izbicki, William Greenhalf, Silvia Carrara, Francesca Tavano, Feng Guo, Maria Gazouli, Stefano Ermini, and Juozas Kupcinskas

Subjects
Genetics, Hepatology, business.industry, Endocrinology, Diabetes and Metabolism, Pancreatic cancer, Gastroenterology, Genetic variants, medicine, Identification (biology), medicine.disease, business
Published
2021

152. Association between anthropometry and lifestyle factors and risk of B cell lymphoma: an exposome wide analysis

Author

Anne Tjønneland, Claudia Agnoli, Pietro Ferrari, Pilar Amiano, Bas Bueno-de-Mesquita, Miguel Rodríguez-Barranco, Alexandra Nieters, Aurelio Barricarte, Roel Vermeulen, Elisabete Weiderpass, Giovanna Masala, José María Huerta, Marta Solans, Delphine Casabonne, Federico Canzian, Caroline Besson, Florentin Späth, Gianluca Severi, Carlotta Sacerdote, James McKay, Catalina Bonet, Sabine Naudin, Fatemeh Saberi Hosnijeh, Sofia Christakoudi, Heinz Freisling, Rosario Tumino, Kristin Benjaminsen Borch, Rudolf Kaaks, Matthias B. Schulze, Yolanda Benavente, Anja Olsen, Charlotta Rylander, Anika Knuppel, Marie Christine Boutron Ruault, Mats Jerkeman, Immunology, Centre international de Recherche sur le Cancer (CIRC), Institut Gustave Roussy (IGR), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Mode de vie, génétique et santé : études intégratives et transgénérationnelles (U1018 (Équipe 9)), Institut Gustave Roussy (IGR)-Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), 179 2017SGR1085 Kræftens Bekæmpelse, DCS German Cancer Research Center, DKFZ Centre International de Recherche sur le Cancer, CIRC Wellcome Trust, WT: 205212/Z/16/Z National Research Council, NRC Medical Research Council, MRC: MR/M012190/1 Cancer Research UK, CRUK: 14136, C570/A11692, C570/A16491 World Cancer Research Fund, WCRF European Commission, EC Institut National de la Santé et de la Recherche Médicale, Inserm Bundesministerium für Bildung und Forschung, BMBF: 01EO1303 Cancerfonden Ministerie van Volksgezondheid, Welzijn en Sport, VWS Agència de Gestió d'Ajuts Universitaris i de Recerca, AGAUR Ligue Contre le Cancer Vetenskapsrådet, VR NordForsk Associazione Italiana per la Ricerca sul Cancro, AIRC Deutsche Krebshilfe Institut Gustave-Roussy Mutuelle Générale de l'Education Nationale, MGEN European Regional Development Fund, ERDF: ERC2009‐AdG 232997, PI13/00061, PI13/01162, PI14/01219, PI17/01280 Hellenic Health Foundation, HHF, Agència de Gestió d'Ajuts Universitaris i de Recerca (AGAUR), CERCA Programme/Generalitat de Catalunya for institutional support, Grant/Award Number: 2017SGR1085, Associazione Italiana per la Ricerca sul Cancro‐AIRC‐Italy and National Research Council (Italy), Cancer Research UK, Grant/Award Numbers: 14136 (to EPIC‐Norfolk), C570/A11692, C570/A16491, Centro de Investigación Biomédica en Red: Epidemiología y Salud Pública (CIBERESP), (Spain), Danish Cancer Society (Denmark), TRANSCAN/Dutch Cancer Society, Grant/Award Number: 179, NOVEL consortium, Dutch Ministry of Public Health, Welfare and Sports (VWS), Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), European Commission (DG‐SANCO), Federal Ministry of Education and Research (BMBF), German Cancer Aid, German Cancer Research Center (DKFZ), German Federal Ministry of Education and Research, Grant/Award Number: BMBF 01EO1303, German Institute of Human Nutrition Potsdam‐Rehbruecke, Nuthetal (Germany), Institut Gustave Roussy, Institut National de la Sante et de la Recherche Medicale (France), International Agency for Research on Cancer, Ligue Natinale Contre le Cancer, LK Research Funds, Medical Research Council, Grant/Award Numbers: 1000143 (to EPIC‐Norfolk), MR/M012190/1 (to EPIC‐Oxford), Mutuelle Generale de l'Education Nationale, Netherlands Cancer Registry (NKR), Nordforsk, Nordic Centre of Excellence programme on Food, Nutrition and Health (Norway), Spanish Ministry of Economy and Competitiveness ‐ Carlos III Institute of Health cofunded by FEDER funds/European Regional Develpment Fund (ERDF) ‐ a way to build Europe, Grant/Award Numbers: PI13/00061 (to Granada), PI13/01162 (to EPIC‐Murcia), PI17/01280, PI14/01219 (to Barcelona), Statistics Netherlands (The Netherlands), Grant/Award Number: Grant number: ERC2009‐AdG 232997, Swedish Cancer Society, Swedish Research Council and County Councils of Skåne and Vasterbotten (Sweden), the Hellenic Health Foundation (Greece), Wellcome Trust, Grant/Award Number: 205212/Z/16/Z, and World Cancer Research Fund (WCRF) Funding information

Subjects
Oncology, Male, Limfomes, Cancer Research, Lymphoma, Follicular lymphoma, Cohort Studies, 0302 clinical medicine, Risk Factors, Prospective Studies, Càncer, Prospective cohort study, B-cell lymphoma, Cancer, 2. Zero hunger, wide association study, VDP::Medisinske Fag: 700::Helsefag: 800::Samfunnsmedisin, sosialmedisin: 801, Anthropometry, exposome wide association study, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Plasma cell neoplasm, Middle Aged, exposome‐, CANCER, 3. Good health, European Prospective Investigation into Cancer and Nutrition, exposome&#8208, MEDITERRANEAN DIET, 030220 oncology & carcinogenesis, OBESITY, Lymphomas, Female, SMOKING, NON-HODGKIN-LYMPHOMA, Life Sciences & Biomedicine, Cancer Epidemiology, prospective study, NATIONAL-HEALTH, medicine.medical_specialty, Inverse Association, lifestyle, Lymphoma, B-Cell, [SDV.CAN]Life Sciences [q-bio]/Cancer, lymphoma, exposome‐wide association study, exposome, DIETARY-FAT, 03 medical and health sciences, SDG 3 - Good Health and Well-being, Internal medicine, medicine, Humans, 1112 Oncology and Carcinogenesis, Oncology & Carcinogenesis, VALIDITY, Life Style, Cancer och onkologi, Science & Technology, Proportional hazards model, business.industry, medicine.disease, exposome-wide association study, PHYSICAL-ACTIVITY, PROSPECTIVE COHORT, Cancer and Oncology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, VDP::Medical disciplines: 700::Health sciences: 800::Community medicine, Social medicine: 801, business
Abstract

To better understand the role of individual and lifestyle factors in human disease, an exposome‐wide association study was performed to investigate within a single‐study anthropometry measures and lifestyle factors previously associated with B‐cell lymphoma (BCL). Within the European Prospective Investigation into Cancer and nutrition study, 2402 incident BCL cases were diagnosed from 475 426 participants that were followed‐up on average 14 years. Standard and penalized Cox regression models as well as principal component analysis (PCA) were used to evaluate 84 exposures in relation to BCL risk. Standard and penalized Cox regression models showed a positive association between anthropometric measures and BCL and multiple myeloma/plasma cell neoplasm (MM). The penalized Cox models additionally showed the association between several exposures from categories of physical activity, smoking status, medical history, socioeconomic position, diet and BCL and/or the subtypes. PCAs confirmed the individual associations but also showed additional observations. The PC5 including anthropometry, was positively associated with BCL, diffuse large B‐cell lymphoma (DLBCL) and MM. There was a significant positive association between consumption of sugar and confectionary (PC11) and follicular lymphoma risk, and an inverse association between fish and shellfish and Vitamin D (PC15) and DLBCL risk. The PC1 including features of the Mediterranean diet and diet with lower inflammatory score showed an inverse association with BCL risk, while the PC7, including dairy, was positively associated with BCL and DLBCL risk. Physical activity (PC10) was positively associated with DLBCL risk among women. This study provided informative insights on the etiology of BCL., What's new? The “exposome” includes all non‐genetic exposures (e.g. diet, viral, environmental, etc.), with the goal of understanding how those exposures may affect an individual's health. In this study, the authors used a technique called “EWAS” (exposome‐wide association study) to identify multiple factors that are associated with B‐cell lymphoma (BCL) risk. Their results confirm both previously reported risk factors and protective factors. In addition, they identify several previously unknown associations. These new insights, gained via the analysis of multiple exposures, suggest that traditional single‐factor approaches may be suboptimal compared with an EWAS approach.

Published
2020

153. A 584 bp deletion in CTRB2 inhibits chymotrypsin B2 activity and secretion and confers risk of pancreatic cancer

Author

Irene Collins, Federico Canzian, Katelyn Connelly, Loic LeMarchand, Harvey A. Risch, Salvatore Panico, Alison P. Klein, Sumeth Perera, Stephen J. Chanock, Mengmeng Du, Aurelio Barricarte Gurrea, Bas Bueno-de-Mesquita, Marc Thornquist, Gloria M. Petersen, Charles Kooperberg, Xiao-Ou Shu, Brian M. Wolpin, Ashley Jermusyk, Graham G. Giles, Núria Malats, Ulrike Peters, Ruth C. Travis, Phyllis J. Goodman, Jill P. Smith, Christopher J. Westlake, Donghui Li, Mattias Johansson, J. Michael Gaziano, Julie E. Buring, Francisco X. Real, Anne Tjønneland, Stephen Gallinger, Kala Visvanathan, Eric J. Jacobs, Naomi Gordon, Rachel E. Neale, Chen Yuan, Tongwu Zhang, Peter Kraft, Stephen K. Van Den Eeden, Laufey T. Amundadottir, Aidan O’Brien, Ehssan Abdolalizadeh, Jun Zhong, Wei Zheng, Jason W. Hoskins, Rachael Z. Stolzenberg-Solomon, Jianxin Shi, Paige M. Bracci, Laura Beane-Freeman, Daina Eiser, Malin Sund, Demetrius Albanes, and Alan A. Arslan

Subjects
Chymotrypsin, Genotype, Quantitative Trait Loci, Genome-wide association study, Biology, medicine.disease, Molecular biology, Polymorphism, Single Nucleotide, Exon skipping, Article, Pancreatic Neoplasms, Exon, Pancreatic cancer, Case-Control Studies, RNA splicing, Genetics, medicine, Unfolded protein response, biology.protein, Humans, Allele, Genetics (clinical), Genome-Wide Association Study, Sequence Deletion
Abstract

Genome-wide association studies (GWASs) have discovered 20 risk loci in the human genome where germline variants associate with risk of pancreatic ductal adenocarcinoma (PDAC) in populations of European ancestry. Here, we fine-mapped one such locus on chr16q23.1 (rs72802365, p = 2.51 × 10(−17), OR = 1.36, 95% CI = 1.31–1.40) and identified colocalization (PP = 0.87) with aberrant exon 5–7 CTRB2 splicing in pancreatic tissues (p(GTEx) = 1.40 × 10(−69), β(GTEx) = 1.99; p(LTG) = 1.02 × 10(−30), β(LTG) = 1.99). Imputation of a 584 bp structural variant overlapping exon 6 of CTRB2 into the GWAS datasets resulted in a highly significant association with pancreatic cancer risk (p = 2.83 × 10(−16), OR = 1.36, 95% CI = 1.31–1.42), indicating that it may underlie this signal. Exon skipping attributable to the deletion (risk) allele introduces a premature stop codon in exon 7 of CTRB2, yielding a truncated chymotrypsinogen B2 protein that lacks chymotrypsin activity, is poorly secreted, and accumulates intracellularly in the endoplasmic reticulum (ER). We propose that intracellular accumulation of a nonfunctional chymotrypsinogen B2 protein leads to ER stress and pancreatic inflammation, which may explain the increased pancreatic cancer risk in carriers of CTRB2 exon 6 deletion alleles.

Published
2020

154. Blood pressure and risk of cancer in the European Prospective Investigation into Cancer and Nutrition

Author

Dagfinn Aune, Carla H. van Gils, Olatz Mokoroa, Nicholas J. Wareham, Elisabete Weiderpass, Paul Brennan, Heiner Boeing, Sophia Harlid, Anne Tjønneland, Christel Häggström, Paschalis Thriskos, Elio Riboli, Kim Overvad, Sofia Christakoudi, Sabina Sieri, Tilman Kühn, Anne Laure Madika, Heinz Freisling, Tanja Stocks, Marc J. Gunter, Hannah Lennon, Dimitrios Trichopoulos, Artemisia Kakourou, Georgios Markozannes, Rosario Tumino, Manuela M. Bergmann, Anja Olsen, Christina C. Dahm, Antonia Trichopoulou, Roel Vermeulen, Fulvio Ricceri, Marie-Christine Boutron-Ruault, Salvatore Panico, Giovanna Masala, Olle Melander, Anna Karakatsani, Ioanna Tzoulaki, Georgia Martimianaki, Verena Katzke, Gianluca Severi, Mattias Johansson, Bas Bueno-de-Mesquita, Kay-Tee Khaw, Daniel Redondo-Sánchez, Antonio Agudo, Tammy Y.N. Tong, Sandra Colorado-Yohar, Konstantinos K. Tsilidis, Christakoudi, Sofia [0000-0001-9219-4436], Boutron-Ruault, Marie-Christine [0000-0002-5956-5693], Sieri, Sabina [0000-0001-5201-172X], Ricceri, Fulvio [0000-0001-8749-9737], Häggström, Christel [0000-0001-6808-4405], Apollo - University of Cambridge Repository, IRAS OH Epidemiology Chemical Agents, and dIRAS RA-2

Subjects
Male, Cancer Research, association, cancer, cohort, epidemiology, Europe, hypertension, morphology, risk factors, Adult, Aged, Blood Pressure, Cohort Studies, Diet, Female, Humans, Hypertension, Incidence, Middle Aged, Neoplasms, Nutrition Assessment, Risk Factors, Colorectal cancer, THERAPY, COLORECTAL-CANCER, 0302 clinical medicine, RENAL-CELL CARCINOMA, METABOLIC SYNDROME, BODY-SIZE, European Prospective Investigation into Cancer and Nutrition, Oncology, 030220 oncology & carcinogenesis, Life Sciences & Biomedicine, circulatory and respiratory physiology, Cohort study, medicine.medical_specialty, macromolecular substances, Article, 03 medical and health sciences, Breast cancer, Internal medicine, medicine, BREAST-CANCER, 1112 Oncology and Carcinogenesis, cardiovascular diseases, Oncology & Carcinogenesis, Science & Technology, business.industry, INCIDENT HYPERTENSION, Endometrial cancer, Cancer, ENDOMETRIAL CANCER, medicine.disease, Blood pressure, CIGARETTE-SMOKING, Metabolic syndrome, business
Abstract

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.

Published
2020

155. Association of prediagnostic vitamin D status with mortality among colorectal cancer patients differs by common, inherited vitamin D-binding protein isoforms

Author

Tilman Kühn, Christina C. Dahm, Bas Bueno-de-Mesquita, Rosario Tumino, Aurora Perez-Cornago, Mazda Jenab, W. Dana Flanders, Antonia Trichopoulou, David C. Gibbs, Veronika Fedirko, Elisabete Weiderpass, Marjorie L. McCullough, Caroline Y. Um, Inger T. Gram, Björn Gylling, Sandra Colorado-Yohar, Alicia K Heath, and Roberd M. Bostick

Subjects
Male, Cancer Research, 25-HYDROXYVITAMIN D, Colorectal cancer, Vitamin D-binding protein, VARIANTS, Gastroenterology, survival analysis, SERUM, SUPPLEMENTATION, chemistry.chemical_compound, 0302 clinical medicine, cohort studies, single nucleotide polymorphism, Medicine, Protein Isoforms, Prospective Studies, Vitamin D, Aged, 80 and over, GC, Vitamin D-Binding Protein, Hazard ratio, Middle Aged, Prognosis, European Prospective Investigation into Cancer and Nutrition, Oncology, 030220 oncology & carcinogenesis, SURVIVAL, Female, Colorectal Neoplasms, Life Sciences & Biomedicine, Vitamin, medicine.medical_specialty, Single-nucleotide polymorphism, Polymorphism, Single Nucleotide, Article, 03 medical and health sciences, D-RECEPTOR, Internal medicine, Vitamin D and neurology, Humans, COHORT, 1112 Oncology and Carcinogenesis, Oncology & Carcinogenesis, GENOME-WIDE ASSOCIATION, Genetic Association Studies, Aged, Cancer prevention, Science & Technology, business.industry, medicine.disease, PREVENTION, United States, gene-environment interaction, chemistry, business
Abstract

Lower prediagnostic circulating 25-hydroxyvitamin D (25[OH]D)—considered the best marker of total vitamin D exposure—is associated with higher mortality risk among colorectal cancer (CRC) patients. However, it is unknown whether this association differs by the vitamin D-binding protein (GC) isoform Gc2 (encoded by GC rs4588*C>A, Thr436Lys), which may substantially affect vitamin D metabolism and modify associations of 25(OH)D with colorectal neoplasm risk. Prediagnostic 25(OH)D-mortality associations according to Gc2 isoform were estimated using multivariable Cox proportional hazards regression among 1281 CRC cases (635 deaths, 483 from CRC) from two large prospective cohorts conducted in the United States (Cancer Prevention Study-II) and Europe (European Prospective Investigation into Cancer and Nutrition). 25(OH)D measurements were calibrated to a single assay, season standardized, and categorized using Institute of Medicine recommendations (deficient [interaction =.0002). The corresponding HRs for all-cause mortality were 1.80 (95% CI 1.24-2.60) among those with Gc2, and 1.12 (95% CI 0.84-1.51) among those without Gc2 (P interaction =.004). Our findings suggest that the association of prediagnostic vitamin D status with mortality among CRC patients may differ by functional GC isoforms, and patients who inherit the Gc2 isoform (GC rs4588*A) may particularly benefit from higher circulating 25(OH)D for improved CRC prognosis.

Published
2020

156. Physical activity and risks of breast and colorectal cancer : a Mendelian randomisation analysis

Author

Michael O. Woods, Fränzel J.B. van Duijnhoven, Tilman Kühn, Graham G. Giles, Temitope O. Keku, Konstantinos K. Tsilidis, Andrew T. Chan, Mingyang Song, Michael Hoffmeister, Gad Rennert, Tabitha A. Harrison, Anna H. Wu, Kenneth Offit, Mark A. Jenkins, Elizabeth A Platz, Sabina Sieri, Noralane M Lindor, John D. Potter, D Timothy Bishop, Barbara L. Banbury, Anne M. May, Sonja I. Berndt, José María Huerta, Antonia Trichopoulou, Paul D.P. Pharoah, Niki Dimou, Christopher I. Li, Roger L. Milne, Marc J. Gunter, Hermann Brenner, Martha L. Slattery, Catherine M. Tangen, Gianluca Severi, Richard M. Martin, Nabila Kazmi, Ruth C. Travis, Sanford D. Markowitz, Jeroen R. Huyghe, Heather Hampel, Ulrike Peters, John L. Hopper, Brigid M. Lynch, Krasimira Aleksandrova, Alicja Wolk, Merete Ellingjord-Dale, Li Li, Bethany Van Guelpen, Sergi Castellví-Bel, Edward Giovannucci, Steven J Gallinger, Annika Lindblom, Cornelia M. Ulrich, Stephen B. Gruber, Stephanie L. Schmit, Jenny Chang-Claude, Lorena Moreno, Victor Moreno, Nikos Papadimitriou, Stephen N. Thibodeau, Elio Riboli, Sophia Harlid, Polly A. Newcomb, Pavel Vodicka, Demetrius Albanes, Bas Bueno-de-Mesquita, Maria J. Sánchez, Sarah J Lewis, Timothy Robinson, Daniel D Buchanan, Loic Le Marchand, Carlo La Vecchia, Robert E Schoen, Neil Murphy, Giovanna Masala, Evelyn M. Monninkhof, Jane C. Figueiredo, Andrea Gsur, Jochen Hampe, Vittorio Perduca, Li Hsu, Emily White, Peter T. Campbell, School of Public Health - Department of Epidemiology and Biostatistics, Imperial College London, University of Bristol [Bristol], National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH), Department of Epidemiology, German Institute of Human Nutrition, Division of Cancer Epidemiology and Genetics [Bethesda, MD, États-Unis], National Institutes of Health [Bethesda] (NIH)-National Institutes of Health [Bethesda] (NIH), Division of Clinical Epidemiology and Aging Research, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Department for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment [Bilthoven] (RIVM), The Cancer, Ageing and Somatic Mutation Programme [Cambridgeshire, UK], The Wellcome Trust Sanger Institute [Cambridge], Division of Cancer Epidemiology, Samuel Lunenfeld Research Institute, Mount Sinai Hospital [Toronto, Canada] (MSH), University of Melbourne, Harvard School of Public Health, Department of Internal Medicine, Epidemiology, Human Genetics, University of Michigan [Ann Arbor], University of Michigan System-University of Michigan System, Medical Department 1 [Dresden, Germany], Technische Universität Dresden = Dresden University of Technology (TU Dresden), Ohio State University [Columbus] (OSU), FESTO, Universität Stuttgart [Stuttgart], Centre for MEGA Epidemiology, The University of Melbourne, Victoria, Australia, CIBER de Epidemiología y Salud Pública (CIBERESP), Department of Medical Genetics, HMNC Brain Health, Department of Clinical Sciences and Community Health [Milan, Italy], Università degli Studi di Milano [Milano] (UNIMI), University of Hawai‘i [Mānoa] (UHM), Chinese Center for Disease Control and Prevention, Department of Clinical Genetics, Karolinska University Hospital [Stockholm], Mayo Clinic, Case Western Reserve University [Cleveland], Cancer Risk Factors and LifeStyle Epidemiology Unit, Cancer Research and Prevention Institute (ISPO), Julius Center for Health Sciences and Primary Care, University Medical Center [Utrecht], Cancer Epidemiology Centre, Cancer Council Victoria, Biomedical Research Centre Network for Rare Diseases, CIBER de Enfermedades Raras (CIBERER), Memorial Sloane Kettering Cancer Center [New York], Mathématiques Appliquées Paris 5 (MAP5 - UMR 8145), Université Paris Descartes - Paris 5 (UPD5)-Institut National des Sciences Mathématiques et de leurs Interactions (INSMI)-Centre National de la Recherche Scientifique (CNRS), Department of Oncology, University of Cambridge [UK] (CAM), Johns Hopkins Bloomberg School of Public Health [Baltimore], Johns Hopkins University (JHU), Department of Community Medicine and Epidemiology, CHS National Cancer Control Center, School of Public Health [London, UK] (Faculty of Medicine), Andalusian School of Public Health [Granada], Istituto Nazionale dei Tumori, Fred Hutchinson Cancer Research Center [Seattle] (FHCRC), Mayo Clinic [Rochester], University of Oxford [Oxford], WHO Collaborating Center for Nutrition and Health, Unit of Nutritional Epidemiology and Nutrition in Public Health, Dept of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School [Athens]-University of Athens Medical School [Athens], Helmholtz Centre for Ocean Research [Kiel] (GEOMAR), Department of Medical Biosciences and Pathology, Umeå University, Institute of Experimental Medicine, Czech Academy of Sciences [Prague] (CAS), Karolinska Institutet [Stockholm], Nutrition and Metabolism Section, International Agency for Research on Cancer, [Papadimitriou,N, Dimou,N, Gunter,MJ, Murphy,N] Section of Nutrition and Metabolism, International Agency for Research on Cancer, Lyon, France. [Tsilidis,KK] Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece. [Tsilidis,KK, Ellingjord-Dale,M, Riboli,E] Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK. [Banbury,B, Harrison,TA, Hsu,L, Huyghe,JR, Li,CI, Newcomb,PA, Potter,JD, White,E, Peters,U] Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA. [Martin,RM, Kazmi,N] MRC Integrative Epidemiology Unit (IEU), Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK. [Martin,RM, Lewis,SJ, Robinson,TM] Bristol Medical School, Department of Population Health Sciences, University of Bristol, Bristol, UK. [Martin,RM] National Institute for Health Research (NIHR) Bristol Biomedical Research Centre, University Hospitals Bristol NHS Foundation Trust and the University of Bristol, Bristol, UK. [Albanes,D, Berndt,SI] Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MA, USA. [Aleksandrova,K] German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Nuthetal, Germany. [Bishop,DT] Leeds Institute of Cancer and Pathology, University of Leeds, Leeds, UK. [Brenner,H, Hoffmeister,M] Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany. [Brenner,H] Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany. [Brenner,H] German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany. [Buchanan,DD, Giles,GG, Hopper,JL, Jenkins,MA, Lynch,B, Milne,R] Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, VIC, Australia. [Buchanan,DD] Colorectal Oncogenomics Group, Genetic Epidemiology Laboratory, Department of Pathology, The University of Melbourne, Parkville, VIC, Australia. [Buchanan,DD] Genetic Medicine and Family Cancer Clinic, The Royal Melbourne Hospital, Parkville, VIC, Australia [Bueno-de-Mesquita,B] Former senior scientist, Dept. for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment (RIVM), BA Bilthoven, Netherlands. [Bueno-de-Mesquita,B] Former associate professor, Department of Gastroenterology and Hepatology, University Medical Centre, Utrecht, Netherlands. [Bueno-de-Mesquita,B] ormer visiting professor, Dept. of Epidemiology and Biostatistics, The School of Public Health, Imperial College London, St Mary’s Campus, Norfolk Place, London, London, UK. [Bueno-de-Mesquita,B] Former academic Icon / visiting professor, Dept. of Social & Preventive Medicine, Faculty of Medicine, University of Malaya, Pantai Valley, Kuala Lumpur, Malaysia. [Campbell,PT] Behavioral and Epidemiology Research Group, American Cancer Society, Atlanta, GA, USA. [Castellví-Bel,S, Moreno,L] Gastroenterology Department, Hospital Clínic, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), University of Barcelona, Barcelona, Spain. [Chan,AT, Song,M] Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. [Chan,AT, Song,M] Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. [Chang-Claude,J, Kühn,T] Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. [Chang-Claude,J] University Medical Centre Hamburg-Eppendorf, University Cancer Centre Hamburg (UCCH), Hamburg, Germany. [Figueiredo,JC] Department of Medicine, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA. [Figueiredo,JC] Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA. [Gallinger,SJ] Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada. [Giles,GG, Milne,R] Cancer Epidemiology and Intelligence Division, Cancer Council Victoria, Melbourne, VIC, Australia. [Giovannucci,E, Song,M] Department of Epidemiology, Harvard T.H. Chan School of Public Health, Harvard University, Boston, MA, USA. [Giovannucci,E, Song,M] Department of Nutrition, T.H. H, Chan School of Public Health, Boston, MA, USA. [Giovannucci,E] Channing Division of Network Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA. [Gruber,SB, Schmit,SL] Department of Preventive Medicine, USC Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA. [Gsur,A] Institute of Cancer Research, Department of Medicine I, Medical University Vienna, Vienna, Austria. [Hampe,J] Department of Medicine I, University Hospital Dresden, Technische Universität Dresden (TU Dresden), Dresden, Germany. [Hampel,H] Division of Human Genetics, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA. [Harlid,S] Department of Radiation Sciences, Oncology, Umea University, Umea, Sweden. [Hopper,JL] Department of Epidemiology, School of Public Health and Institute of Health and Environment, Seoul National University, Seoul, South Korea. [Hsu,L] Department of Biostatistics, University of Washington, Seattle, WA, USA. [Huerta,JM, Moreno,V, Sánchez,MJ] CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain. [Huerta,JM] Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca, Murcia, Spain. [Keku,TO] Center for Gastrointestinal Biology and Disease, University of North Carolina, Chapel Hill, NC, USA. [La Vecchia,C, Trichopoulou,A] Hellenic Health Foundation, Athens, Greece. [La Vecchia,C] Dept. of Clinical Sciences and Community Health, Università degli Studi di Milano, Milano, Italy. [Le Marchand,L] University of Hawaii Cancer Center, Honolulu, HI, USA. [Li,L] Department of Family Medicine, University of Virginia, Charlottesville, VA, USA. [Lindblom,A] Department of Clinical Genetics, Karolinska University Hospital, Stockholm, Sweden. [Lindblom,A] Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden. [Lindor,NM] Department of Health Science Research, Mayo Clinic, Scottsdale, AZ, USA. [Lynch,B] Physical Activity Laboratory, Baker Heart and Diabetes Institute, Melbourne, VIC, Australia. [Markowitz,SD] Departments of Medicine and Genetics, Case Comprehensive Cancer Center, Case Western Reserve University, and University Hospitals of Cleveland, Cleveland, OH, USA. [Masala,G] Cancer Risk Factors and Life-Style Epidemiology Unit, Institute for Cancer Research, Prevention and Clinical Network - ISPRO, Florence, Italy. [May,AM, Monninkhof,E] Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, GA UTRECHT, Netherlands. [Milne,R] Genetic Epidemiology Laboratory, Department of Pathology, The University of Melbourne, Parkville, VIC, Australia. [Moreno,V] Cancer Prevention and Control Program, Catalan Institute of Oncology-IDIBELL, L’Hospitalet de Llobregat, Barcelona, Spain. [Moreno,V] Department of Clinical Sciences, Faculty of Medicine, University of Barcelona, Barcelona, Spain. [Newcomb,PA] School of Public Health, University of Washington, Seattle, WA, USA. [Offit,K] Clinical Genetics Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY, USA. [Offit,K] Department of Medicine, Weill Cornell Medical College, New York, NY, USA. [Perduca,V, Severi,G] CESP, Fac. de médecine - Univ. ParisSud, Fac. de médecine - UVSQ I, Université Paris-Saclay, Villejuif, France. [Perduca,V, Severi,G] Gustave Roussy, Villejuif, France. [Perduca,V] Laboratoire de Mathématiques Appliquées MAP5 (UMR CNRS 8145), Université Paris Descartes, Paris, France. [Pharoah,PDP] Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK. [Platz,EA] Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA. [Rennert,G] Department of Community Medicine and Epidemiology, Lady Davis Carmel Medical Center, Haifa, Israel. [Rennert,G] 7Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel. [Rennert,G] Clalit National Cancer Control Center, Haifa, Israel. [Sánchez,MJ] Andalusian School of Public Health, Biomedical Research Institute ibs.GRANADA, University of Granada, Granada, Spain. [Schmit,SL] Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA. [Schoen,RE] Department of Medicine and Epidemiology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA. [Sieri,S] Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. [Slattery,ML] Department of Internal Medicine, University of Utah, Salt Lake City, UT, USA. [Tangen,CM] SWOG Statistical Center, Fred Hutchinson Cancer Research Center, Seattle, WA, USA. [Thibodeau,SN] Division of Laboratory Genetics, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA. [Travis,RC] Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK. [Ulrich,CM] Huntsman Cancer Institute and Department of Population Health Sciences, University of Utah, Salt Lake City, UT, USA. [van Duijnhoven,FJB] Division of Human Nutrition, Wageningen University and Research, Wageningen, Netherlands. [Van Guelpen,B] Department of Radiation Sciences, Oncology Unit, Umeå University, Umeå, Sweden. [Van Guelpen,B] Wallenberg Centre for Molecular Medicine, Umeå University, Umeå, Sweden. [Vodicka,P] Department of Molecular Biology of Cancer, Institute of Experimental Medicine of the Czech Academy of Sciences, Prague, Czech Republic. [Vodicka,P] Faculty of Medicine and Biomedical Center in Pilsen, Charles University, Pilsen, Czech Republic. [Vodicka,P] Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University, Prague, Czech Republic. [White,E, Peters,U] Department of Epidemiology, University of Washington, Seattle, WA, USA. [Wolk,A] Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden. [Woods,MO] Memorial University of Newfoundland, Discipline of Genetics, St. John’s, Canada. [Wu,AH] University of Southern California, Preventative Medicine, Los Angeles, CA, USA., This work was supported by the National Cancer Institute, the International Agency for Research on Cancer and a Cancer Research UK program grant (C18281/A19169 to RMM, SJL & NK). RMM was supported by the National Institute for Health Research (NIHR) Bristol Biomedical Research Centre. The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care. The funding sources for BCAC, CCFR, GECCO, and CORECT consortia are presented in detail in the appendix in the Supplementary material., Tsilidis, Konstantinos K [0000-0002-8452-8472], Martin, Richard M [0000-0002-7992-7719], Lewis, Sarah J [0000-0003-4311-6890], Robinson, Timothy M [0000-0003-0933-646X], Timothy Bishop, D [0000-0002-8752-8785], Buchanan, Daniel D [0000-0003-2225-6675], Chan, Andrew T [0000-0001-7284-6767], Giles, Graham G [0000-0003-4946-9099], Gsur, Andrea [0000-0002-9795-1528], Hampe, Jochen [0000-0002-2421-6127], Hampel, Heather [0000-0001-7558-9794], Harlid, Sophia [0000-0001-8540-6891], Harrison, Tabitha A [0000-0002-4173-7530], María Huerta, José [0000-0002-9637-3869], Huyghe, Jeroen R [0000-0001-6027-9806], Jenkins, Mark A [0000-0002-8964-6160], La Vecchia, Carlo [0000-0003-1441-897X], Masala, Giovanna [0000-0002-5758-9069], Milne, Roger [0000-0001-5764-7268], Moreno, Victor [0000-0002-2818-5487], Newcomb, Polly A [0000-0001-8786-0043], Perduca, Vittorio [0000-0003-0339-0473], Pharoah, Paul D P [0000-0001-8494-732X], Potter, John D [0000-0001-5439-1500], Rennert, Gad [0000-0002-8512-068X], Riboli, Elio [0000-0001-6795-6080], Schmit, Stephanie L [0000-0001-5931-1194], Schoen, Robert E [0000-0001-7153-2766], Van Guelpen, Bethany [0000-0002-9692-101X], Wolk, Alicja [0000-0001-7387-6845], Peters, Ulrike [0000-0001-5666-9318], Murphy, Neil [0000-0003-3347-8249], Apollo - University of Cambridge Repository, Tsilidis, Konstantinos K. [0000-0002-8452-8472], Martin, Richard M. [0000-0002-7992-7719], Lewis, Sarah J. [0000-0003-4311-6890], Timothy Bishop, D. [0000-0002-8752-8785], Buchanan, Daniel D. [0000-0003-2225-6675], Chan, Andrew T. [0000-0001-7284-6767], Giles, Graham G. [0000-0003-4946-9099], Harrison, Tabitha A. [0000-0002-4173-7530], Huyghe, Jeroen R. [0000-0001-6027-9806], Jenkins, Mark A. [0000-0002-8964-6160], Newcomb, Polly A. [0000-0001-8786-0043], Pharoah, Paul D. P. [0000-0001-8494-732X], Potter, John D. [0000-0001-5439-1500], Schmit, Stephanie L. [0000-0001-5931-1194], Schoen, Robert E. [0000-0001-7153-2766], and Pharoah, Paul DP [0000-0001-8494-732X]

Subjects
Oncology, Epidemiology, Colorectal cancer, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Accelerometry [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Molecular Epidemiology::Mendelian Randomization Analysis [Medical Subject Headings], Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], 0302 clinical medicine, Breast cancer, Epidemiology of cancer, Accelerometry, Odds Ratio, lcsh:Science, skin and connective tissue diseases, Cancer genetics, ComputingMilieux_MISCELLANEOUS, Cancer, 0303 health sciences, Biobank, 3. Good health, 030220 oncology & carcinogenesis, ICEP, Factores de riesgo, medicine.medical_specialty, Science, 631/67/2324, Diseases::Neoplasms::Neoplasms by Site::Digestive System Neoplasms::Gastrointestinal Neoplasms::Intestinal Neoplasms::Colorectal Neoplasms::Colorectal Neoplasms, Hereditary Nonpolyposis [Medical Subject Headings], Breast Neoplasms/genetics, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, SDG 3 - Good Health and Well-being, Càncer colorectal, Anthropology, Education, Sociology and Social Phenomena::Human Activities::Exercise [Medical Subject Headings], Humans, Epidemiologia, Exercise, VLAG, Cancer och onkologi, 45, 631/67/1347, Odds ratio, Mendelian Randomization Analysis, medicine.disease, Colorectal Neoplasms/genetics, 030104 developmental biology, Analyses, Risk factors, Check Tags::Female [Medical Subject Headings], Cancer and Oncology, lcsh:Q, Breast neoplasms, 0301 basic medicine, 631/67/1504/1885, Nutrition and Disease, General Physics and Astronomy, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability::Risk::Risk Factors [Medical Subject Headings], Risk Factors, Neoplasias colorrectales, Voeding en Ziekte, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability::Odds Ratio [Medical Subject Headings], Multidisciplinary, article, Public Health, Global Health, Social Medicine and Epidemiology, Polymorphism, Single Nucleotide/genetics, Ejercicio físico, Neoplasias de la mama, Female, Colorectal Neoplasms, 631/67, 141, Breast Neoplasms, 45/23, Polymorphism, Single Nucleotide, Colorectal neoplasms, Càncer de mama, Diseases::Pathological Conditions, Signs and Symptoms::Pathologic Processes::Disease Attributes::Disease Susceptibility::Genetic Predisposition to Disease [Medical Subject Headings], Cancer epidemiology, 631/67/68, Internal medicine, Mendelian randomization, medicine, Journal Article, Life Science, Genetic Predisposition to Disease, Diseases::Neoplasms::Neoplasms by Site::Breast Neoplasms [Medical Subject Headings], 030304 developmental biology, Phenomena and Processes::Genetic Phenomena::Genetic Variation::Polymorphism, Genetic::Polymorphism, Single Nucleotide [Medical Subject Headings], business.industry, General Chemistry, Physical fitness, Confidence interval, Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, Condició física
Abstract

Physical activity has been associated with lower risks of breast and colorectal cancer in epidemiological studies; however, it is unknown if these associations are causal or confounded. In two-sample Mendelian randomisation analyses, using summary genetic data from the UK Biobank and GWA consortia, we found that a one standard deviation increment in average acceleration was associated with lower risks of breast cancer (odds ratio [OR]: 0.51, 95% confidence interval [CI]: 0.27 to 0.98, P-value = 0.04) and colorectal cancer (OR: 0.66, 95% CI: 0.48 to 0.90, P-value = 0.01). We found similar magnitude inverse associations for estrogen positive (ER+ve) breast cancer and for colon cancer. Our results support a potentially causal relationship between higher physical activity levels and lower risks of breast cancer and colorectal cancer. Based on these data, the promotion of physical activity is probably an effective strategy in the primary prevention of these commonly diagnosed cancers., United States Department of Health & Human Services National Institutes of Health (NIH) - USA NIH National Cancer Institute (NCI), International Agency for Research on Cancer, Cancer Research UK C18281/A19169, National Institute for Health Research (NIHR)

Published
2020

157. Nutrient-wide association study of 92 foods and nutrients and breast cancer risk

Author

Paolo Vineis, Bas Bueno-de-Mesquita, Anja Olsen, Antonio Agudo, Sofia Christakoudi, Nikos Papadimitriou, Aurelio Barricarte, Ulrika Ericson, Salvatore Panico, Elena Critselis, Konstantinos K. Tsilidis, Guy Fagherazzi, Marije F. Bakker, Piet A. van den Brandt, Elio Riboli, Alicia K Heath, Pilar Amiano, Tilman Kühn, María Dolores Chirlaque, Carla H. van Gils, Paolo Contiero, Patrick Arveux, Inge Huybrechts, Paschalis Thriskos, Mathilde His, María José Sánchez, Karina Standahl Olsen, Heinz Freisling, Antonia Trichopoulou, Isabel Drake, Marc J. Gunter, Marie-Christine Boutron-Ruault, David C. Muller, Giovanna Masala, Miguel Rodríguez-Barranco, Pietro Ferrari, Cristina Lasheras, Fulvio Ricceri, Heiner Boeing, Timothy J. Key, Merete Ellingjord-Dale, Elisabete Weiderpass, Anna Winkvist, Guri Skeie, Renée Turzanski-Fortner, Ioanna Tzoulaki, Matthias B. Schulze, Anna Karakatsani, Ingegerd Johansson, Anne Tjønneland, Francesca Mancini, Cancer Research UK, RS: GROW - R1 - Prevention, RS: CAPHRI - R5 - Optimising Patient Care, and Epidemiologie

Subjects
Dietary Fiber, PREMENOPAUSAL, Cancer Research, dietary fiber intake, postmenopausal women, Cohort Studies, 0302 clinical medicine, Nutrient, Breast cancer, Risk Factors, Surveys and Questionnaires, 80 and over, Medicine, 030212 general & internal medicine, Prospective Studies, Aged, 80 and over, Hazard ratio, Middle Aged, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, 3. Good health, European Prospective Investigation into Cancer and Nutrition, Foods, nutrition, POSTMENOPAUSAL WOMEN, Oncology, 030220 oncology & carcinogenesis, DIETARY FIBER INTAKE, Female, Alcohol, Life Sciences & Biomedicine, Cohort study, Research Article, Adult, QUESTIONNAIRE, Breast Neoplasms, Lower risk, lcsh:RC254-282, Càncer de mama, POOLED ANALYSIS, Fibre, 03 medical and health sciences, Young Adult, SDG 3 - Good Health and Well-being, Environmental health, Journal Article, Humans, 1112 Oncology and Carcinogenesis, VDP::Medisinske Fag: 700, Oncology & Carcinogenesis, Nutrició, METAANALYSIS, Aged, SERUM ESTROGEN CONCENTRATIONS, Nutrition, Cancer och onkologi, Science & Technology, Proportional hazards model, business.industry, SCALE PROSPECTIVE COHORT, Feeding Behavior, Nutrients, medicine.disease, Diet, VDP::Medical disciplines: 700, Nutrition Assessment, Cancer and Oncology, business, Wine intake
Abstract

This work was supported by the World Cancer Research Fund (WCRF UK), as part of the World Cancer Research Fund International grant programme (WCRF 2014/1180 to Konstantinos K Tsilidis). The coordination of EPIC is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by Danish Cancer Society (Denmark); Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l’Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM) (France); German Cancer Aid, German Cancer Research Center (DKFZ), Federal Ministry of Education and Research (BMBF),Deutsche Krebshilfe, Deutsches Krebsforschungszentrum and Federal Ministry of Education and Research (Germany); the Hellenic Health Foundation (Greece); Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy and National Research Council (Italy); Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands); Health Research Fund (FIS), Instituto de Salud Carlos III (ISCIII), Regional Governments of Andalucía, Asturias, Basque Country, Murcia, Navarra, and the Catalan Institute of Oncology (Barcelona) (Spain); Swedish Cancer Society, Swedish Research Council and County Councils of Skåne and Västerbotten (Sweden); Cancer Research UK (14136 to EPIC-Norfolk; C570/A16491 and C8221/A19170 to EPIC-Oxford), Medical Research Council (1000143 to EPIC-Norfolk, MR/ M012190/1 to EPIC-Oxford) (UK)., Heath, A.K., Muller, D.C., Van Den Brandt, P.A., Papadimitriou, N., Critselis, E., Gunter, M., Vineis, P., Weiderpass, E., Fagherazzi, G., Boeing, H., Ferrari, P., Olsen, A., Tjønneland, A., Arveux, P., Boutron-Ruault, M.-C., Mancini, F.R., Kühn, T., Turzanski-Fortner, R., Schulze, M.B., Karakatsani, A., Thriskos, P., Trichopoulou, A., Masala, G., Contiero, P., Ricceri, F., Panico, S., Bueno-De-Mesquita, B., Bakker, M.F., Van Gils, C.H., Olsen, K.S., Skeie, G., Lasheras, C., Agudo, A., Rodríguez-Barranco, M., Sánchez, M.-J., Amiano, P., Chirlaque, M.-D., Barricarte, A., Drake, I., Ericson, U., Johansson, I., Winkvist, A., Key, T., Freisling, H., His, M., Huybrechts, I., Christakoudi, S., Ellingjord-Dale, M., Riboli, E., Tsilidis, K.K., Tzoulaki, I.

Published
2020

158. Consumption of Fish and Long-chain n-3 Polyunsaturated Fatty Acids Is Associated With Reduced Risk of Colorectal Cancer in a Large European Cohort

Author

Magritt Brustad, Veronika Fedirko, Marc J. Gunter, Anja Olsen, Antonia Trichopoulou, Geneviève Nicolas, Anna Karakatsani, Veronique Chajes, Gianluca Severi, Elom K. Aglago, Eva Ardanaz, Aurora Perez-Cornago, Kim Overvad, Cristina Lasheras, Salvatore Panico, Verena Katzke, Bas Bueno-de-Mesquita, José María Huerta, Neil Murphy, Christina C. Dahm, Maria Wennberg, Teresa Norat, Bodil Ohlsson, Elisabete Weiderpass, Antonio Agudo, Heather Ward, Anne Tjønneland, Valeria Pala, Tilman Kühn, Bethany Van Guelpen, Guri Skeie, Rosario Tumino, María José Sánchez, A. M. May, Corinne Casagrande, Jeroen W.G. Derksen, Marie-Christine Boutron-Ruault, Elio Riboli, Agnès Fournier, Sophie Hellstrand, Inge Huybrechts, Georgia Martimianaki, Alessio Naccarati, Tobias Pischon, Amanda J. Cross, Pilar Amiano, Domenico Palli, Centre de recherche en épidémiologie et santé des populations (CESP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), RD06/0020 6236 Kræftens Bekæmpelse, DCS German Cancer Research Center, DKFZ Centre International de Recherche sur le Cancer, CIRC Wellcome Trust, WT: C570/A16491, C8221/A19170, MR/M012190/1 National Research Council, NRC Medical Research Council, MRC British Heart Foundation, BHF Cancer Research UK, CRUK World Cancer Research Fund, WCRF: WCRF 2013/1002 Food Standards Agency, FSA Stroke Association European Commission, EC Institut National de la Santé et de la Recherche Médicale, Inserm Bundesministerium für Bildung und Forschung, BMBF Cancerfonden Ministerie van Volksgezondheid, Welzijn en Sport, VWS Ligue Contre le Cancer Stavros Niarchos Foundation, SNF Instituto de Salud Carlos III, ISCIII Associazione Italiana per la Ricerca sul Cancro, AIRC Deutsche Krebshilfe Associazione Iblea per la Ricerca Epidemiologica, AIRE Institut Gustave-Roussy Mutuelle Générale de l'Education Nationale, MGEN Ministry of Health and Social Solidarity, Greece Fondation Gustave Roussy Hellenic Health Foundation, HHF, Funding Supported by a grant from the World Cancer Research Fund ( WCRF ) to Marc Gunter (grant number: WCRF 2013/1002 ). The coordination of EPIC is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer . The national cohorts are supported by Danish Cancer Society (Denmark), Ligue Contre le Cancer , Institut Gustave Roussy , Mutuelle Générale de l'Education Nationale , and Institut National de la Santé et de la Recherche Médicale ( INSERM ) (France), German Cancer Aid , German Cancer Research Center ( DKFZ ), and Federal Ministry of Education and Research ( BMBF ) (Germany), Hellenic Health Foundation , Stavros Niarchos Foundation , and the Hellenic Ministry of Health and Social Solidarity (Greece), Italian Association for Research on Cancer ( AIRC ), National Research Council , and Associazione Iblea per la Ricerca Epidemiologica (AIRE-ONLUS) Ragusa, Associazione Volontari Italiani Sangu ( AVIS ) Ragusa, Sicilian Government (Italy), Dutch Ministry of Public Health , Welfare and Sports ( VWS ), Netherlands Cancer Registry ( NKR ), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund ( WCRF ), and Statistics Netherlands (the Netherlands), Nordic Center of Excellence Programme on Food, Nutrition and Health (Norway), Health Research Fund (FIS), Regional Governments of Andalucía , Asturias, Basque Country, Murcia (No. 6236) and Navarra, and the Centro de Investigación Biomédica en Red en Epidemiología y Salud Pública and Instituto de Salud Carlos II ( ISCIII RETIC) ( RD06/0020 ) (Spain), Swedish Cancer Society , Swedish Scientific Council , and Regional Government of Skåne and Västerbotten (Sweden), Cancer Research UK , Medical Research Council , Stroke Association , British Heart Foundation , Department of Health , Food Standards Agency , the Wellcome Trust (UK), Cancer Research UK ( 14136 to EPIC-Norfolk, C570/A16491 and C8221/A19170 to EPIC-Oxford), Medical Research Council ( 1000143 to EPIC-Norfolk, MR/M012190/1 to EPIC-Oxford) (United Kingdom)., Funding Supported by a grant from the World Cancer Research Fund (WCRF) to Marc Gunter (grant number: WCRF 2013/1002). The coordination of EPIC is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by Danish Cancer Society (Denmark), Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle G?n?rale de l'Education Nationale, and Institut National de la Sant? et de la Recherche M?dicale (INSERM) (France), German Cancer Aid, German Cancer Research Center (DKFZ), and Federal Ministry of Education and Research (BMBF) (Germany), Hellenic Health Foundation, Stavros Niarchos Foundation, and the Hellenic Ministry of Health and Social Solidarity (Greece), Italian Association for Research on Cancer (AIRC), National Research Council, and Associazione Iblea per la Ricerca Epidemiologica (AIRE-ONLUS) Ragusa, Associazione Volontari Italiani Sangu (AVIS) Ragusa, Sicilian Government (Italy), Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), and Statistics Netherlands (the Netherlands), Health Research Fund (FIS), Regional Governments of Andaluc?a, Asturias, Basque Country, Murcia (No. 6236) and Navarra, and the Centro de Investigaci?n Biom?dica en Red en Epidemiolog?a y Salud P?blica and Instituto de Salud Carlos II (ISCIII RETIC) (RD06/0020) (Spain), Swedish Cancer Society, Swedish Scientific Council, and Regional Government of Sk?ne and V?sterbotten (Sweden), Cancer Research UK, Medical Research Council, Stroke Association, British Heart Foundation, Department of Health, Food Standards Agency, the Wellcome Trust (UK), Cancer Research UK (14136 to EPIC-Norfolk, and C570/A16491 and C8221/A19170 to EPIC-Oxford), Medical Research Council (1000143 to EPIC-Norfolk, MR/M012190/1 to EPIC-Oxford) (United Kingdom).

Subjects
Colorectal cancer, [SDV]Life Sciences [q-bio], Àcids grassos insaturats, Physiology, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Càncer colorectal, Fatty Acids, Omega-3, Medicine, Animals, Humans, Prospective Studies, 2. Zero hunger, chemistry.chemical_classification, Unsaturated fatty acids, Epidemiologic, Gastroenterology & Hepatology, Hepatology, VDP::Medisinske Fag: 700::Helsefag: 800::Samfunnsmedisin, sosialmedisin: 801, business.industry, Gastroenterology, Fishes, 1103 Clinical Sciences, Odds ratio, medicine.disease, Eicosapentaenoic acid, 3. Good health, European Prospective Investigation into Cancer and Nutrition, Diet, chemistry, Seafood, Docosahexaenoic acid, 030220 oncology & carcinogenesis, Omega 3, Cohort, Colonic Neoplasms, Tumorigenesis, 030211 gastroenterology & hepatology, Docosapentaenoic acid, VDP::Medical disciplines: 700::Health sciences: 800::Community medicine, Social medicine: 801, business, Polyunsaturated fatty acid
Abstract

Background & Aims There is an unclear association between intake of fish and long-chain n-3 polyunsaturated fatty acids (n-3 LC-PUFAs) and colorectal cancer (CRC). We examined the association between fish consumption, dietary and circulating levels of n-3 LC-PUFAs, and ratio of n-6:n-3 LC-PUFA with CRC using data from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Methods Dietary intake of fish (total, fatty/oily, lean/white) and n-3 LC-PUFA were estimated by food frequency questionnaires given to 521,324 participants in the EPIC study; among these, 6291 individuals developed CRC (median follow up, 14.9 years). Levels of phospholipid LC-PUFA were measured by gas chromatography in plasma samples from a sub-group of 461 CRC cases and 461 matched individuals without CRC (controls). Multivariable Cox proportional hazards and conditional logistic regression models were used to calculate hazard ratios (HRs) and odds ratios (ORs), respectively, with 95% CIs. Results Total intake of fish (HR for quintile 5 vs 1, 0.88; 95% CI, 0.80–0.96; Ptrend = .005), fatty fish (HR for quintile 5 vs 1, 0.90; 95% CI, 0.82–0.98; Ptrend = .009), and lean fish (HR for quintile 5 vs 1, 0.91; 95% CI, 0.83–1.00; Ptrend = .016) were inversely associated with CRC incidence. Intake of total n-3 LC-PUFA (HR for quintile 5 vs 1, 0.86; 95% CI, 0.78–0.95; Ptrend = .010) was also associated with reduced risk of CRC, whereas dietary ratio of n-6:n-3 LC-PUFA was associated with increased risk of CRC (HR for quintile 5 vs 1, 1.31; 95% CI, 1.18–1.45; Ptrend < .001). Plasma levels of phospholipid n-3 LC-PUFA was not associated with overall CRC risk, but an inverse trend was observed for proximal compared with distal colon cancer (Pheterogeneity = .026). Conclusions In an analysis of dietary patterns of participants in the EPIC study, we found regular consumption of fish, at recommended levels, to be associated with a lower risk of CRC, possibly through exposure to n-3 LC-PUFA. Levels of n-3 LC-PUFA in plasma were not associated with CRC risk, but there may be differences in risk at different regions of the colon.

Published
2020

159. An inverse association between the Mediterranean diet and bladder cancer risk: a pooled analysis of 13 cohort studies

Author

Graham G. Giles, Willem J.A. Witlox, Maria E. Goossens, Roger L. Milne, Inge Huybrechts, Frits H.M. van Osch, Hans-Olov Adami, Maree Brinkman, Maurice P. Zeegers, Elisabete Weiderpass, Emily White, Bas Bueno-de-Mesquita, Piet A. van den Brandt, Anke Wesselius, Sylvia H J Jochems, Complexe Genetica, RS: NUTRIM - R3 - Respiratory & Age-related Health, Genetica & Celbiologie, Epidemiologie, RS: GROW - R1 - Prevention, RS: CAPHRI - R5 - Optimising Patient Care, Department of Medical and Clinical Genetics, and University of Helsinki

Subjects
0301 basic medicine, Oncology, Bladder cancer risk, Mediterranean diet, ALCOHOL-CONSUMPTION, Epidemiology, Medicine (miscellaneous), OLIVE OIL, Disease, Diet, Mediterranean, urologic and male genital diseases, Cohort Studies, 0302 clinical medicine, DESIGN, Prospective cohort study, 2. Zero hunger, Nutrition and Dietetics, Bladder cancer, WOMEN, Original Contribution, Middle Aged, 3. Good health, Europe, 3143 Nutrition, Cohort study, medicine.medical_specialty, Inverse Association, 030209 endocrinology & metabolism, Risk Assessment, ANTIOXIDANT CAPACITY, 03 medical and health sciences, ADHERENCE, Internal medicine, UROTHELIAL CELL-CARCINOMA, medicine, Humans, VDP::Medisinske Fag: 700, Aged, MEAT INTAKE, 030109 nutrition & dietetics, Proportional hazards model, business.industry, MORTALITY, medicine.disease, United Kingdom, United States, VDP::Medical disciplines: 700, Urinary Bladder Neoplasms, business
Abstract

Purpose - The role of diet in bladder carcinogenesis has yet to be established. To date most studies have investigated dietary components individually, rather than as dietary patterns, which may provide stronger evidence for any influence of diet on bladder carcinogenesis. The Mediterranean diet has been associated with many health benefits, but few studies have investigated its association with bladder cancer risk. Methods - We investigated the potential association between the Mediterranean diet score (MDS) and risk of developing bladder cancer by pooling 13 prospective cohort studies included in the BLadder cancer Epidemiology and Nutritional Determinants (BLEND) study and applying a Cox regression analysis. Results - Dietary data from 646,222 study participants, including 3639 incident bladder cancer cases, were analysed. We observed an inverse association between Mediterranean diet and bladder cancer risk (HRhigh 0.85 [95% CI 0.77, 0.93]). When stratifying the results on non-muscle-invasive or muscle-invasive disease or sex the association remained similar and the HR estimate was consistently below 1.00 both for medium and high adherence to the Mediterranean diet. A consistent association was observed when disregarding fat or alcohol intake. Conclusion - We found evidence that adherence to the Mediterranean diet was associated with reduced risk of developing bladder cancer, suggesting a positive effect of the diet as a whole and not just one component.

Published
2020

160. Alkylresorcinols (biomarkers of whole grain intake), cereal fibre intake and metabolic profile - results from a European study

Author

Krasimira Aleksandrova, Elisabete Weiderpass, Cecilie Kyrø, Anne Tjonnelandl, Isabelle Romieu, Birthe Lykke Thomsen, Rikard Landberg, Anja Olsen, Bas Bueno-de-Mesquita, Mazda Jenab, Carl Brunius, Izabela Biskup, Yunxia Lu, Elio Riboli, and Anne Kirstine Eriksen

Subjects
Cereal fiber, Nutrition and Dietetics, food and beverages, Medicine (miscellaneous), Food science, Cereal fibre, Biology, Metabolic profile, Whole grains
Abstract

Background:High intakes of whole-grains and cereal fiber have been consistently associated with lower risk of cardiometabolic diseases in observational studies. Yet, improved understanding about the underlying mechanisms is needed. We hypothesized that cereal fiber and whole-grain are associated with beneficial metabolic marker profiles.Aim:To investigate if cereal fiber intake, estimated by food frequency questionnaires and plasma total alkylresorcinols concentrations as well as the C17:0/C21:0-ratio in plasma as biomarkers of whole-grain wheat and rye intake or the relative whole-grain rye to wheat intake, respectively, were associated with metabolic biomarkers.Design:A cross-sectional study conducted to investigate the associations between alkylresorcinols as biomarker of whole-grain wheat and rye intake, cereal fiber and selected metabolic biomarkers among 954 participants of the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Cereal fiber intake was assessed by FFQ and whole grain wheat and rye were reflected by biomarkers analyzed in plasma samples, i.e. total alkylresorcinol (AR). Moreover, the ratio of two of the five measured alkylresorcinols (AR C17:0/C21:0 ratio) was used as an indicator of whole-grain source (wheat or rye). Metabolic biomarkers (HbA1c, C-peptide, IGFBP-1, IGFBP-2, total cholesterol, LDL, HDL, triglycerides, apolipoprotein A-I (apoA), apolipoprotein B (ApoB) and CRP) were measured in blood samples. All biomarkers were already measured for nested case-control studies of colorectal cancer matched based on sex, study center, age at blood collection, date and time of blood collection, fasting status. Women were further matched by menopausal status, phase of menstrual cycle, and use of oral contraceptives or hormone replacement therapy at time of blood collection. Multivariable linear regression analysis was used to investigate the relationship between exposure variables metabolic biomarkers adjusted for case-control status and common confounders.Results:No associations were found between cereal fiber intake and the metabolic markers. However, whole-grain wheat and rye intake, reflected by total AR, was associated with a lower concentration of the inflammation marker CRP. The alkylresorcinol C17:0/C21:0 ratio was not associated with any of the measured metabolic markers in this cohort.Conclusion:Overall, we found no support for an association between cereal fibre intake, whole grain wheat and rye intake reflected by biomarkers and metabolic markers in the present cohort. One exception was the finding of an inverse association between whole grain biomarkers and CRP. Prospective studies or RCTs are warranted to confirm our findings.

Published
2020

161. A Transcriptome-Wide Association Study Identifies Novel Candidate Susceptibility Genes for Pancreatic Cancer

Author

William R. Bamlet, Alpa V. Patel, Mingfeng Zhang, Eric J. Jacobs, Tongwu Zhang, Evelina Mocci, Demetrius Albanes, Nilanjan Chatterjee, Alan A. Arslan, Phyllis J. Goodman, Wenming Xiao, Irene Collins, Ghislaine Scelo, Howard D. Sesso, Manolis Kogevinas, Lang Wu, Patricia Hartge, Manal Hasan, Jill P. Smith, Herbert Yu, Laufey T. Amundadottir, Geoffrey S. Tobias, Nathaniel Rothman, Jean Wactawski-Wende, Mengmeng Du, Edward Giovannucci, Stephen K. Van Den Eeden, Roger L. Milne, Irene Orlow, Elizabeth A. Holly, Kathy J. Helzlsouer, Miquel Porta, Ulrike Peters, Harvey A. Risch, Eric J. Duell, Steven Gallinger, Paige M. Bracci, Charles Kooperberg, Michael Goggins, Federico Canzian, Antonia Trichopoulou, Lei Song, Robert J. Kurtz, Brian M. Wolpin, Anne Zeleniuch-Jacquotte, Stephen J. Chanock, Gianluca Severi, Christopher A. Haiman, Loic LeMarchand, Ann L. Oberg, Jason W. Hoskins, Alison P. Klein, Kala Visvanathan, Gary E. Goodman, Gabriella Andreotti, Donghui Li, Charles C. Chung, Michelle Cotterchio, Lauren K. Brais, Satu Männistö, Núria Malats, Jianxin Shi, Charles S. Fuchs, Wei Zheng, Peter Kraft, Robert N. Hoover, J. Michael Gaziano, Erica J. Childs, Nicolas Wentzensen, Kai Yu, Paul Brennan, Mark D. Thornquist, Julie E. Buring, Anne Tjønneland, Jun Zhong, Kevin M. Brown, Ofure Obazee, Rachael Z. Stolzenberg-Solomon, Sabina Sieri, Bas Bueno-de-Mesquita, Debra T. Silverman, Ana Babic, Sonja I. Berndt, Chen Yuan, Ayelet Borgida, Rachel E. Neale, Eric A. Klein, Gloria M. Petersen, Xiao-Ou Shu, Kimmie Ng, Ashley Jermusyk, Graham G. Giles, Laura Beane-Freeman, Emily White, Malin Sund, Centre international de Recherche sur le Cancer (CIRC), Centre de recherche en épidémiologie et santé des populations (CESP), and Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay

Subjects
2. Zero hunger, Genetics, 0303 health sciences, Cancer Research, Candidate gene, [SDV]Life Sciences [q-bio], Genome-wide association study, Quantitative trait locus, Biology, medicine.disease, 3. Good health, Transcriptome, 03 medical and health sciences, 0302 clinical medicine, medicine.anatomical_structure, Oncology, 030220 oncology & carcinogenesis, Pancreatic cancer, Genotype, medicine, PDX1, Pancreas, 030304 developmental biology
Abstract

Background Although 20 pancreatic cancer susceptibility loci have been identified through genome-wide association studies in individuals of European ancestry, much of its heritability remains unexplained and the genes responsible largely unknown. Methods To discover novel pancreatic cancer risk loci and possible causal genes, we performed a pancreatic cancer transcriptome-wide association study in Europeans using three approaches: FUSION, MetaXcan, and Summary-MulTiXcan. We integrated genome-wide association studies summary statistics from 9040 pancreatic cancer cases and 12 496 controls, with gene expression prediction models built using transcriptome data from histologically normal pancreatic tissue samples (NCI Laboratory of Translational Genomics [n = 95] and Genotype-Tissue Expression v7 [n = 174] datasets) and data from 48 different tissues (Genotype-Tissue Expression v7, n = 74–421 samples). Results We identified 25 genes whose genetically predicted expression was statistically significantly associated with pancreatic cancer risk (false discovery rate < .05), including 14 candidate genes at 11 novel loci (1p36.12: CELA3B; 9q31.1: SMC2, SMC2-AS1; 10q23.31: RP11-80H5.9; 12q13.13: SMUG1; 14q32.33: BTBD6; 15q23: HEXA; 15q26.1: RCCD1; 17q12: PNMT, CDK12, PGAP3; 17q22: SUPT4H1; 18q11.22: RP11-888D10.3; and 19p13.11: PGPEP1) and 11 at six known risk loci (5p15.33: TERT, CLPTM1L, ZDHHC11B; 7p14.1: INHBA; 9q34.2: ABO; 13q12.2: PDX1; 13q22.1: KLF5; and 16q23.1: WDR59, CFDP1, BCAR1, TMEM170A). The association for 12 of these genes (CELA3B, SMC2, and PNMT at novel risk loci and TERT, CLPTM1L, INHBA, ABO, PDX1, KLF5, WDR59, CFDP1, and BCAR1 at known loci) remained statistically significant after Bonferroni correction. Conclusions By integrating gene expression and genotype data, we identified novel pancreatic cancer risk loci and candidate functional genes that warrant further investigation.

Published
2020

162. Antibody Responses to Helicobacter pylori and Risk of Developing Colorectal Cancer in a European Cohort

Author

Kristin Benjaminsen Borch, Catherine Dong, Elisabete Weiderpass, Elio Riboli, Antonia Trichopoulou, Rudolf Kaaks, Claudia Agnoli, Michael Pawlita, Franck Carbonnel, Roel Vermeulen, Heiner Boeing, David J. Hughes, Amanda J. Cross, Julia Butt, Bethany Van Guelpen, Liher Imaz, Marc J. Gunter, Semi Zouiouich, José Ramón Quirós, Cecilie Kyrø, Mazda Jenab, Inger T. Gram, Aurora Perez-Cornago, Matthias B. Schulze, Alicia K Heath, Carlotta Sacerdote, Rosario Tumino, Eva Ardanaz, Jin Young Park, Carmen Santiuste, Anna Karakatsani, Domenico Palli, Tim Waterboer, Bas Bueno-de-Mesquita, Anne Tjønneland, Miguel Rodríguez-Barranco, Carlo La Vecchia, Antonio Agudo, Tilman Kühn, Marie-Christine Boutron-Ruault, Salvatore Panico, Sophia Harlid, Centre international de Recherche sur le Cancer (CIRC), Centre de recherche en épidémiologie et santé des populations (CESP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Institut Gustave Roussy (IGR), Mode de vie, génétique et santé : études intégratives et transgénérationnelles (U1018 (Équipe 9)), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut Gustave Roussy (IGR), and AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre)

Subjects
0301 basic medicine, Male, medicine.medical_specialty, Colorectal cancer, Epidemiology, [SDV]Life Sciences [q-bio], Gastroenterology, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Internal medicine, Medicine, Humans, Helicobacter, Prospective Studies, Prospective cohort study, 11 Medical and Health Sciences, biology, Helicobacter pylori, business.industry, Cancer, Odds ratio, Middle Aged, biology.organism_classification, medicine.disease, bacterial infections and mycoses, digestive system diseases, 3. Good health, European Prospective Investigation into Cancer and Nutrition, Europe, 030104 developmental biology, Oncology, 030220 oncology & carcinogenesis, Case-Control Studies, Cohort, Antibody Formation, Female, business, Colorectal Neoplasms
Abstract

Background: While Helicobacter pylori (H. pylori) is the major cause of gastric cancer, it has also been suggested to be involved in colorectal cancer development. However, prospective studies addressing H. pylori and colorectal cancer are sparse and inconclusive. We assessed the association of antibody responses to H. pylori proteins with colorectal cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Methods: We applied H. pylori multiplex serology to measure antibody responses to 13 H. pylori proteins in prediagnostic serum samples from 485 colorectal cancer cases and 485 matched controls nested within the EPIC study. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using multivariable conditional logistic regression to estimate the association of H. pylori overall and protein-specific seropositivity with odds of developing colorectal cancer. Results: Fifty-one percent of colorectal cancer cases were H. pylori seropositive compared with 44% of controls, resulting in an OR of 1.36 (95% CI, 1.00–1.85). Among the 13 individual H. pylori proteins, the association was driven mostly by seropositivity to Helicobacter cysteine-rich protein C (HcpC; OR: 1.66; 95% CI, 1.19–2.30) and Vacuolating cytotoxin A (VacA) (OR: 1.34; 95% CI, 0.99–1.82), the latter being nonstatistically significant only in the fully adjusted model. Conclusions: In this prospective multicenter European study, antibody responses to H. pylori proteins, specifically HcpC and VacA, were associated with an increased risk of developing colorectal cancer. Impact: Biological mechanisms for a potential causal role of H. pylori in colorectal carcinogenesis need to be elucidated, and subsequently whether H. pylori eradication may decrease colorectal cancer incidence.

Published
2020

163. Gallbladder disease, cholecystectomy, and pancreatic cancer risk in the International Pancreatic Cancer Case-Control Consortium (PanC4)

Author

Valentina Rosato, Eva Negri, Cristina Bosetti, Núria Malats, Paulina Gomez-Rubio, PanGenEU Consortium, Patrick Maisonneuve, Anthony B. Miller, H. Bas Bueno-de-Mesquita, Peter A. Baghurst, Witold Zatonski, Gloria M. Petersen, Ghislaine Scelo, Ivana Holcatova, Eleonora Fabianova, Diego Serraino, Sara H. Olson, Jesús Vioque, Pagona Lagiou, Eric J. Duell, Paolo Boffetta, Carlo La Vecchia, V. Rosato, E. Negri, C. Bosetti, N. Malat, P. Gomez-Rubio, Consortium PanGenEU, P. Maisonneuve, A. B. Miller, H. B. Bueno-de-Mesquita, P. A. Baghurst, W. Zatonski, G. M. Petersen, G. Scelo, I. Holcatova, E. Fabianova, D. Serraino, S. H. Olson, J. Vioque, P. Lagiou, E. J. Duell, P. Boffetta, and C. La Vecchia

Subjects
Male, Cancer Research, medicine.medical_specialty, Epidemiology, medicine.medical_treatment, Gallbladder disease, pancreatic cancer, Gallbladder Diseases, cholecystectomy, Gastroenterology, risks factors, 03 medical and health sciences, 0302 clinical medicine, gallbladder disease, Risk Factors, Internal medicine, Pancreatic cancer, Humans, Medicine, risk factors, pooled analysi, Cholecystectomy, Medical history, 030212 general & internal medicine, Aged, case-control-studie, business.industry, case-control studies, Public Health, Environmental and Occupational Health, Case-control study, International Agencies, Odds ratio, Middle Aged, Prognosis, medicine.disease, Confidence interval, Pancreatic Neoplasms, Oncology, Case-Control Studies, 030220 oncology & carcinogenesis, Adenocarcinoma, Female, pooled analysis, business
Abstract

BACKGROUND: The association among gallbladder disease, cholecystectomy, and pancreatic cancer is unclear. Moreover, time interval between gallbladder disease or cholecystectomy and pancreatic cancer diagnosis is not considered in most previous studies. AIM: To quantify the association among gallbladder disease, cholecystectomy, and pancreatic cancer, considering time since first diagnosis of gallbladder disease or cholecystectomy. METHODS: We used data from nine case-control studies within the Pancreatic Cancer Case-Control Consortium, including 5760 cases of adenocarcinoma of the exocrine pancreas and 8437 controls. We estimated pooled odds ratios and the corresponding 95% confidence intervals by estimating study-specific odds ratios through multivariable unconditional logistic regression models, and then pooling the obtained estimates using fixed-effects models. RESULTS: Compared with patients with no history of gallbladder disease, the pooled odds ratio of pancreatic cancer was 1.69 (95% confidence interval, 1.51-1.88) for patients reporting a history of gallbladder disease. The odds ratio was 4.90 (95% confidence interval, 3.45-6.97) for gallbladder disease diagnosed

Published
2020

164. Predicted basal metabolic rate and cancer risk in the European Prospective Investigation into Cancer and Nutrition

Author

Elisabete Weiderpass, Kim Overvad, Giovanna Masala, Guy Fagherazzi, Rudolf Kaaks, Daniel Redondo-Sánchez, Sabina Rinaldi, Ulrica Ericson, Dagfinn Aune, Pilar Amiano, Therese Haugdahl Nøst, Antonia Trichopoulou, Rosario Tumino, Paula Jakszyn, Neil Murphy, Elio Riboli, Tilman Kühn, Francesca Mancini, Heinz Freisling, Bas Bueno-de-Mesquita, Marie-Christine Boutron-Ruault, Maria Santucci de Magistris, Inge Huybrechts, Marc J. Gunter, Carlotta Sacerdote, Nathalie Kliemann, Christina C. Dahm, Vivian Viallon, Vittorio Krogh, Lena Maria Nilsson, Isabel Drake, Anne M. May, Heiner Boeing, Matthias B. Schulze, Carlo La Vecchia, Anne Tjønneland, Anna Karakatsani, Aurelio Barricarte Gurrea, Konstantinos K. Tsilidis, María Dolores Chirlaque, José Ramón Quirós, Centre international de Recherche sur le Cancer (CIRC), Université de Paris-Saclay [Villejuif], Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Deutsche Krebshilfe Cancer Research UK, CRUK: C8221/A19170, 14136, C570/A16491 Ligue Contre le Cancer Bundesministerium für Bildung und Forschung, BMBF Bundesministerium für Bildung und Forschung, BMBF Institut National de la Santé et de la Recherche Médicale, Inserm Kræftens Bekæmpelse, DCS Research Councils UK, RCUK Health and Medical Research Fund, HMRF: FIS Zorginstituut Nederland, ZIN PI13/01162, PI13/00061 World Cancer Research Fund, WCRF: ERC‐2009‐AdG 232997 Associazione Italiana per la Ricerca sul Cancro, AIRC National Research Council, NRC Ecumenical Project for International Cooperation, EPIC Institut National de la Santé et de la Recherche Médicale, Inserm European Commission, EU Centre International de Recherche sur le Cancer, CIRC Norway Deutsches Krebsforschungszentrum, DKFZ: DKFZ World Cancer Research Fund, WCRF Cancerfonden NordForsk Medical Research Council, MRC: MR/M012190/1, 1000143, The authors would like to thank the EPIC study participants and staff for their valuable contribution to this research. The authors would also like to thank Mr Bertrand Hemon for his support in preparing the databases and Dr Joseph Rothwell for his support in creating the figures. The coordination of EPIC is financially supported by the European Commission (DGSANCO) and the International Agency for Research on Cancer. The national cohorts are supported by Danish Cancer Society (Denmark), Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l'Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM, France), German Cancer Aid, German Cancer Research Center (DKFZ), Federal Ministry of Education and Research (BMBF, Germany), the Hellenic Health Foundation (Greece), Associazione Italiana per la Ricerca sul Cancro‐AIRC‐Italy and National Research Council (Italy), Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), ERC‐2009‐AdG 232997 and Nordforsk, Nordic Centre of Excellence Programme on Food, Nutrition and Health (Norway), Health Research Fund (FIS) of the Spanish Ministry of Health (FIS, PI13/00061 to Granada, PI13/01162 to EPIC‐Murcia), Regional Governments of Andalucía, Asturias, Basque Country, Murcia and Navarra and the Catalan Institute of Oncology (Spain), Swedish Cancer Society, Swedish Research Council and County Councils of Skåne and Västerbotten (Sweden), Cancer Research UK (14136 to EPIC‐Norfolk, C570/A16491 and C8221/A19170 to EPIC‐Oxford), Medical Research Council (1000143 to EPIC‐Norfolk, MR/M012190/1 to EPIC‐Oxford, and United Kingdom).

Subjects
Oncology, Adult, Male, metabolic disorder, Cancer Research, medicine.medical_specialty, obesity, [SDV.CAN]Life Sciences [q-bio]/Cancer, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Neoplasms, medicine, Humans, cancer, 1112 Oncology and Carcinogenesis, Oncology & Carcinogenesis, Prospective Studies, Risk factor, Càncer, Nutrició, Aged, Cancer, Nutrition, Sex Characteristics, business.industry, Incidence (epidemiology), Incidence, Hazard ratio, Metabolic disorder, Middle Aged, medicine.disease, Obesity, 3. Good health, European Prospective Investigation into Cancer and Nutrition, Europe, Nutrition Assessment, 030220 oncology & carcinogenesis, Basal metabolic rate, basal metabolic rate, Female, Basal Metabolism, business
Abstract

Emerging evidence suggests that a metabolic profile associated with obesity may be a more relevant risk factor for some cancers than adiposity per se. Basal metabolic rate (BMR) is an indicator of overall body metabolism and may be a proxy for the impact of a specific metabolic profile on cancer risk. Therefore, we investigated the association of predicted BMR with incidence of 13 obesity-related cancers in the European Prospective Investigation into Cancer and Nutrition (EPIC). BMR at baseline was calculated using the WHO/FAO/UNU equations and the relationships between BMR and cancer risk were investigated using multivariable Cox proportional hazards regression models. A total of 141,295 men and 317,613 women, with a mean follow-up of 14 years were included in the analysis. Overall, higher BMR was associated with a greater risk for most cancers that have been linked with obesity. However, among normal weight participants, higher BMR was associated with elevated risks of esophageal adenocarcinoma (hazard ratio per 1-standard deviation change in BMR [HR 1-SD]: 2.46; 95% CI 1.20; 5.03) and distal colon cancer (HR 1-SD: 1.33; 95% CI 1.001; 1.77) among men and with proximal colon (HR 1-SD: 1.16; 95% CI 1.01; 1.35), pancreatic (HR 1-SD: 1.37; 95% CI 1.13; 1.66), thyroid (HR 1-SD: 1.65; 95% CI 1.33; 2.05), postmenopausal breast (HR 1-SD: 1.17; 95% CI 1.11; 1.22) and endometrial (HR 1-SD: 1.20; 95% CI 1.03; 1.40) cancers in women. These results indicate that higher BMR may be an indicator of a metabolic phenotype associated with risk of certain cancer types, and may be a useful predictor of cancer risk independent of body fatness.

Published
2020

165. Menstrual Factors, Reproductive History, Hormone Use, and Urothelial Carcinoma Risk: AProspective Study in the EPIC Cohort

Author

Aurora Perez-Cornago, Veronica Sciannameo, Salvatore Panico, Domenico Palli, Pilar Amiano, Marit Waaseth, Tilman Kühn, Kay-Tee Khaw, Tanja Stocks, Fredrik Liedberg, Lambertus A. Kiemeney, Carla H. van Gils, Anne Tjønneland, Neil Murphy, María José Sánchez, Leila Lujan-Barroso, Christel Häggström, Amanda J. Cross, Heiner Boeing, Bas Bueno-de-Mesquita, Raul Zamora-Ros, Nina Roswall, Marc J. Gunter, Renée T. Fortner, Inger T. Gram, Kim Overvad, Vittorio Krogh, Börje Ljungberg, Amalia Mattiello, Eric J. Duell, Saverio Caini, Antonia Trichopoulou, Elisabete Weiderpass, Virginia Menéndez, Iris Cervenka, Rosario Tumino, Carmen Santiuste, Agnès Fournier, Edoardo Botteri, Aurelio Barricarte, Eleni Peppa, Eiliv Lund, Marina Kvaskoff, N. Charlotte Onland-Moret, and Anna Karakatsani

Subjects
0301 basic medicine, Oncology, Epidemiology, IMPACT, THERAPY, 0302 clinical medicine, Pregnancy, Risk Factors, Prospective Studies, Child, Prospective cohort study, Reproductive History, 11 Medical and Health Sciences, Bladder cancer, WOMEN, ASSOCIATION, European Prospective Investigation into Cancer and Nutrition, Menstruation, ESTROGEN, 030220 oncology & carcinogenesis, Urological cancers Radboud Institute for Health Sciences [Radboudumc 15], Cohort, Female, SMOKING, Developed country, EXPRESSION, medicine.medical_specialty, Adolescent, Hormone Replacement Therapy, Càncer de bufeta, DIET, 03 medical and health sciences, All institutes and research themes of the Radboud University Medical Center, Internal medicine, medicine, Humans, Menstrual Cycle, VDP::Medical disciplines: 700::Clinical medical disciplines: 750::Oncology: 762, Proportional hazards model, business.industry, medicine.disease, Hormones, VDP::Medisinske Fag: 700::Klinisk medisinske fag: 750::Onkologi: 762, 030104 developmental biology, BLADDER-CANCER RISK, SEX-HORMONES, business, Hormone, Menstruació
Abstract

Background: Urothelial carcinoma is the predominant (95%) bladder cancer subtype in industrialized nations. Animal and epidemiologic human studies suggest that hormonal factors may influence urothelial carcinoma risk. Methods: We used an analytic cohort of 333,919 women from the European Prospective Investigation into Cancer and Nutrition Cohort. Associations between hormonal factors and incident urothelial carcinoma (overall and by tumor grade, tumor aggressiveness, and non–muscle-invasive urothelial carcinoma) risk were evaluated using Cox proportional hazards models. Results: During a mean of 15 years of follow-up, 529 women developed urothelial carcinoma. In a model including number of full-term pregnancies (FTP), menopausal status, and menopausal hormone therapy (MHT), number of FTP was inversely associated with urothelial carcinoma risk (HR≥5vs1 = 0.48; 0.25–0.90; Ptrend in parous women = 0.010) and MHT use (compared with nonuse) was positively associated with urothelial carcinoma risk (HR = 1.27; 1.03–1.57), but no dose response by years of MHT use was observed. No modification of HRs by smoking status was observed. Finally, sensitivity analyses in never smokers showed similar HR patterns for the number of FTP, while no association between MHT use and urothelial carcinoma risk was observed. Association between MHT use and urothelial carcinoma risk remained significant only in current smokers. No heterogeneity of the risk estimations in the final model was observed by tumor aggressiveness or by tumor grade. A positive association between MTH use and non–muscle-invasive urothelial carcinoma risk was observed. Conclusions: Our results support that increasing the number of FTP may reduce urothelial carcinoma risk. Impact: More detailed studies on parity are needed to understand the possible effects of perinatal hormone changes in urothelial cells.

Published
2020

166. Coffee and tea consumption and risk of prostate cancer in the European Prospective Investigation into Cancer and Nutrition

Author

Aurelio Barricarte, Tilman Kühn, Nikos Papadimitriou, Rosario Tumino, Elio Riboli, Lena Maria Nilsson, Dimitrios Trichopoulos, Dagfinn Aune, Bas Bueno-de-Mesquita, Kim Overvad, Ruth C. Travis, Nerea Larrañaga, Bodil Hammer Bech, Peter Wallström, Antonia Trichopoulou, Christina Bamia, Maria Luisa Redondo, Heiner Boeing, Valerie Cayssials, Rudolf Kaaks, Carlotta Sacerdote, Anne Tjønneland, Ioanna Tzoulaki, Neil Murphy, Anna Karakatsani, Aurora Perez-Cornago, Rikard Landberg, Anastasia Kotanidou, Cecilie Kyrø, Sara Grioni, Pagona Lagiou, Saverio Caini, David S. Lopez, Heinz Freisling, Maria Dolores Chirlaque, Amanda J. Cross, Kay-Tee Khaw, Isabel Drake, Timothy J. Key, Konstantinos K. Tsilidis, Domenico Palli, Marc J. Gunter, David C. Muller, Abhijit Sen, Malene Outzen, Manuela M. Bergmann, and María José Sánchez

Subjects
Cancer Research, medicine.medical_specialty, business.industry, Proportional hazards model, Incidence (epidemiology), Hazard ratio, Cancer, medicine.disease, European Prospective Investigation into Cancer and Nutrition, 03 medical and health sciences, Prostate cancer, 0302 clinical medicine, Oncology, 030220 oncology & carcinogenesis, Internal medicine, Epidemiology, medicine, business, Cohort study
Abstract

The epidemiological evidence regarding the association of coffee and tea consumption with prostate cancer risk is inconclusive, and few cohort studies have assessed these associations by disease stage and grade. We examined the associations of coffee (total, caffeinated and decaffeinated) and tea intake with prostate cancer risk in the European Prospective Investigation into Cancer and Nutrition. Among 142,196 men, 7,036 incident prostate cancer cases were diagnosed over 14 years of follow-up. Data on coffee and tea consumption were collected through validated country-specific food questionnaires at baseline. We used Cox proportional hazards regression models to compute hazard ratios (HRs) and 95% confidence intervals (CI). Models were stratified by center and age, and adjusted for anthropometric, lifestyle and dietary factors. Median coffee and tea intake were 375 and 106 mL/day, respectively, but large variations existed by country. Comparing the highest (median of 855 mL/day) versus lowest (median of 103 mL/day) consumers of coffee and tea (450 vs. 12 mL/day) the HRs were 1.02 (95% CI, 0.94–1.09) and 0.98 (95% CI, 0.90–1.07) for risk of total prostate cancer and 0.97 (95% CI, 0.79–1.21) and 0.89 (95% CI, 0.70–1.13) for risk of fatal disease, respectively. No evidence of association was seen for consumption of total, caffeinated or decaffeinated coffee or tea and risk of total prostate cancer or cancer by stage, grade or fatality in this large cohort. Further investigations are needed to clarify whether an association exists by different preparations or by concentrations and constituents of these beverages.

Published
2018

167. Genetic determinants of telomere length and risk of pancreatic cancer: A PANDoRA study

Author

Rudolf Kaaks, Thilo Hackert, Federico Canzian, Livia Archibugi, H. Bas Bueno-de-Mesquita, Angelo Andriulli, Juozas Kupcinskas, Kai Uwe Saum, Yogesh K. Vashist, Andrea Mambrini, Kay-Tee Khaw, Andrea Szentesi, Rita T. Lawlor, Laimas Virginijus Jonaitis, Domenica Gioffreda, Raffaele Pezzilli, Katarina Cuk, Daniela Basso, Ludmila Vodickova, Claudio Pasquali, Pavel Vodicka, Oliver Strobel, Martin Lovecek, Péter Hegyi, Chiara Valsuani, Krzysztof Jamroziak, Gabriele Capurso, Renata Talar-Wojnarowska, Martina Matarazzi, Jakob R. Izbicki, Niccola Funel, Hanneke W. M. van Laarhoven, Pavel Soucek, Daniele Campa, Beatrice Mohelnikova-Duchonova, Francesca Federici, Hermann Brenner, Franco Bambi, Anna Katharina König, Carlo Federico Zambon, Verena Katzke, Maarten F. Bijlsma, William Greenhalf, Francesca Tavano, Felice Pirozzi, Gianfranco Delle Fave, Ofure Obazee, Cosimo Sperti, Jörg Kaiser, Giulia Martina Cavestro, Timothy J. Key, and Stefano Landi

Subjects
Genetics, Oncology, Cancer Research, medicine.medical_specialty, Pancreatic disease, Cancer, Single-nucleotide polymorphism, Biology, medicine.disease, 03 medical and health sciences, 0302 clinical medicine, Genetic marker, 030220 oncology & carcinogenesis, Pancreatic cancer, Internal medicine, Mendelian randomization, medicine, SNP, Risk assessment
Abstract

Telomere deregulation is a hallmark of cancer. Telomere length measured in lymphocytes (LTL) has been shown to be a risk marker for several cancers. For pancreatic ductal adenocarcinoma (PDAC) consensus is lacking whether risk is associated with long or short telomeres. Mendelian randomization approaches have shown that a score built from SNPs associated with LTL could be used as a robust risk marker. We explored this approach in a large scale study within the PANcreatic Disease ReseArch (PANDoRA) consortium. We analyzed 10 SNPs (ZNF676-rs409627, TERT-rs2736100, CTC1-rs3027234, DHX35-rs6028466, PXK-rs6772228, NAF1-rs7675998, ZNF208-rs8105767, OBFC1-rs9420907, ACYP2-rs11125529 and TERC-rs10936599) alone and combined in a LTL genetic score ("teloscore", which explains 2.2% of the telomere variability) in relation to PDAC risk in 2,374 cases and 4,326 controls. We identified several associations with PDAC risk, among which the strongest were with the TERT-rs2736100 SNP (OR = 1.54; 95%CI 1.35-1.76; p = 1.54 × 10-10 ) and a novel one with the NAF1-rs7675998 SNP (OR = 0.80; 95%CI 0.73-0.88; p = 1.87 × 10-6 , ptrend = 3.27 × 10-7 ). The association of short LTL, measured by the teloscore, with PDAC risk reached genome-wide significance (p = 2.98 × 10-9 for highest vs. lowest quintile; p = 1.82 × 10-10 as a continuous variable). In conclusion, we present a novel genome-wide candidate SNP for PDAC risk (TERT-rs2736100), a completely new signal (NAF1-rs7675998) approaching genome-wide significance and we report a strong association between the teloscore and risk of pancreatic cancer, suggesting that telomeres are a potential risk factor for pancreatic cancer.

Published
2018

168. Antibody Responses to

Author

Julia, Butt, Mazda, Jenab, Michael, Pawlita, Anne, Tjønneland, Cecilie, Kyrø, Marie-Christine, Boutron-Ruault, Franck, Carbonnel, Catherine, Dong, Rudolf, Kaaks, Tilman, Kühn, Heiner, Boeing, Matthias B, Schulze, Antonia, Trichopoulou, Anna, Karakatsani, Carlo, La Vecchia, Domenico, Palli, Claudia, Agnoli, Rosario, Tumino, Carlotta, Sacerdote, Salvatore, Panico, Bas, Bueno-de-Mesquita, Roel, Vermeulen, Inger T, Gram, Elisabete, Weiderpass, Kristin Benjaminsen, Borch, Jose Ramón, Quirós, Antonio, Agudo, Miguel, Rodríguez-Barranco, Carmen, Santiuste, Eva, Ardanaz, Bethany, Van Guelpen, Sophia, Harlid, Liher, Imaz, Aurora, Perez-Cornago, Marc J, Gunter, Semi, Zouiouich, Jin Young, Park, Elio, Riboli, Amanda J, Cross, Alicia K, Heath, Tim, Waterboer, and David J, Hughes

Subjects
Cohort Studies, Europe, Male, Helicobacter pylori, Risk Factors, Case-Control Studies, Antibody Formation, Humans, Female, Prospective Studies, Middle Aged, Colorectal Neoplasms
Abstract

WhileWe appliedFifty-one percent of colorectal cancer cases wereIn this prospective multicenter European study, antibody responses toBiological mechanisms for a potential causal role of

Published
2019

169. Lifetime and baseline alcohol intakes and risk of pancreatic cancer in the European Prospective Investigation into Cancer and Nutrition study

Author

Androniki Naska, Kim Overvad, Kuanrong Li, Eric J. Duell, Domenico Palli, Giovanna Tagliabue, Christina Bamia, Ingegerd Johansson, Petra H.M. Peeters, Nicholas J. Wareham, Anne Tjønneland, Paul Brennan, Bas Bueno-de-Mesquita, Kathryn E. Bradbury, Antonia Trichopoulou, Miguel Rodríguez-Barranco, Guri Skeie, Marie-Christine Boutron-Ruault, Salvatore Panico, Franco Berrino, Rosario Tumino, Verena Katzke, Marc J. Gunter, Sabine Naudin, Elisabete Weiderpass Vainio, Pietro Ferrari, Inger T. Gram, Anne Laure Védié, Elio Riboli, Aurelio Barricarte, Miren Dorronsoro, Nada Assi, Tristan Jaouen, José Ramón Quirós, Rudolf Kaaks, Heiner Boeing, Maria Dolores Chirlaque, Malin Sund, Hanna Sternby, Carlotta Sacerdote, Vinciane Rebours, and Cecilie Kyrø

Subjects
0301 basic medicine, Cancer Research, business.industry, Hazard ratio, Alcohol, medicine.disease, Confidence interval, European Prospective Investigation into Cancer and Nutrition, 03 medical and health sciences, chemistry.chemical_compound, 030104 developmental biology, 0302 clinical medicine, Oncology, chemistry, 030220 oncology & carcinogenesis, Pancreatic cancer, Medicine, Smoking status, business, Prospective cohort study, Wine intake, Demography
Abstract

Recent evidence suggested a weak relationship between alcohol consumption and pancreatic cancer (PC) risk. In our study, the association between lifetime and baseline alcohol intakes and the risk of PC was evaluated, including the type of alcoholic beverages and potential interaction with smoking. Within the European Prospective Investigation into Cancer and Nutrition (EPIC) study, 1,283 incident PC (57% women) were diagnosed from 476,106 cancer-free participants, followed up for 14 years. Amounts of lifetime and baseline alcohol were estimated through lifestyle and dietary questionnaires, respectively. Cox proportional hazard models with age as primary time variable were used to estimate PC hazard ratios (HR) and their 95% confidence interval (CI). Alcohol intake was positively associated with PC risk in men. Associations were mainly driven by extreme alcohol levels, with HRs comparing heavy drinkers (>60 g/day) to the reference category (0.1-4.9 g/day) equal to 1.77 (95% CI: 1.06, 2.95) and 1.63 (95% CI: 1.16, 2.29) for lifetime and baseline alcohol, respectively. Baseline alcohol intakes from beer (>40 g/day) and spirits/liquors (>10 g/day) showed HRs equal to 1.58 (95% CI: 1.07, 2.34) and 1.41 (95% CI: 1.03, 1.94), respectively, compared to the reference category (0.1-2.9 g/day). In women, HR estimates did not reach statistically significance. The alcohol and PC risk association was not modified by smoking status. Findings from a large prospective study suggest that baseline and lifetime alcohol intakes were positively associated with PC risk, with more apparent risk estimates for beer and spirits/liquors than wine intake.

Published
2018

170. Overall and Central Obesity and Risk of Lung Cancer: A Pooled Analysis

Author

Stephanie A. Smith-Warner, Shoichiro Tsugane, Mattias Johansson, Rudolf Kaaks, Rashmi Sinha, William J. Blot, Ulrike Peters, Emily White, Wei Zheng, Qing Lan, Edward Giovannucci, Xiao-Ou Shu, Charles E. Matthews, Arnulf Langhammer, Bas Bueno-de-Mesquita, Yumie Takata, Kim Robien, Danxia Yu, Yong-Bing Xiang, DeAnn Lazovich, Yu-Tang Gao, Yikyung Park, Xuehong Zhang, Walter C. Willett, Norie Sawada, and Linda M. Liao

Subjects
Adult, Male, Cancer Research, medicine.medical_specialty, Lung Neoplasms, Waist, Small-cell carcinoma, Body Mass Index, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Waist–hip ratio, Risk Factors, Internal medicine, medicine, Humans, Obesity, 030212 general & internal medicine, Lung cancer, Aged, Waist-Hip Ratio, business.industry, Hazard ratio, Cancer, Middle Aged, medicine.disease, Confidence interval, Oncology, Obesity, Abdominal, 030220 oncology & carcinogenesis, Female, Waist Circumference, business, Body mass index
Abstract

Background The obesity-lung cancer association remains controversial. Concerns over confounding by smoking and reverse causation persist. The influence of obesity type and effect modifications by race/ethnicity and tumor histology are largely unexplored. Methods We examined associations of body mass index (BMI), waist circumference (WC), and waist-hip ratio (WHR) with lung cancer risk among 1.6 million Americans, Europeans, and Asians. Cox proportional hazard regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) with adjustment for potential confounders. Analyses for WC/WHR were further adjusted for BMI. The joint effect of BMI and WC/WHR was also evaluated. Results During an average 12-year follow-up, 23 732 incident lung cancer cases were identified. While BMI was generally associated with a decreased risk, WC and WHR were associated with increased risk after controlling for BMI. These associations were seen 10 years before diagnosis in smokers and never smokers, were strongest among blacks, and varied by histological type. After excluding the first five years of follow-up, hazard ratios per 5 kg/m2 increase in BMI were 0.95 (95% CI = 0.90 to 1.00), 0.92 (95% CI = 0.89 to 0.95), and 0.89 (95% CI = 0.86 to 0.91) in never, former, and current smokers, and 0.86 (95% CI = 0.84 to 0.89), 0.94 (95% CI = 0.90 to 0.99), and 1.09 (95% CI = 1.03 to 1.15) for adenocarcinoma, squamous cell, and small cell carcinoma, respectively. Hazard ratios per 10 cm increase in WC were 1.09 (95% CI = 1.00 to 1.18), 1.12 (95% CI = 1.07 to 1.17), and 1.11 (95% CI = 1.07 to 1.16) in never, former, and current smokers, and 1.06 (95% CI = 1.01 to 1.12), 1.20 (95% CI = 1.12 to 1.29), and 1.13 (95% CI = 1.04 to 1.23) for adenocarcinoma, squamous cell, and small cell carcinoma, respectively. Participants with BMIs of less than 25 kg/m2 but high WC had a 40% higher risk (HR = 1.40, 95% CI = 1.26 to 1.56) than those with BMIs of 25 kg/m2 or greater but normal/moderate WC. Conclusions The inverse BMI-lung cancer association is not entirely due to smoking and reverse causation. Central obesity, particularly concurrent with low BMI, may help identify high-risk populations for lung cancer.

Published
2018

171. Prospective evaluation of antibody response toStreptococcus gallolyticusand risk of colorectal cancer

Author

Kathryn E. Bradbury, Carlo La Vecchia, Elisabete Weiderpass, Domenico Palli, Dagfinn Aune, Gianluca Severi, Eva Ardanaz, Michael Pawlita, Salvatore Panico, José María Huerta, H. Bas Bueno-de-Mesquita, María José Sánchez, Martina Willhauck-Fleckenstein, Anna Karakatsani, Kostas Tsilidis, Rosario Tumino, Franck Carbonnel, Marc J. Gunter, Angelika Michel, Carlotta Sacerdote, Mazda Jenab, Cecilie Kyrø, Heinz Freisling, Heiner Boeing, Claudia Agnoli, Rudolf Kaaks, Antonia Trichopoulou, Elio Riboli, Julia Butt, David J. Hughes, Tim Waterboer, Anne Tjønneland, Tilman Kühn, Catalina Bonet, Neil Murphy, and Marie-Christine Boutron-Ruault

Subjects
0301 basic medicine, Cancer Research, medicine.medical_specialty, biology, Colorectal cancer, business.industry, Case-control study, Cancer, Odds ratio, medicine.disease, Gastroenterology, Serology, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Oncology, 030220 oncology & carcinogenesis, Internal medicine, medicine, biology.protein, Streptococcus gallolyticus, Antibody, business, Prospective cohort study
Abstract

The gut microbiome is increasingly implicated in colorectal cancer (CRC) development. A subgroup of patients diagnosed with CRC show high antibody responses to Streptococcus gallolyticus subspecies gallolyticus (SGG). However, it is unclear whether the association is also present pre-diagnostically. We assessed the association of antibody responses to SGG proteins in pre-diagnostic serum samples with CRC risk in a case-control study nested within a prospective cohort. Pre-diagnostic serum samples from 485 first incident CRC cases (mean time between blood draw and diagnosis 3.4 years) and 485 matched controls in the European Prospective Investigation into Nutrition and Cancer (EPIC) study were analyzed for antibody responses to 11 SGG proteins using multiplex serology. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using multivariable conditional logistic regression models. Antibody positivity for any of the 11 SGG proteins was significantly associated with CRC risk with 56% positive controls compared to 63% positive cases (OR: 1.36, 95% CI: 1.04-1.77). Positivity for two or more proteins of a previously identified SGG 6-marker panel with greater CRC-specificity was also observed among 9% of controls compared to 17% of CRC cases, corresponding to a significantly increased CRC risk (OR: 2.17, 95% CI: 1.44-3.27). In this prospective nested case-control study, we observed a positive association between antibody responses to SGG and CRC development in serum samples taken before evident disease onset. Further work is required to establish the possibly etiological significance of these observations and whether SGG serology may be applicable for CRC risk stratification.

Published
2018

174. Body size and risk of differentiated thyroid carcinomas: Findings from the EPIC study

Author

Rinaldi, Sabina, Lise, Mauro, Clavel-Chapelon, Françoise, Boutron-Ruault, Marie-Christine, Guillas, Gwenaelle, Overvad, Kim, Tjnneland, Anne, Halkjær, Jytte, Lukanova, Annekatrin, Kaaks, Rudolf, Bergmann, Manuela M., Boeing, Heiner, Trichopoulou, Antonia, Zylis, Dimosthenis, Valanou, Elissavet, Palli, Domenico, Agnoli, Claudia, Tumino, Rosario, Polidoro, Silvia, Mattiello, Amalia, Bas Bueno-de-Mesquita, H., Peeters, Petra H., Weiderpass, Elisabete, Lund, Eiliv, Skeie, Guri, Rodríguez, Laudina, Travier, Noemie, Sánchez, Maria-José, Amiano, Pilar, Huerta, José-María, Ardanaz, Eva, Rasmuson, Torgny, Hallmans, Göran, Almquist, Martin, Manjer, Jonas, Tsilidis, Konstantinos K., Allen, Naomi E., Khaw, Kay-Tee, Wareham, Nick, Byrnes, Graham, Romieu, Isabelle, Riboli, Elio, and Franceschi, Silvia

Published
2012
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175. Dietary total antioxidant capacity and gastric cancer risk in the European prospective investigation into cancer and nutrition study

Author

Serafini, Mauro, Jakszyn, Paula, Luján-Barroso, Leila, Agudo, Antonio, Bas Bueno-de-Mesquita, H., van Duijnhoven, Fränzel J.B., Jenab, Mazda, Navarro, Carmen, Palli, Domenico, Boeing, Heiner, Wallström, Peter, Regnér, Sara, Numans, Mattijs E., Carneiro, Fatima, Boutron-Ruault, Marie-Christine, Clavel-Chapelon, Françoise, Morois, Sophie, Grioni, Sara, Panico, Salvatore, Tumino, Rosario, Sacerdote, Carlotta, Ramon Quirós, José, Molina-Montes, Esther, Huerta Castaño, Jose M., Barricarte, Aurelio, Amiano, Pilar, Khaw, Kay-Tee, Wareham, Nicholas, Allen, Naomi E., Key, Timothy J., Jeurnink, Suzanne M., Peeters, Petra H.M., Bamia, Christina, Valanou, Elisabeth, Trichopoulou, Antonia, Kaaks, Rudolf, Lukanova, Annekatrin, Bergmann, Manuela M., Lindkvist, Björn, Stenling, Roger, Johansson, Ingegerd, Dahm, Christina C., Overvad, Kim, Jensen, Majken, Olsen, Anja, Tjonneland, Anne, Lund, Eiliv, Rinaldi, Sabina, Michaud, Dominique, Mouw, Traci, Riboli, Elio, and González, Carlos A.

Published
2012
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176. The association of circulating adiponectin levels with pancreatic cancer risk: A study within the prospective EPIC cohort

Author

Grote, Verena A., Rohrmann, Sabine, Dossus, Laure, Nieters, Alexandra, Halkjær, Jytte, Tjnneland, Anne, Overvad, Kim, Stegger, Jakob, Chabbert-Buffet, Nathalie, Boutron-Ruault, Marie-Christine, Clavel-Chapelon, Françoise, Teucher, Birgit, Becker, Susen, Montonen, Jukka, Boeing, Heiner, Trichopoulou, Antonia, Lagiou, Pagona, Trichopoulos, Dimitrios, Palli, Domenico, Sieri, Sabina, Tumino, Rosario, Vineis, Paolo, Mattiello, Amalia, Argüelles, Marcial, Duell, Eric J, Molina-Montes, Esther, Larrañaga, Nerea, Chirlaque, María-Dolores, Gurrea, Aurelio Barricarte, Jeurnink, Suzanne M., Peeters, Petra HM, Ye, Weimin, Sund, Malin, Lindkvist, Björn, Johansen, Dorthe, Khaw, Kay-Tee, Wareham, Nick, Crowe, Francesca L., Romieu, Isabelle, Rinaldi, Sabina, Jenab, Mazda, Romaguera, Dora, Michaud, Dominique S., Riboli, Elio, Bas Bueno-de-Mesquita, H., and Kaaks, Rudolf

Published
2012
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177. Helicobacter pylori infection assessed by ELISA and by immunoblot and noncardia gastric cancer risk in a prospective study: the Eurgast-EPIC project

Author

González, C. A., Megraud, F., Buissonniere, A., Lujan Barroso, L., Agudo, A., Duell, E. J., Boutron-Ruault, M. C., Clavel-Chapelon, F., Palli, D., Krogh, V., Mattiello, A., Tumino, R., Sacerdote, C., Quirós, J. R., Sanchez-Cantalejo, E., Navarro, C., Barricarte, A., Dorronsoro, M., Khaw, K.-T., Wareham, N., Allen, N. E., Tsilidis, K. K., Bas Bueno-de-Mesquita, H., Jeurnink, S. M., Numans, M. E., Peeters, P. H. M., Lagiou, P., Valanou, E., Trichopoulou, A., Kaaks, R., Lukanova-McGregor, A., Bergman, M. M., Boeing, H., Manjer, J., Lindkvist, B., Stenling, R., Hallmans, G., Mortensen, L. M., Overvad, K., Olsen, A., Tjonneland, A., Bakken, K., Dumeaux, V., Lund, E., Jenab, M., Romieu, I., Michaud, D., Mouw, T., Carneiro, F., Fenge, C., and Riboli, E.

Published
2012
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178. Genome-wide association study identifies new prostate cancer susceptibility loci

Author

Schumacher, Fredrick R., Berndt, Sonja I., Siddiq, Afshan, Jacobs, Kevin B., Wang, Zhaoming, Lindstrom, Sara, Stevens, Victoria L., Chen, Constance, Mondul, Alison M., Travis, Ruth C., Stram, Daniel O., Eeles, Rosalind A., Easton, Douglas F., Giles, Graham, Hopper, John L., Neal, David E., Hamdy, Freddie C., Donovan, Jenny L., Muir, Kenneth, Al Olama, Ali Amin, Kote-Jarai, Zsofia, Guy, Michelle, Severi, Gianluca, Grönberg, Henrik, Isaacs, William B., Karlsson, Robert, Wiklund, Fredrik, Xu, Jianfeng, Allen, Naomi E., Andriole, Gerald L., Barricarte, Aurelio, Boeing, Heiner, Bas Bueno-de-Mesquita, H., Crawford, E. David, Diver, W. Ryan, Gonzalez, Carlos A., Gaziano, J. Michael, Giovannucci, Edward L., Johansson, Mattias, Le Marchand, Loic, Ma, Jing, Sieri, Sabina, Stattin, Pär, Stampfer, Meir J., Tjonneland, Anne, Vineis, Paolo, Virtamo, Jarmo, Vogel, Ulla, Weinstein, Stephanie J., Yeager, Meredith, Thun, Michael J., Kolonel, Laurence N., Henderson, Brian E., Albanes, Demetrius, Hayes, Richard B., Spencer Feigelson, Heather, Riboli, Elio, Hunter, David J., Chanock, Stephen J., Haiman, Christopher A., and Kraft, Peter

Published
2011
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179. Fluid intake and the risk of urothelial cell carcinomas in the European Prospective Investigation into Cancer and Nutrition (EPIC)

Author

Ros, Martine M., Bas Bueno-de-Mesquita, H. B., Büchner, Frederike L., Aben, Katja K.H., Kampman, Ellen, Egevad, Lars, Overvad, Kim, Tjnneland, Anne, Roswall, Nina, Clavel-Chapelon, Francoise, Kaaks, Rudolf, Chang-Claude, Jenny, Boeing, Heiner, Weikert, Steffen, Trichopoulou, Antonia, Orfanos, Philippos, Stasinopulou, Georgia, Saieva, Calogero, Krogh, Vittorio, Vineis, Paolo, Tumino, Rosario, Mattiello, Amalia, Peeters, Petra H.M., van Duijnhoven, Fränzel J.B., Lund, Eiliv, Gram, Inger T, Chirlaque, Maria D, Barricarte, Aurelio, Rodríguez, Laudina, Molina, Esther, Gonzalez, Carlos, Dorronsoro, Miren, Manjer, Jonas, Ehrnström, Roy, Ljungberg, Börje, Allen, Naomi E., Roddam, Andrew W., Khaw, Kay-Tee, Wareham, Nick, Boffetta, Paolo, Slimani, Nadia, Michaud, Dominique S., Kiemeney, Lambertus A.L.M., and Riboli, Elio

Published
2011
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180. Menopausal Hormone Therapy and Risk of Endometrial Carcinoma Among Postmenopausal Women in the European Prospective Investigation into Cancer and Nutrition

Author

Allen, Naomi E., Tsilidis, Konstantinos K., Key, Timothy J., Dossus, Laure, Kaaks, Rudolf, Lund, Eiliv, Bakken, Kjersti, Gavrilyuk, Oxana, Overvad, Kim, Tjønneland, Anne, Olsen, Anja, Fournier, Agnès, Fabre, Alban, Clavel-Chapelon, Françoise, Chabbert-Buffet, Nathalie, Sacerdote, Carlotta, Krogh, Vittorio, Bendinelli, Benedetta, Tumino, Rosario, Panico, Salvatore, Bergmann, Manuela, Schuetze, Madlen, van Duijnhoven, Fränzel J. B., Bas Bueno-de-Mesquita, H., Charlotte Onland-Moret, N., van Gils, Carla H., Amiano, Pilar, Barricarte, Aurelio, Chirlaque, Maria-Dolores, Molina-Montes, Maria-Esther, Redondo, María-Luisa, Duell, Eric J., Khaw, Kay-Tee, Wareham, Nick, Rinaldi, Sabina, Fedirko, Veronika, Mouw, Traci, Michaud, Dominique S., and Riboli, Elio

Published
2010
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181. Circulating concentrations of vitamin D in relation to pancreatic cancer risk in European populations

Author

Rosario Tumino, Jody van den Ouweland, Kathryn E. Bradbury, Petra H.M. Peeters, Martin Almquist, Fränzel J.B. Van Duijnhoven, Anja Olsen, Giuseppe Matullo, Miren Dorronsoro, Heinz Freisling, Mazda Jenab, Weimin Ye, Eivind Ness-Jensen, Elio Riboli, Maria Dolores Chirlaque, Jonas Manjer, Marina Kvaskoff, Veronika Fedirko, Verena Katzke, H. Bas Bueno-de-Mesquita, Dagfinn Aune, Marie-Christine Boutron-Ruault, Claudia Agnoli, Mireia Obón-Santacana, Frida Renström, Elisabete Weiderpass, Claire Cadeau, Teresa Norat, Cristina Lasheras, Kay-Tee Khaw, Maria Kritikou, Salvatore Panico, Henk J. van Kranen, Karina Standahl Olsen, Nicholas J. Wareham, Anouk Halfweeg, Arnulf Langhammer, María José Sánchez, Heiner Boeing, Kim Overvad, Anne Tjønneland, Domenico Palli, Antonia Trichopoulou, Ellen Kampman, Neil Murphy, Magritt Brustad, Aurelio Barricarte, Kristian Hveem, Eric J. Duell, Peter D. Siersema, Anastasia Kotanidou, and Tilman Kühn

Subjects
0301 basic medicine, Cancer Research, medicine.medical_specialty, Gastroenterology, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Internal medicine, medicine, 25-Hydroxyvitamin D 2, Vitamin D and neurology, Prospective cohort study, 2. Zero hunger, business.industry, Case-control study, 3. Good health, European Prospective Investigation into Cancer and Nutrition, 030104 developmental biology, Endocrinology, Oncology, chemistry, 030220 oncology & carcinogenesis, Nested case-control study, Calcifediol, business, Body mass index
Abstract

Evidence from in vivo, in vitro and ecological studies are suggestive of a protective effect of vitamin D against pancreatic cancer (PC). However, this has not been confirmed by analytical epidemiological studies. We aimed to examine the association between pre-diagnostic circulating vitamin D concentrations and PC incidence in European populations. We conducted a pooled nested case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC) and the Nord-Trondelag Health Study's second survey (HUNT2) cohorts. In total, 738 primary incident PC cases (EPIC n = 626; HUNT2 n = 112; median follow-up = 6.9 years) were matched to 738 controls. Vitamin D [25(OH)D2 and 25(OH)D3 combined] concentrations were determined using isotope-dilution liquid chromatography-tandem mass spectrometry. Conditional logistic regression models with adjustments for body mass index and smoking habits were used to estimate incidence rate ratios (IRRs) and 95% confidence intervals (95%CI). Compared with a reference category of >50 to 75 nmol/L vitamin D, the IRRs (95% CIs) were 0.71 (0.42-1.20); 0.94 (0.72-1.22); 1.12 (0.82-1.53) and 1.26 (0.79-2.01) for clinically pre-defined categories of ≤25; >25 to 50; >75 to 100; and >100 nmol/L vitamin D, respectively (p for trend = 0.09). Corresponding analyses by quintiles of season-standardized vitamin D concentrations also did not reveal associations with PC risk (p for trend = 0.23). Although these findings among participants from the largest combination of European cohort studies to date show increasing effect estimates of PC risk with increasing pre-diagnostic concentrations of vitamin D, they are not statistically significant.

Published
2017

182. Do pancreatic cancer and chronic pancreatitis share the same genetic risk factors? A PANcreatic Disease ReseArch (PANDoRA) consortium investigation

Author

Domenica Gioffreda, Yasuhiro Shimizu, Serena Stigliano, Hidemi Ito, Kay-Tee Khaw, Carlo Lombardo, Martin Oliverius, Ioannis Papaconstantinou, Irena Valantiene, Pavel Soucek, Claudio Pasquali, Kazuo Hara, Verena Katzke, Federico Canzian, Hendrik Strothmann, Andrea Mambrini, Paola Fogar, Gabriele Capurso, Raffaele Pezzilli, Katarina Cuk, Anna Latiano, Olivier R. Busch, Chiara Valsuani, Katja Butterbach, Oliver Strobel, Jakob R. Izbicki, Pavel Vodicka, Thilo Hackert, William Greenhalf, Cosimo Sperti, Anna Katharina König, Angelo Andriulli, Francesca Tavano, Petra H.M. Peeters, Renata Talar-Wojnarowska, Willem Niesen, Giulia Martina Cavestro, Keitaro Matsuo, Beatrice Mohelnikova-Duchonova, Frederike Dijk, Yogesh K. Vashist, Stefano Landi, Maurizio Cantore, Hermann Brenner, Roberto Valente, Daniele Campa, Manuela Pastore, H. Bas Bueno-de-Mesquita, Carlo Federico Zambon, Roberto Salvia, Milena Di Leo, Maria Gazouli, Theron Johnson, Ewa Małecka-Panas, Timothy J. Key, Peter Macinga, Rudolf Kaaks, and Juozas Kupcinskas

Subjects
0301 basic medicine, Oncology, Cancer Research, medicine.medical_specialty, Pancreatic disease, endocrine system diseases, business.industry, Case-control study, Context (language use), medicine.disease, Bioinformatics, digestive system diseases, Minor allele frequency, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, 030220 oncology & carcinogenesis, Pancreatic cancer, Internal medicine, medicine, Genetic predisposition, Pancreatitis, chronic, Risk factor, business
Abstract

Pancreatic ductal adenocarcinoma (PDAC) is a very aggressive tumor with a five-year survival of less than 6%. Chronic pancreatitis (CP), an inflammatory process in of the pancreas, is a strong risk factor for PDAC. Several genetic polymorphisms have been discovered as susceptibility loci for both CP and PDAC. Since CP and PDAC share a consistent number of epidemiologic risk factors, the aim of this study was to investigate whether specific CP risk loci also contribute to PDAC susceptibility. We selected five common SNPs (rs11988997, rs379742, rs10273639, rs2995271 and rs12688220) that were identified as susceptibility markers for CP and analyzed them in 2,914 PDAC cases, 356 CP cases and 5,596 controls retrospectively collected in the context of the international PANDoRA consortium. We found a weak association between the minor allele of the PRSS1-PRSS2-rs10273639 and an increased risk of developing PDAC (ORhomozygous = 1.19, 95% CI 1.02-1.38, p = 0.023). Additionally all the SNPs confirmed statistically significant associations with risk of developing CP, the strongest being PRSS1-PRSS2-rs10273639 (ORheterozygous = 0.51, 95% CI 0.39-0.67, p = 1.10 × 10-6 ) and MORC4-rs 12837024 (ORhomozygous = 2.07 (1.55-2.77, ptrend = 0.7 × 10-11 ). Taken together, the results from our study do not support variants rs11988997, rs379742, rs10273639, rs2995271 and rs12688220 as strong predictors of PDAC risk, but further support the role of these SNPs in CP susceptibility. Our study suggests that CP and PDAC probably do not share genetic susceptibility, at least in terms of high frequency variants.

Published
2017

183. Alcohol consumption and risk of urothelial cell bladder cancer in the European prospective investigation into cancer and nutrition cohort

Author

Anette Hjartåker, Tilman Kühn, Aurora Perez-Cornago, Pamela Ferrari, Fredrik Liedberg, L. Börje, Salvatore Panico, Emily Sonestedt, Valeria Pala, Magdalena Stepien, Kim Overvad, Margareta Johansson, Antonia Trichopoulou, José María Huerta, Elisabete Weiderpass, H. Bas Bueno-de-Mesquita, Laura Trijsburg, C. La Vecchia, Anne Tjønneland, Anna Karakatsani, María José Sánchez, Inger T. Gram, N. Roswall, Rosario Tumino, Edoardo Botteri, and Renée T. Fortner

Subjects
0301 basic medicine, Gynecology, Cancer Research, medicine.medical_specialty, Bladder cancer, Proportional hazards model, business.industry, Hazard ratio, Confounding, medicine.disease, Confidence interval, 3. Good health, European Prospective Investigation into Cancer and Nutrition, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Oncology, 030220 oncology & carcinogenesis, Internal medicine, Cohort, medicine, business, Cohort study
Abstract

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 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.

Published
2017

184. Consumption of fruits, vegetables and fruit juices and differentiated thyroid carcinoma risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) study

Author

Nicholas J. Wareham, Petra H.M. Peeters, Isabel Drake, Martin Almquist, Elena Salamanca-Fernández, Marie-Christine Boutron-Ruault, Kay Thee Khaw, Anne Kirstine Eriksen, Antonio Agudo, Sara Grioni, Elisavet Valanou, Julie A. Schmidt, Isabelle Romieu, Fabrice Bonnet, Rosario Tumino, Augustin Scalbert, Dagfinn Aune, Anne Tjønneland, Pilar Amiano, H. Bas Bueno-de-Mesquita, Heiner Boeing, Christine L. Parr, Anna Karakatsani, Susana Merino, Verena Katzke, Elio Riboli, Virginie Béraud, Aurélie Affret, Konstantinos K. Tsilidis, Guri Skeie, Kim Overvad, Maria Sandström, Giovanna Masala, Aurora Perez-Cornago, Fulvio Ricceri, Raul Zamora-Ros, Maria Dolores Chirlaque, Silvia Franceschi, Valerie Cayssials, Tilman Kühn, Joakim Hennings, Nadia Slimani, Elisabete Weiderpass, Sabina Rinaldi, Antonia Trichopoulou, Eva Ardanaz, and Maria Santucci de Magistris

Subjects
Cancer Research, business.industry, Fruits vegetables, Fruit juice intake, European Prospective Investigation into Cancer and Nutrition, Thyroid carcinoma, 03 medical and health sciences, 0302 clinical medicine, Oncology, 030220 oncology & carcinogenesis, Medicine, Epic study, High sugar, 030212 general & internal medicine, Food science, business, Prospective cohort study, Cohort study
Abstract

Fruit and vegetable (FV 95% CI: 0.68-1.15; p-trend = 0.44), vegetables (HR: 0.89; 95% CI: 0.69-1.14; p-trend = 0.56), or fruit (HR: 1.00; 95% CI: 0.79-1.26; p-trend = 0.64). No significant association was observed with any individual type of vegetable or fruit. However, there was a positive borderline trend with fruit juice intake (HR: 1.23; 95% CI: 0.98-1.53; p-trend = 0.06). This study did not find any significant association between FV however a positive trend with fruit juice intake was observed, possibly related to its high sugar content.

Published
2017

185. Hepcidin levels and gastric cancer risk in the EPIC-EurGast study

Author

Núria Aranda, Bodil Ohlsson, Francesca Fasanelli, Heiner Boeing, Antonio Agudo, Ana Fonseca-Nunes, Fulvio Ricceri, Rosario Tumino, Domenico Palli, Aurora Perez-Cornago, Mazda Jenab, Petra H.M. Peeters, Elisabete Weiderpass, Emilio Sánchez-Cantalejo, José María Huerta, Leila Lujan-Barroso, Rudolf Kaaks, Miren Dorronsoro, H. Bas Bueno-de-Mesquita, Monica Tous, Tilman Kühn, Anja Olsen, Kim Overvad, Kay-Tee Khaw, José Maria Quirós, Klas Sjöberg, Amanda J. Cross, Marc J. Gunter, Antonia Trichopoulou, Vittorio Krogh, Anne Tjønneland, Aurelio Barricarte, Effie Vasilopoulou, Eleni Peppa, Amalia Mattiello, Victoria Arija, and Paula Jakszyn

Subjects
0301 basic medicine, Cancer Research, medicine.medical_specialty, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Hepcidin, hemic and lymphatic diseases, Internal medicine, medicine, Stomach cancer, biology, business.industry, Stomach, Confounding, nutritional and metabolic diseases, Cancer, Odds ratio, medicine.disease, European Prospective Investigation into Cancer and Nutrition, Ferritin, 030104 developmental biology, Endocrinology, medicine.anatomical_structure, Oncology, 030220 oncology & carcinogenesis, biology.protein, business
Abstract

Hepcidin is the main regulator of iron homeostasis and dysregulation of proteins involved in iron metabolism has been associated with tumorogenesis. However, to date, no epidemiological study has researched the association between hepcidin levels and gastric cancer risk. To further investigate the relationship between hepcidin levels and gastric cancer risk, we conducted a nested case-control study (EURGAST) within the multicentric European Prospective Investigation into Cancer and Nutrition study. The study included 456 primary incident gastric adenocarcinoma cases and 900 matched controls that occurred during an average of 11 years of follow-up. We measured serum levels of hepcidin-25, iron, ferritin, transferrin and C-reactive protein. Odds ratios (ORs) and 95% confidence intervals (CIs) for the risk of gastric cancer by hepcidin levels were estimated from multivariable conditional logistic regression models. Mediation effect of the ferritin levels on the hepcidin-gastric cancer pathway was also evaluated. After adjusting for relevant confounders, we observed a statistically significant inverse association between gastric cancer and hepcidin levels (OR 5 ng/l = 0.96, 95% CI = 0.93–0.99). No differences were found by tumor localization or histological type. In mediation analysis, we found that the direct effect of hepcidin only represents a nonsignificant 38% (95% CI: −69%, 91%). In summary, these data suggest that the inverse association of hepcidin levels and gastric cancer risk was mostly accounted by ferritin levels. Further investigation including repeated measures of hepcidin is needed to clarify their role in gastric carcinogenesis.

Published
2017

186. Plasma microRNAs as biomarkers of pancreatic cancer risk in a prospective cohort study

Author

Nicholas J. Wareham, Giovanna Tagliabue, Paul Brennan, Salvatore Panico, Miguel Rodríguez-Barranco, Giuseppe Matullo, Alessio Naccarati, Stuart Sherman, Line Moi, Paolo Vineis, María Dolores Chirlaque, Marc J. Gunter, Pagona Lagiou, Rudolf Kaaks, Antonia Trichopoulou, David C. Muller, Verena Katzke, Gianluca Severi, Eva Ardanaz, Ghislaine Scelo, Vinciane Rebours, Murray Korc, H. Bas Bueno-de-Mesquita, Lill-Tove Busund, Elisabete Weiderpass, Samantha Deitz McElyea, Eric J. Duell, Rosario Tumino, Petra H.M. Peeters, Greg Cote, Marie-Christine Boutron-Ruault, Anne Tjønneland, José Ramón Quirós, Anastasia Kotanidou, Núria Sala, Dagfinn Aune, Anja Olsen, Ruth C. Travis, Kim Overvad, Domenico Palli, Leila Lujan-Barroso, Kay-Tee Khaw, Miren Dorronsoro, and Heiner Boeing

Subjects
0301 basic medicine, Oncology, Cancer Research, medicine.medical_specialty, Pathology, Receiver operating characteristic, business.industry, Case-control study, Cancer, medicine.disease, Logistic regression, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, 030220 oncology & carcinogenesis, Pancreatic cancer, Internal medicine, Cohort, medicine, business, Prospective cohort study, Cohort study
Abstract

Noninvasive biomarkers for early pancreatic ductal adenocarcinoma (PDAC) diagnosis and disease risk stratification are greatly needed. We conducted a nested case-control study within the Prospective Investigation into Cancer and Nutrition (EPIC) cohort to evaluate prediagnostic microRNAs (miRs) as biomarkers of subsequent PDAC risk. A panel of eight miRs (miR-10a, -10b, -21-3p, -21-5p, -30c, -106b, -155 and -212) based on previous evidence from our group was evaluated in 225 microscopically confirmed PDAC cases and 225 controls matched on center, sex, fasting status and age/date/time of blood collection. MiR levels in prediagnostic plasma samples were determined by quantitative RT-PCR. Logistic regression was used to model levels and PDAC risk, adjusting for covariates and to estimate area under the receiver operating characteristic curves (AUC). Plasma miR-10b, -21-5p, -30c and -106b levels were significantly higher in cases diagnosed within 2 years of blood collection compared to matched controls (all p-values

Published
2017

187. Coffee, tea and melanoma risk: findings from the European Prospective Investigation into Cancer and Nutrition

Author

Emily Sonestedt, Marc J. Gunter, Karin Jirström, Inge Huybrechts, Antonia Trichopoulou, Tilman Kühn, Neil Murphy, Rudolf Kaaks, Petra H.M. Peeters, Giovanna Tagliabue, Elisabete Weiderpass, Isabelle Savoye, Calogero Saieva, H. Bas Bueno-de-Mesquita, Oskar Hemmingsson, Elisavet Valanou, Marie-Christine Boutron-Ruault, Kristina E.N. Petersen, Reza Ghiasvand, Kim Overvad, Maria Kritikou, Salvatore Panico, Marko Lukic, Lena Maria Nilsson, Eva Ardanaz, Saverio Caini, Nerea Larrañaga, Bodil Hammer Bech, Marina Kvaskoff, Domenico Palli, Anne Tjønneland, Kay-Tee Khaw, Ingrid Ljuslinder, Marit B. Veierød, Nicholas J. Wareham, Raul Zamora-Ros, Francesca Mancini, Maria Dolores Chirlaque, Heiner Boeing, Elena Salamanca Fernández, Carlotta Sacerdote, Timothy J. Key, Iris Cervenka, Rosario Tumino, Anna Floegel, Konstantinos K. Tsilidis, José Ramón Quirós, and Giovanna Masala

Subjects
0301 basic medicine, Cancer Research, medicine.medical_specialty, business.industry, Hazard ratio, Surgery, European Prospective Investigation into Cancer and Nutrition, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Oncology, Quartile, 030220 oncology & carcinogenesis, Environmental health, Epidemiology, Cutaneous melanoma, medicine, business, Risk assessment, Prospective cohort study, Cohort study
Abstract

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.

Published
2017

188. Endometrial cancer risk prediction including serum-based biomarkers: results from the EPIC cohort

Author

Kim Overvad, Marc J. Gunter, Inger T. Gram, Giovanna Masala, Agnès Fournier, Salma Butt, Kay-Tee Khaw, J. Ramón Quirós, Sabina Rinaldi, Carlotta Sacerdote, Tilman Kühn, José María Huerta, Meric Konar, H. Bas Bueno-de-Mesquita, Gianluca Severi, Renée T. Fortner, Eva Ardanaz, Leila Lujan-Barroso, Claudia Agnoli, Vasiliki Benetou, Rosario Tumino, Amalia Mattiello, Anika Hüsing, Oxana Gavrilyuk, Marie-Christine Boutron-Ruault, Elio Riboli, Antonia Trichopoulou, Rudolf Kaaks, Nerea Larrañaga, Petra H.M. Peeters, Eva Lundin, Emilio Sánchez-Cantalejo, Elisabete Weiderpass, Louise Hansen, Signe Borgquist, Ioanna Tzoulaki, Philippos Orfanos, Naomi E. Allen, Annika Idahl, Melissa A. Merritt, Anne Tjønneland, Laure Dossus, and Heiner Boeing

Subjects
0301 basic medicine, Gynecology, Oncology, Cancer Research, medicine.medical_specialty, Adiponectin, business.industry, Endometrial cancer, Absolute risk reduction, Adipokine, medicine.disease, 3. Good health, European Prospective Investigation into Cancer and Nutrition, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, 030220 oncology & carcinogenesis, Internal medicine, Cohort, medicine, Biomarker (medicine), 10. No inequality, business, Prospective cohort study
Abstract

Endometrial cancer risk prediction models including lifestyle, anthropometric and reproductive factors have limited discrimination. Adding biomarker data to these models may improve predictive capacity; to our knowledge, this has not been investigated for endometrial cancer. Using a nested case–control study within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, we investigated the improvement in discrimination gained by adding serum biomarker concentrations to risk estimates derived from an existing risk prediction model based on epidemiologic factors. Serum concentrations of sex steroid hormones, metabolic markers, growth factors, adipokines and cytokines were evaluated in a step-wise backward selection process; biomarkers were retained at p

Published
2017

189. Biomarkers of folate and vitamin B12 and breast cancer risk: report from the EPIC cohort

Author

R. Tumino, Marco Matejcic, J. R. Quirós, Anne Zeleniuch-Jacquotte, Marc J. Gunter, Björn Gylling, Elisabete Weiderpass, Pagona Lagiou, Genevieve Buckland, Salvatore Panico, Flavie Perrier, C. Ricci, Renée T. Fortner, Fulvio Ricceri, Pilar Amiano, Inge Huybrechts, Veronique Chajes, Mathilde His, Claire Cadeau, Petra H.M. Peeters, Isabelle Romieu, M-D Chirlaque, Timothy J. Key, Vassiliki Benetou, Antonia Trichopoulou, David G. Cox, Elio Riboli, M. C. Boutron-Ruault, Rudolf Kaaks, Sabina Sieri, D. Palli, María José Sánchez, Aurelio Barricarte, Carine Biessy, H. Bas Bueno-de-Mesquita, J. D. De Batlle, H. Boeing, C. H. van Gils, and Guri Skeie

Subjects
0301 basic medicine, Oncology, Gynecology, Cancer Research, medicine.medical_specialty, business.industry, Follow up studies, Case-control study, EPIC, medicine.disease, 03 medical and health sciences, B vitamins, 030104 developmental biology, 0302 clinical medicine, Breast cancer, 030220 oncology & carcinogenesis, Internal medicine, Epidemiology, Cohort, medicine, Vitamin B12, business
Abstract

Epidemiological studies have reported inconsistent findings for the association between B vitamins and breast cancer (BC) risk. We investigated the relationship between biomarkers of folate and vit ...

Published
2017

190. Outdoor air pollution and risk for kidney parenchyma cancer in 14 European cohorts

Author

Johan Nilsson Sommar, Anne Tjønneland, Petra H.M. Peeters, Paolo Vineis, Nancy L. Pedersen, Ingeborg M. Kooter, Marloes Eeftens, Carlotta Sacerdote, Alessandro Marcon, Marie Pedersen, Claudia Galassi, Massimo Stafoggia, Andrea Jaensch, Enrica Migliore, Kirsten Thorup Eriksen, Andrei Pyko, Rob Beelen, Laura Fratiglioni, Ranjeet S. Sokhi, Bertil Forsberg, Gerard Hoek, Ming-Yi Tsai, Fulvio Ricceri, Miren Dorronsoro, Gunn Marit Aasvang, H. Bas Bueno-de-Mesquita, Meng Wang, Bernhard Föger, Zorana Jovanovic Andersen, Ulf de Faire, Kees de Hoogh, Gudrun Weinmayr, Sara Grioni, Mette Sørensen, Claes-Göran Östenson, Roel Vermeulen, Pilar Amiano, Ibon Tamayo, Michelle Plusquin, Norun Hjertager Krog, Göran Pershagen, Timothy J. Key, David Olsson, Gabriele Nagel, Bert Brunekreef, Ole Raaschou-Nielsen, Michal Korek, Vittorio Krogh, and Bente Oftedal

Subjects
Pollutant, Cancer Research, business.industry, Air pollution, Cancer, Environmental exposure, 010501 environmental sciences, Particulates, medicine.disease, medicine.disease_cause, complex mixtures, 01 natural sciences, 03 medical and health sciences, 0302 clinical medicine, Oncology, 030220 oncology & carcinogenesis, Environmental health, Parenchyma, medicine, business, Risk assessment, Kidney cancer, 0105 earth and related environmental sciences
Abstract

Several studies have indicated weakly increased risk for kidney cancer among occupational groups exposed to gasoline vapors, engine exhaust, polycyclic aromatic hydrocarbons and other air pollutant ...

Published
2017

191. White cell counts in relation to mortality in a general population of cohort study in the Netherlands : A mediating effect or not?

Author

Itziar Abete, Yunxia Lu, Monique Verschuren, Camille Lassale, Yvonne T. van der Schouw, and Bas Bueno-de-Mesquita

Subjects
Male, obesity, Epidemiology, Cardiovascular, Body Mass Index, Leukocyte Count, 0302 clinical medicine, Risk Factors, Surveys and Questionnaires, Risk of mortality, Medicine, 030212 general & internal medicine, Longitudinal Studies, Prospective Studies, Body mass index, Cancer, Netherlands, Original Research, Medicine(all), education.field_of_study, Smoking, General Medicine, Middle Aged, 030220 oncology & carcinogenesis, Cohort, Public Health and Health Services, Female, Cohort study, Adult, medicine.medical_specialty, Multivariate cox regression models, Population, Clinical Trials and Supportive Activities, Clinical Sciences, White cell count (WCC), smoking, 03 medical and health sciences, Young Adult, Clinical Research, Internal medicine, Journal Article, Humans, mediation, education, Nutrition, Aged, Proportional Hazards Models, Other Medical and Health Sciences, white cell count, business.industry, Proportional hazards model, Prevention, medicine.disease, Obesity, mortality, Good Health and Well Being, Case-Control Studies, business
Abstract

BackgroundWhite cell count (WCC) is a clinical marker of inflammation. Data are limited regarding the association of total and differential WCC with risk of mortality, and its role related with smoking and body mass index (BMI).MethodsA total of 14 433 participants (4150 men; 10 283 women; average age 47.3±11.8 years) from the Dutch European Prospective Investigation into Cancer and Nutrition-Netherlands cohort were included. The associations between prediagnostic total WCC and its subtypes and risk of all-cause, cancer and cardiovascular disease (CVD) mortality were assessed. The role of WCC related with smoking and BMI on mortality was further explored. Multivariate Cox regression models were performed to estimate the HR and 95% CI.ResultsAfter an average follow-up of 15.8 years, a total of 936 death cases were identified (466 cancer; 179 CVD; 291 other causes). Statistically significant graded associations between total WCC, and counts of lymphocytes, monocytes, neutrophils and eosinophils and risk of total mortality were observed. These associations were more apparent in current smokers. Strong associations for all-cause mortality or cancer mortality were observed in subjects with BMI ≥25 kg/m2, ever smoking and elevated WCC (HR 3.92, 95% CI 2.76 to 5.57; HR 3.93, 95% CI 2.30 to 6.72). WCC partly mediated the associations between smoking or BMI and all-cause mortality.ConclusionsPrediagnostic WCC and its subtypes are associated with all-cause, cancer and CVD mortality risk. It may play a partially mediate role on the association between smoking or obesity and mortality.

Published
2019

192. A nutrient-wide association study for risk of prostate cancer in the European Prospective Investigation into Cancer and Nutrition and the Netherlands Cohort Study

Author

Kim Overvad, Rosario Tumino, Isabel Drake, Pietro Ferrari, Anna Karakatsani, Fulvio Ricceri, Antonio Agudo, Piet A. van den Brandt, Milan Geybels, María José Sánchez, Paolo Vineis, Tilman Kühn, Timothy J. Key, Aurelio Barricarte Gurrea, Chirag J. Patel, Georgia Martimianaki, Elio Riboli, Bas Bueno-de-Mesquita, David S. Lopez, Nerea Larrañaga, Marc J. Gunter, David C. Muller, Vittorio Krogh, Kay-Tee Khaw, José Ramón Quirós, Domenico Palli, Antonia Trichopoulou, Ioanna Tzoulaki, Nikos Papadimitriou, Renée T. Fortner, Pär Stattin, Elisabete Weiderpass, Carmen Santiuste, Ingegerd Johansson, Konstantinos K. Tsilidis, Anne Tjønneland, Heiner Boeing, Dorthe Furstrand Lauritzen, Anders Bjartell, Aurora Perez-Cornago, Elin Thysell, World Cancer Research Fund International, Epidemiologie, RS: GROW - R1 - Prevention, RS: CAPHRI - R5 - Optimising Patient Care, Tsilidis, Konstantinos K [0000-0002-8452-8472], Apollo - University of Cambridge Repository, and Tsilidis, Konstantinos K. [0000-0002-8452-8472]

Subjects
Male, Oncology, Epidemiology, Medicine (miscellaneous), Cohort Studies, Prostate cancer, 0302 clinical medicine, Risk Factors, Medicine, Prospective Studies, 030212 general & internal medicine, INDEX, Netherlands, Nutrition and Dietetics, Hazard ratio, Original Contribution, European Prospective Investigation into Cancer and Nutrition, Europe, Näringslära, 030220 oncology & carcinogenesis, Cohort, Cohort study, Life Sciences & Biomedicine, medicine.medical_specialty, Diet, Nutrition, QUESTIONNAIRE, OVARIAN-CANCER, CALCIUM, DIET, 03 medical and health sciences, SDG 3 - Good Health and Well-being, Internal medicine, CARBOHYDRATE, Humans, Science & Technology, Nutrition & Dietetics, business.industry, SCALE PROSPECTIVE COHORT, Prostatic Neoplasms, Nutrients, medicine.disease, Confidence interval, PRODUCTS, PHYSICAL-ACTIVITY, 1111 Nutrition and Dietetics, business, Body mass index, Genome-Wide Association Study
Abstract

Funder: Centre International de Recherche sur le Cancer; doi: http://dx.doi.org/10.13039/100008700, Purpose: The evidence from the literature regarding the association of dietary factors and risk of prostate cancer is inconclusive. Methods: A nutrient-wide association study was conducted to systematically and comprehensively evaluate the associations between 92 foods or nutrients and risk of prostate cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC). Cox proportional hazard regression models adjusted for total energy intake, smoking status, body mass index, physical activity, diabetes and education were used to estimate hazard ratios and 95% confidence intervals for standardized dietary intakes. As in genome-wide association studies, correction for multiple comparisons was applied using the false discovery rate (FDR < 5%) method and suggested results were replicated in an independent cohort, the Netherlands Cohort Study (NLCS). Results: A total of 5916 and 3842 incident cases of prostate cancer were diagnosed during a mean follow-up of 14 and 20 years in EPIC and NLCS, respectively. None of the dietary factors was associated with the risk of total prostate cancer in EPIC (minimum FDR-corrected P, 0.37). Null associations were also observed by disease stage, grade and fatality, except for positive associations observed for intake of dry cakes/biscuits with low-grade and butter with aggressive prostate cancer, respectively, out of which the intake of dry cakes/biscuits was replicated in the NLCS. Conclusions: Our findings provide little support for an association for the majority of the 92 examined dietary factors and risk of prostate cancer. The association of dry cakes/biscuits with low-grade prostate cancer warrants further replication given the scarcity in the literature.

Published
2019

193. Association of Dietary Fiber and Yogurt Consumption With Lung Cancer Risk: A Pooled Analysis

Author

Danxia Yu, Yong-Bing Xiang, Xiao-Ou Shu, De Ann Lazovich, Yikyung Park, Elio Riboli, Guri Skeie, Stephanie A. Smith-Warner, Ingegerd Johansson, Qing Lan, Anne Tjønneland, Mattias Johansson, Rosario Tumino, Xuehong Zhang, Emily White, Rashmi Sinha, Kim Robien, William J. Blot, Wei Zheng, J. Ramón Quirós, Yumie Takata, Bas Bueno-de-Mesquita, Yu-Tang Gao, and Jae Jeong Yang

Subjects
Cancer Research, medicine.medical_specialty, business.industry, Proportional hazards model, Hazard ratio, Cancer, medicine.disease, Small-cell carcinoma, Confidence interval, 03 medical and health sciences, 0302 clinical medicine, Oncology, 030220 oncology & carcinogenesis, Internal medicine, Cohort, medicine, Adenocarcinoma, 030212 general & internal medicine, business, Lung cancer, Original Investigation
Abstract

Importance Dietary fiber (the main source of prebiotics) and yogurt (a probiotic food) confer various health benefits via modulating the gut microbiota and metabolic pathways. However, their associations with lung cancer risk have not been well investigated. Objective To evaluate the individual and joint associations of dietary fiber and yogurt consumption with lung cancer risk and to assess the potential effect modification of the associations by lifestyle and other dietary factors. Design, Setting, and Participants This pooled analysis included 10 prospective cohorts involving 1 445 850 adults from studies that were conducted in the United States, Europe, and Asia. Data analyses were performed between November 2017 and February 2019. Using harmonized individual participant data, hazard ratios and 95% confidence intervals for lung cancer risk associated with dietary fiber and yogurt intakes were estimated for each cohort by Cox regression and pooled using random-effects meta-analysis. Participants who had a history of cancer at enrollment or developed any cancer, died, or were lost to follow-up within 2 years after enrollment were excluded. Exposures Dietary fiber intake and yogurt consumption measured by validated instruments. Main Outcomes and Measures Incident lung cancer, subclassified by histologic type (eg, adenocarcinoma, squamous cell carcinoma, and small cell carcinoma). Results The analytic sample included 627 988 men, with a mean (SD) age of 57.9 (9.0) years, and 817 862 women, with a mean (SD) age of 54.8 (9.7) years. During a median follow-up of 8.6 years, 18 822 incident lung cancer cases were documented. Both fiber and yogurt intakes were inversely associated with lung cancer risk after adjustment for status and pack-years of smoking and other lung cancer risk factors: hazard ratio, 0.83 (95% CI, 0.76-0.91) for the highest vs lowest quintile of fiber intake; and hazard ratio, 0.81 (95% CI, 0.76-0.87) for high vs no yogurt consumption. The fiber or yogurt associations with lung cancer were significant in never smokers and were consistently observed across sex, race/ethnicity, and tumor histologic type. When considered jointly, high yogurt consumption with the highest quintile of fiber intake showed more than 30% reduced risk of lung cancer than nonyogurt consumption with the lowest quintile of fiber intake (hazard ratio, 0.67 [95% CI, 0.61-0.73] in total study populations; hazard ratio 0.69 [95% CI, 0.54-0.89] in never smokers), suggesting potential synergism. Conclusions and Relevance Dietary fiber and yogurt consumption was associated with reduced risk of lung cancer after adjusting for known risk factors and among never smokers. Our findings suggest a potential protective role of prebiotics and probiotics against lung carcinogenesis.

Published
2019

194. Association of circulating Vitamin D with colorectal cancer depends on Vitamin D-binding protein isoforms: A pooled, nested, case-control study

Author

W. Dana Flanders, Tilman Kühn, Anne Tjønneland, Kana Wu, Roberd M. Bostick, Yahya Mahamat-Saleh, Marjorie L. McCullough, Aurelio Barricarte Gurrea, Konstantinos K. Tsilidis, Antonia Trichopoulou, Johan Hultdin, Bas Bueno-de-Mesquita, Mingyang Song, Elisabete Weiderpass, Edward Giovannucci, David C. Gibbs, Magritt Brustad, Marc J. Gunter, Veronika Fedirko, Mazda Jenab, Aurora Perez-Cornago, Caroline Y. Um, Centre International de Recherche contre le Cancer - International Agency for Research on Cancer (CIRC - IARC), Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), and Institut Gustave Roussy (IGR)

Subjects
Vitamin, 25-HYDROXYVITAMIN D, D SUPPLEMENTATION, Cancer Research, medicine.medical_specialty, Vitamin D-binding protein, [SDV]Life Sciences [q-bio], Lower risk, Gastroenterology, CALCIUM, Article, vitamin D deficiency, SERUM, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, D-RECEPTOR, GENETIC-VARIANTS, GC-GLOBULIN, Internal medicine, Vitamin D and neurology, Medicine, GENOME-WIDE ASSOCIATION, 030304 developmental biology, RISK, 0303 health sciences, Cancer och onkologi, Science & Technology, VDP::Medisinske Fag: 700::Helsefag: 800::Samfunnsmedisin, sosialmedisin: 801, business.industry, Odds ratio, medicine.disease, PREVENTION, Confidence interval, 3. Good health, Oncology, chemistry, 030220 oncology & carcinogenesis, Cancer and Oncology, Nested case-control study, VDP::Medical disciplines: 700::Health sciences: 800::Community medicine, Social medicine: 801, business, Life Sciences & Biomedicine
Abstract

Background Higher circulating 25-hydroxyvitamin-D [25(OH)D] concentrations are consistently inversely associated with colorectal cancer (CRC) risk in observational studies. However, it is unknown whether this association depends on the functional GC-rs4588*A (Thr436Lys) variant encoding the vitamin D–binding protein-2 (DBP2) isoform, which may affect vitamin D status and bioavailability. Methods We analyzed data from 1710 incident CRC cases and 1649 incidence-density–matched controls nested within three prospective cohorts of mostly Caucasians. Study-specific incidence rate ratios (RRs) for associations of prediagnostic, season-standardized 25(OH)D concentrations according to DBP2 isoform with CRC were estimated using multivariable unconditional logistic regression and were pooled using fixed-effects models. All statistical significance tests were two-sided. Results The odds of having 25(OH)D concentrations less than 50 nmol/L (considered insufficient by the Institute of Medicine) were 43% higher for each DBP2-encoding variant (rs4588*A) inherited (per DBP2 odds ratio [OR] = 1.43, 95% confidence interval [CI] = 1.27 to 1.62, Ptrend = 1.2 × 10−8). The association of 25(OH)D concentrations with CRC risk differed by DBP2: 25(OH)D concentrations considered sufficient (≥ 50 nmol/L), relative to deficient ( Conclusions Our results suggest that the 25(OH)D-CRC association may differ by DBP isoform, and those with a DBP2-encoding genotype linked to vitamin D insufficiency may particularly benefit from adequate 25(OH)D for CRC prevention.

Published
2019

195. Gallstones and incident colorectal cancer in a large pan-European cohort study

Author

Anne Tjønneland, Kim Overvad, Giovanna Masala, Marc J. Gunter, Antonia Trichopoulou, Raul Zamora-Ros, Heather Ward, Pagona Lagiou, Susana Merino, Elisabete Weiderpass, Marie-Christine Boutron-Ruault, Heinz Freisling, Rosario Tumino, Aurelio Barricarte, Dagfinn Aune, Carla H. van Gils, Gianluca Severi, Elom K. Aglago, Roel Vermeulen, Heiner Boeing, Hanna Nyström, Bas Bueno-de-Mesquita, Franck Carbonnel, Rudolf Kaaks, Amanda J. Cross, María Dolores Chirlaque, Neil Murphy, Mazda Jenab, Elio Riboli, Tilman Kühn, Martin Rutegård, Aurora Perez-Cornago, Christina Bamia, Michael F. Leitzmann, Miguel Rodríguez-Barranco, Sara Grioni, Miren Dorronsoro, Amalia Mattiello, Anja Olsen, Carlotta Sacerdote, Imperial College Trust, One Health Chemisch, and dIRAS RA-2

Subjects
Adult, Male, medicine.medical_specialty, Cancer Research, CHOLECYSTECTOMY, Population, colorectal cancer, Gallstones, DISEASE, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Internal medicine, Journal Article, Medicine, Humans, 1112 Oncology and Carcinogenesis, Registries, Oncology & Carcinogenesis, Risk factor, education, Prospective cohort study, POPULATION, Proportional Hazards Models, RISK, education.field_of_study, Science & Technology, business.industry, Incidence, Hazard ratio, ASSOCIATION, cohort, Middle Aged, medicine.disease, European Prospective Investigation into Cancer and Nutrition, Europe, Oncology, 030220 oncology & carcinogenesis, Cohort, SERUM BILIRUBIN, Female, business, Colorectal Neoplasms, EPIC, Life Sciences & Biomedicine, Cohort study
Abstract

Gallstones, a common gastrointestinal condition, can lead to several digestive complications and can result in inflammation. Risk factors for gallstones include obesity, diabetes, smoking and physical inactivity, all of which are known risk factors for colorectal cancer (CRC), as is inflammation. However, it is unclear whether gallstones are a risk factor for CRC. We examined the association between history of gallstones and CRC in the European Prospective Investigation into Cancer and Nutrition (EPIC) study, a prospective cohort of over half a million participants from ten European countries. History of gallstones was assessed at baseline using a self-reported questionnaire. The analytic cohort included 334,986 participants; a history of gallstones was reported by 3,917 men and 19,836 women, and incident CRC was diagnosed among 1,832 men and 2,178 women (mean follow-up: 13.6 years). Hazard ratios (HR) and 95% confidence intervals (CI) for the association between gallstones and CRC were estimated using Cox proportional hazards regression models, stratified by sex, study centre, and age at recruitment. The models were adjusted for body mass index, diabetes, alcohol intake, and physical activity. A positive, marginally significant association was detected between gallstones and CRC among women in multivariable analyses (HR=1.14, 95%CI 0.99-1.31, p=0.077). The relationship between gallstones and CRC among men was inverse but not significant (HR=0.81, 95%CI 0.63-1.04, p=0.10). Additional adjustment for details of reproductive history or waist circumference yielded minimal changes to the observed associations. Further research is required to confirm the nature of the association between gallstones and CRC by sex. This article is protected by copyright. All rights reserved.

Published
2019

196. Association between soft drink consumption and mortality in 10 European countries

Author

Pilar Amiano, Jonathan Pearson-Stuttard, María José Sánchez, Kay-Tee Khaw, Roel Vermeulen, Marc J. Gunter, Krasimira Aleksandrova, J. Ramón Quirós, Heiner Boeing, Rudolf Kaaks, Stina Ramne, Antonia Trichopoulou, W M Monique Verschuren, Elio Riboli, Eva Ardanaz, David C. Muller, Elisabete Weiderpass, Vivian Viallon, Bas Bueno-de-Mesquita, Antonio Agudo, Anna Karakatsani, Jytte Halkjær, Kim Overvad, Anne Tjønneland, Tammy Y.N. Tong, Heinz Freisling, Jolanda M. A. Boer, Emily Sonestedt, Tilman Kühn, Georgia Martimianaki, Neil Murphy, Christine L. Parr, Guri Skeie, Domenico Palli, Pernilla Lif Holgersson, Magdalena Stepien, Guy Fagherazzi, Bethany Van Guelpen, Francesca Mancini, Alicia K Heath, Konstantinos K. Tsilidis, Marie-Christine Boutron-Ruault, Salvatore Panico, Lluís Cirera, Amy Mullee, Claudia Agnoli, Julie A. Schmidt, Dora Romaguera, Rosario Tumino, and Carlotta Sacerdote

Subjects
medicine.medical_specialty, Population, Mortalities, 01 natural sciences, Begudes, Beverages, 03 medical and health sciences, 0302 clinical medicine, Artificial sweetenings, Environmental health, Journal Article, Mortalitat, Internal Medicine, Medicine, VDP::Medisinske Fag: 700, Sugar sweetenings, 030212 general & internal medicine, Mortality, 0101 mathematics, education, Consumption (economics), education.field_of_study, business.industry, Public health, 010102 general mathematics, Hazard ratio, European Prospective Investigation into Cancer and Nutrition, Europe, VDP::Medical disciplines: 700, Soft drink consumption, Cohort, Europa, business, Cohort study
Abstract

Importance: Soft drinks are frequently consumed, but whether this consumption is associated with mortality risk is unknown and has been understudied in European populations to date. Objective: To examine the association between total, sugar-sweetened, and artificially sweetened soft drink consumption and subsequent total and cause-specific mortality. Design, Setting, and Participants: This population-based cohort study involved participants (n = 451 743 of the full cohort) in the European Prospective Investigation into Cancer and Nutrition (EPIC), an ongoing, large multinational cohort of people from 10 European countries (Denmark, France, Germany, Greece, Italy, the Netherlands, Norway, Spain, Sweden, and the United Kingdom), with participants recruited between January 1, 1992, and December 31, 2000. Excluded participants were those who reported cancer, heart disease, stroke, or diabetes at baseline; those with implausible dietary intake data; and those with missing soft drink consumption or follow-up information. Data analyses were performed from February 1, 2018, to October 1, 2018. Exposure: Consumption of total, sugar-sweetened, and artificially sweetened soft drinks. Main Outcomes and Measures Total mortality and cause-specific mortality. Hazard ratios (HRs) and 95% CIs were estimated using multivariable Cox proportional hazards regression models adjusted for other mortality risk factors. Results: In total, 521 330 individuals were enrolled. Of this total, 451 743 (86.7%) were included in the study, with a mean (SD) age of 50.8 (9.8) years and with 321 081 women (71.1%). During a mean (range) follow-up of 16.4 (11.1 in Greece to 19.2 in France) years, 41 693 deaths occurred. Higher all-cause mortality was found among participants who consumed 2 or more glasses per day (vs consumers of

Published
2019

197. Prediagnostic Plasma Bile Acid Levels and Colon Cancer Risk: A Prospective Study

Author

Domenico Palli, Mazda Jenab, Susana Merino, Elio Riboli, Aurelio Barricarte, Salvatore Panico, Heinz Freisling, Aurora Perez-Cornago, Agustín Lahoz, Francesca Mancini, Alicia K Heath, Augustin Scalbert, Maria J. Sánchez, Carlotta Sacerdote, Carla H. van Gils, Sandra González Maldonado, Solomon A Sowah, Sandra Colorado-Yohar, Marta Roca, Magdalena Stepien, Kay-Tee Khaw, Paula Jakszyn, Paschalis Thriskos, Tilman Kühn, Neil Murphy, Marc J. Gunter, Disorn Sookthai, Claudia Agnoli, Marina Lopez-Nogueroles, Gianluca Severi, Marie-Christine Boutron-Ruault, Antonia Trichopoulou, Sabina Rinaldi, Anika Hüsing, Anna Karakatsani, Bas Bueno-de-Mesquita, Amanda J. Cross, Heiner Boeing, Theron Johnson, Rudolf Kaaks, Antje Damms-Machado, Julie A. Schmidt, Rosario Tumino, and Veronika Fedirko

Subjects
Male, Cancer Research, diagnosis, Gastroenterology, Cohort Studies, chemistry.chemical_compound, taurodeoxycholic acid, 0302 clinical medicine, metabolites, 0303 health sciences, Bile acid, Articles, Middle Aged, European Prospective Investigation into Cancer and Nutrition, colon cancer, Oncology, Glycodeoxycholic acid, glycocholic acid, 030220 oncology & carcinogenesis, Colonic Neoplasms, Female, Taurodeoxycholic acid, Corrigendum, carcinogenesis, Adult, Risk, medicine.medical_specialty, medicine.drug_class, Glycocholic acid, Taurochenodeoxycholic acid, colorectal cancer, taurocholic acid, digestive system, Bile Acids and Salts, 03 medical and health sciences, nutrition in cancer, glycochenodeoxycholic acid, Internal medicine, tandem mass spectrometry, taurochenodeoxycholic acid, medicine, Glycochenodeoxycholic acid, Journal Article, Humans, 1112 Oncology and Carcinogenesis, Oncology & Carcinogenesis, plasma, 030304 developmental biology, Aged, bile acids, glycodeoxycholic acid, colon, business.industry, Taurocholic acid, digestive system diseases, chemistry, Spain, Case-Control Studies, business
Abstract

Background Bile acids have been proposed to promote colon carcinogenesis. However, there are limited prospective data on circulating bile acid levels and colon cancer risk in humans. Methods Associations between prediagnostic plasma levels of 17 primary, secondary, and tertiary bile acid metabolites (conjugated and unconjugated) and colon cancer risk were evaluated in a nested case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Bile acid levels were quantified by tandem mass spectrometry in samples from 569 incident colon cancer cases and 569 matched controls. Multivariable logistic regression analyses were used to estimate odds ratios (ORs) for colon cancer risk across quartiles of bile acid concentrations. Results Positive associations were observed between colon cancer risk and plasma levels of seven conjugated bile acid metabolites: the primary bile acids glycocholic acid (ORquartile 4 vs quartile 1= 2.22, 95% confidence interval [CI] = 1.52 to 3.26), taurocholic acid (OR = 1.78, 95% CI = 1.23 to 2.58), glycochenodeoxycholic acid (OR = 1.68, 95% CI = 1.13 to 2.48), taurochenodeoxycholic acid (OR = 1.62, 95% CI = 1.11 to 2.36), and glycohyocholic acid (OR = 1.65, 95% CI = 1.13 to 2.40), and the secondary bile acids glycodeoxycholic acid (OR = 1.68, 95% CI = 1.12 to 2.54) and taurodeoxycholic acid (OR = 1.54, 95% CI = 1.02 to 2.31). By contrast, unconjugated bile acids and tertiary bile acids were not associated with risk. Conclusions This prospective study showed that prediagnostic levels of certain conjugated primary and secondary bile acids were positively associated with risk of colon cancer. Our findings support experimental data to suggest that a high bile acid load is colon cancer promotive.

Published
2019

198. Vitamin D-Related Genes, Blood Vitamin D Levels and Colorectal Cancer Risk in Western European Populations

Author

Aleksandrova Krasimira, Hannah B. Mandle, Sophia Harlid, Alicia K Heath, Konstantinos K. Tsilidis, Dimitris Thanos, Wanzhe Zhu, Elisabete Weiderpass, Dagfinn Aune, Anne Tjønneland, Björn Gylling, Mazda Jenab, Marie-Christine Boutron-Ruault, Heinz Freisling, Guri Skeie, Sandra Colorado-Yohar, Pilar Amiano, Aurora Perez-Cornago, María José Sánchez, Theron Johnson, Marc J. Gunter, Bas Bueno-de-Mesquita, Veronika Fedirko, Vittorio Krogh, Ramón Quirós, Pietro Ferrari, Carlotta Sacerdote, Elio Riboli, Isabelle Romieu, Afshan Siddiq, Peter D. Siersema, Neil Murphy, Vittorio Perduca, Antonia Trichopoulou, Franck Carbonnel, Aurelio Barricarte, Fränzel J.B. Van Duijnhoven, Anja Olsen, Periklis Makrythanasis, David J. Hughes, Tilman Kühn, Salvatore Panico, Núria Sala, International Agency for Cancer Research (IACR), Department of Epidemiology and Biostatistics, Imperial College London-Faculty of Medicine-School of public health, The University of Hong Kong (HKU)-The University of Hong Kong (HKU), Nutrition and Metabolism Section, International Agency for Research on Cancer, Centre International de Recherche contre le Cancer (CIRC), School of Public Health [London, UK] (Faculty of Medicine), Imperial College London, Department for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment [Bilthoven] (RIVM), Danish Cancer Society, Danish Cancer Society Research Center, Mathématiques Appliquées Paris 5 (MAP5 - UMR 8145), Université Paris Descartes - Paris 5 (UPD5)-Institut National des Sciences Mathématiques et de leurs Interactions (INSMI)-Centre National de la Recherche Scientifique (CNRS), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Centre de recherche en épidémiologie et santé des populations (CESP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Division of Cancer Epidemiology, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Deutsches Krebsforschungszentrum, WHO Collaborating Center for Nutrition and Health, Unit of Nutritional Epidemiology and Nutrition in Public Health, Dept of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School [Athens]-University of Athens Medical School [Athens], University of Geneva, Department of Clinical and Experimental Medicine, Università degli studi di Napoli Federico II, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), CPO Piemonte, Department of Community Medicine, Faculty of Health Sciences, The Arctic University of Norway (UiT), Catalan Institute of Oncology, CIBER de Epidemiología y Salud Pública (CIBERESP), Andalusian School of Public Health [Granada], Nuffield Department of Population Health - Cancer Epidemiology Unit, University of Oxford [Oxford], and School of Public Health - Department of Epidemiology and Biostatistics

Subjects
0301 basic medicine, Male, Nutrition and Disease, Colorectal cancer, vitamin D, Calcitriol receptor, chemistry.chemical_compound, Tumours of the digestive tract Radboud Institute for Health Sciences [Radboudumc 14], 0302 clinical medicine, Polymorphism (computer science), Risk Factors, Transforming Growth Factor beta, Voeding en Ziekte, Nutritional Physiological Phenomena, Prospective Studies, Vitamin D, ComputingMilieux_MISCELLANEOUS, Nutrition and Dietetics, Incidence, Middle Aged, 3. Good health, European Prospective Investigation into Cancer and Nutrition, Näringslära, Europe, 030220 oncology & carcinogenesis, Female, lcsh:Nutrition. Foods and food supply, Signal Transduction, Vitamin, medicine.medical_specialty, Vitamina D, lcsh:TX341-641, [SDV.CAN]Life Sciences [q-bio]/Cancer, Single-nucleotide polymorphism, Biology, Polymorphism, Single Nucleotide, Article, Colorectal neoplasms, 03 medical and health sciences, single nucleotide polymorphism (SNP), Càncer colorectal, Single nucleotide polymorphism (SNP), Internal medicine, medicine, Vitamin D and neurology, Humans, VDP::Medisinske Fag: 700, Genetic Predisposition to Disease, Aged, Cancer och onkologi, colorectal neoplasms, medicine.disease, VDP::Medical disciplines: 700, 030104 developmental biology, Endocrinology, chemistry, Cancer and Oncology, Case-Control Studies, incidence, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Calcifediol, Food Science
Abstract

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

Published
2019

199. Heterogeneity of Colorectal Cancer Risk Factors by Anatomical Subsite in 10 European Countries: A Multinational Cohort Study

Author

Christina C. Dahm, Carlo La Vecchia, Domenico Palli, Salvatore Panico, Nicholas J. Wareham, Amanda J. Cross, Aurelio Barricarte, Jonna Berntsson, Elisabete Weiderpass, Rudolf Kaaks, Mazda Jenab, Anna Karakatsani, Franck Carbonnel, Xiaonan Xue, Heather Ward, Kristin Benjaminsen Borch, Elio Riboli, Marc J. Gunter, Kay-Tee Khaw, Kathryn E. Bradbury, Tilman Kühn, Marina Kvaskoff, Robin Myte, Antonia Trichopoulou, J. Ramón Quirós, Rosario Tumino, Bas Bueno-de-Mesquita, Kim Overvad, Cecilie Kyrø, Sara Grioni, José María Huerta, Francesca Fasanelli, Karin Jirström, Björn Gylling, Leire Gil, Guri Skeie, Neil Murphy, Paula Jakszyn, Marie-Christine Boutron-Ruault, María José Sánchez, Heiner Boeing, Anne Tjønneland, Krasimira Aleksandrova, Petra H.M. Peeters, Joseph A. Rothwell, Wareham, Nicholas [0000-0003-1422-2993], Apollo - University of Cambridge Repository, Murphy, Neil, Ward, Heather A, Jenab, Mazda, Rothwell, Joseph A, Boutron-Ruault, Marie-Christine, Carbonnel, Franck, Kvaskoff, Marina, Kaaks, Rudolf, Kühn, Tilman, Boeing, Heiner, Aleksandrova, Krasimira, Weiderpass, Elisabete, Skeie, Guri, Borch, Kristin Benjaminsen, Tjønneland, Anne, Kyrø, Cecilie, Overvad, Kim, Dahm, Christina C, Jakszyn, Paula, Sánchez, Maria-Jose, Gil, Leire, Huerta, José M, Barricarte, Aurelio, Quirós, J Ramón, Khaw, Kay-Tee, Wareham, Nick, Bradbury, Kathryn E, Trichopoulou, Antonia, La Vecchia, Carlo, Karakatsani, Anna, Palli, Domenico, Grioni, Sara, Tumino, Rosario, Fasanelli, Francesca, Panico, Salvatore, Bueno-de-Mesquita, Ba, Peeters, Petra H, Gylling, Björn, Myte, Robin, Jirström, Karin, Berntsson, Jonna, Xue, Xiaonan, Riboli, Elio, Cross, Amanda J, Gunter, Marc J, Department of Medical and Clinical Genetics, Faculty of Medicine, and Imperial College Trust

Subjects
Oncology, Male, Risk Factors, Colorectal cancer, EPIC, Anatomic Subsite, HEIGHT, 0302 clinical medicine, Prospective Studies, 2. Zero hunger, Incidence, Hazard ratio, Smoking, Gastroenterology, Colonoscopy, Proximal Colon, Middle Aged, C-REACTIVE PROTEIN, TIME, 3. Good health, European Prospective Investigation into Cancer and Nutrition, Europe, Multinational corporation, 030220 oncology & carcinogenesis, 030211 gastroenterology & hepatology, Female, Menopausal hormone therapy, Colorectal Neoplasms, Life Sciences & Biomedicine, Cohort study, Adult, medicine.medical_specialty, Alcohol Drinking, Colon, 3122 Cancers, anatomical subsite, Gastroenterology and Hepatology, 03 medical and health sciences, Internal medicine, REGRESSION, Journal Article, medicine, Gastroenterologi, Humans, VDP::Medisinske Fag: 700, Distal Colon, Exercise, Life Style, RECTAL-CANCER, METAANALYSIS, Colorectal Cancer, Cancer och onkologi, Science & Technology, Gastroenterology & Hepatology, Hepatology, business.industry, Risk Factor, Rectum, Cancer, 1103 Clinical Sciences, medicine.disease, VDP::Medical disciplines: 700, PHYSICAL-ACTIVITY, 3121 General medicine, internal medicine and other clinical medicine, Cancer and Oncology, Heterogeneity, business, Follow-Up Studies
Abstract

Background & Aims - Colorectal cancer located at different anatomical subsites may have distinct etiologies and risk factors. Previous studies that have examined this hypothesis have yielded inconsistent results, possibly because most studies have been of insufficient size to identify heterogeneous associations with precision. Methods - In the European Prospective Investigation into Cancer and Nutrition study, we used multivariable joint Cox proportional hazards models, which accounted for tumors at different anatomical sites (proximal colon, distal colon, and rectum) as competing risks, to examine the relationships between 14 established/suspected lifestyle, anthropometric, and reproductive/menstrual risk factors with colorectal cancer risk. Heterogeneity across sites was tested using Wald tests. Results - After a median of 14.9 years of follow-up of 521,330 men and women, 6291 colorectal cancer cases occurred. Physical activity was related inversely to proximal colon and distal colon cancer, but not to rectal cancer (P heterogeneity = .03). Height was associated positively with proximal and distal colon cancer only, but not rectal cancer (P heterogeneity = .0001). For men, but not women, heterogeneous relationships were observed for body mass index (P heterogeneity = .008) and waist circumference (P heterogeneity = .03), with weaker positive associations found for rectal cancer, compared with proximal and distal colon cancer. Current smoking was associated with a greater risk of rectal and proximal colon cancer, but not distal colon cancer (P heterogeneity = .05). No heterogeneity by anatomical site was found for alcohol consumption, diabetes, nonsteroidal anti-inflammatory drug use, and reproductive/menstrual factors. Conclusions - The relationships between physical activity, anthropometry, and smoking with colorectal cancer risk differed by subsite, supporting the hypothesis that tumors in different anatomical regions may have distinct etiologies.

Published
2019

200. KIM-1 as a blood-based marker for early detection of kidney cancer: a prospective nested case–control study

Author

Roel Vermeulen, Prateek Khanna, David C. Muller, Paolo Vineis, Antonio Agudo, Heiner Boeing, Rupal S. Bhatt, Elio Riboli, Joseph V. Bonventre, Domenico Palli, Amanda J. Cross, Antonia Trichopoulou, H. Bas Bueno-de-Mesquita, Maria Dolores Chirlaque, Kim Overvad, Timothy J. Key, Therese Haugdahl Nøst, Anna Karakatsani, Sabina Sieri, Ghislaine Scelo, Paul Brennan, Konstantinos K. Tsilidis, Torkjel M. Sandanger, Elisabete Weiderpass, Mattias Johansson, Salvatore Panico, J. Ramón Quirós, Gianluca Severi, Marina Kvaskoff, Venkata S. Sabbisetti, Vittorio Perduca, Miguel Rodríguez-Barranco, Carlo La Vecchia, Petra H.M. Peeters, Unit of Nutrition and Cancer, International Agency for Cancer Research (IACR), Centre for Environment and Health, Imperial College London-School of public health, The University of Hong Kong (HKU)-The University of Hong Kong (HKU), Unit of Environment Cancer Epidemiology, IARC, Danish Cancer Society Research Center, Division of Environmental Epidemiology, Institute for Risk Assessment Sciences, Section of Epidemiology, Aarhus University [Aarhus], National Institute for Public Health and the Environment [Bilthoven] (RIVM), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Mathématiques Appliquées Paris 5 (MAP5 - UMR 8145), Université Paris Descartes - Paris 5 (UPD5)-Institut National des Sciences Mathématiques et de leurs Interactions (INSMI)-Centre National de la Recherche Scientifique (CNRS), Nutrition, hormones et cancer: épidémiologie et prévention (E3N), Epidémiologie, sciences sociales, santé publique (IFR 69), Université Panthéon-Sorbonne (UP1)-Université Paris-Sud - Paris 11 (UP11)-École des hautes études en sciences sociales (EHESS)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Panthéon-Sorbonne (UP1)-Université Paris-Sud - Paris 11 (UP11)-École des hautes études en sciences sociales (EHESS)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Mode de vie, génétique et santé : études intégratives et transgénérationnelles (U1018 (Équipe 9)), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Gustave Roussy (IGR), Istituto Mario Negri and Universita di Milano, Istituto Mario Negri and Università di Milano, Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute (ISPO), Nutritional Epidemiology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Department of Clinical and Experimental Medicine, Università degli studi di Napoli Federico II, Genetic Epidemiology Group [Helsinki], Folkhälsan Research Center, Faculty of Medecine [Helsinki], University of Helsinki-University of Helsinki-Faculty of Medecine [Helsinki], University of Helsinki-University of Helsinki, Unit of Nutrition, Environment and Cancer, Institut d'Investigació Biomèdica de Bellvitge [Barcelone] (IDIBELL), Consorcio de Investigación Biomédica en Red especializado en Epidemiología y Salud Pública (CIBERESP), Los Centros de Investigación Biomédica en Red (CIBER), Cancer Epidemiology Unit, University of Oxford [Oxford], Harvard Medical School [Boston] (HMS), Cancer Research UK, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Université Paris 1 Panthéon-Sorbonne (UP1)-Université Paris-Sud - Paris 11 (UP11)-École des hautes études en sciences sociales (EHESS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris 1 Panthéon-Sorbonne (UP1)-Université Paris-Sud - Paris 11 (UP11)-École des hautes études en sciences sociales (EHESS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Gustave Roussy (IGR)-Université Paris-Sud - Paris 11 (UP11), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut Gustave Roussy (IGR), One Health Chemisch, dIRAS RA-2, Scelo, Ghislaine, Muller, David C, Riboli, Elio, Johansson, Mattia, Cross, Amanda J, Vineis, Paolo, Tsilidis, Konstantinos K, Brennan, Paul, Boeing, Heiner, Peeters, Petra H M, Vermeulen, Roel C H, Overvad, Kim, Bueno-de-Mesquita, H Ba, Severi, Gianluca, Perduca, Vittorio, Kvaskoff, Marina, Trichopoulou, Antonia, La Vecchia, Carlo, Karakatsani, Anna, Palli, Domenico, Sieri, Sabina, Panico, Salvatore, Weiderpass, Elisabete, Sandanger, Torkjel M, Nøst, Therese H, Agudo, Antonio, Quirós, J Ramón, Rodríguez-Barranco, Miguel, Chirlaque, Maria-Dolore, Key, Timothy J, Khanna, Prateek, Bonventre, Joseph V, Sabbisetti, Venkata S, and Bhatt, Rupal S

Subjects
BIOMARKER, Oncology, Male, Cancer Research, 030232 urology & nephrology, urologic and male genital diseases, Rate ratio, 0302 clinical medicine, Renal cell carcinoma, Hepatitis A Virus Cellular Receptor 1, Prospective cohort study, ComputingMilieux_MISCELLANEOUS, Early Detection of Cancer, 2. Zero hunger, education.field_of_study, Incidence (epidemiology), Prognosis, female genital diseases and pregnancy complications, Kidney Neoplasms, 3. Good health, 030220 oncology & carcinogenesis, Cohort, Female, Life Sciences & Biomedicine, INJURY MOLECULE-1, medicine.medical_specialty, Population, [SDV.CAN]Life Sciences [q-bio]/Cancer, Article, 03 medical and health sciences, Internal medicine, medicine, Biomarkers, Tumor, Humans, 1112 Oncology and Carcinogenesis, Oncology & Carcinogenesis, education, neoplasms, Carcinoma, Renal Cell, Survival analysis, Neoplasm Staging, Science & Technology, business.industry, medicine.disease, ROC Curve, Case-Control Studies, Nested case-control study, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, Follow-Up Studies
Abstract

Purpose: Renal cell carcinoma (RCC) has the potential for cure with surgery when diagnosed at an early stage. Kidney injury molecule-1 (KIM-1) has been shown to be elevated in the plasma of RCC patients. We aimed to test whether plasma KIM-1 could represent a means of detecting RCC prior to clinical diagnosis. Experimental Design: KIM-1 concentrations were measured in prediagnostic plasma from 190 RCC cases and 190 controls nested within a population-based prospective cohort study. Cases had entered the cohort up to 5 years before diagnosis, and controls were matched on cases for date of birth, date at blood donation, sex, and country. We applied conditional logistic regression and flexible parametric survival models to evaluate the association between plasma KIM-1 concentrations and RCC risk and survival. Results: The incidence rate ratio (IRR) of RCC for a doubling in KIM-1 concentration was 1.71 [95% confidence interval (CI), 1.44–2.03, P = 4.1 × 10−23], corresponding to an IRR of 63.3 (95% CI, 16.2–246.9) comparing the 80th to the 20th percentiles of the KIM-1 distribution in this sample. Compared with a risk model including known risk factors of RCC (age, sex, country, body mass index, and tobacco smoking status), a risk model additionally including KIM-1 substantially improved discrimination between cases and controls (area under the receiver-operating characteristic curve of 0.8 compared with 0.7). High plasma KIM-1 concentrations were also associated with poorer survival (P = 0.0053). Conclusions: Plasma KIM-1 concentrations could predict RCC incidence up to 5 years prior to diagnosis and were associated with poorer survival. Clin Cancer Res; 24(22); 5594–601. ©2018 AACR.

Published
2019

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