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A Prospective Diet-Wide Association Study for Risk of Colorectal Cancer in EPIC.

Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece; International Agency for Research on Cancer, Lyon, France. Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece. Department of Epidemiology, GROW School for Oncology and Developmental Biology, Care and Public Health Research Institute, Maastricht University, Maastricht, Netherlands. Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom. Biomedical Research Foundation of the Academy of Athens, Athens, Greece. International Agency for Research on Cancer, Lyon, France. Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbrücke, Bergholz-Rehbrücke, Germany. U1018, Nutrition, Hormones and Women's Health Team, Centre for Research in Epidemiology and Population Health, Inserm, Villejuif, France. University of Hawai'i Cancer Center, Honolulu, Hawaii. Department of Preventive Medicine and Population Health, University of Texas Medical Branch School of Medicine, Galveston, Texas; Division of Urology, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, Texas. German Institute of Human Nutrition Potsdam-Rehbrücke, Bergholz-Rehbrücke, Germany. Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom. Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany; Institute of Nutrition Science, University of Potsdam, Nuthetal, Germany. Department of Community Medicine, Faculty of Health Sciences, University of Tromsø-The Arctic University of Norway, Tromsø, Norway. Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. Diet, Genes and Environment, Danish Cancer Society Research Center, Copenhagen, Denmark. Department of Radiation Sciences-Oncology, Umeå University, Umeå, Sweden. Department of Odontology, Umeå University, Umeå, Sweden. Department of Clinical and Biological Sciences, University of Turin, Turin, Italy; Unit of Epidemiology, Regional Health Service ASL TO3, Grugliasco, Italy. Department of Clinical Sciences in Malmö, Lund University, Malmö, Sweden. Murcia Regional Health Council, IMIB-Arrixaca, Murcia, Spain; CIBER of Epidemiology and Public Health, Instituto de Salud Carlos III, Madrid, Spain. Department of Public Health, Aarhus University, Aarhus, Denmark. Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. CIBER of Epidemiology and Public Health, Instituto de Salud Carlos III, Madrid, Spain; Public Health Division of Gipuzkoa, Biodonostia Research Institute, San Sebastián, Spain. Diet, Genes and Environment, Danish Cancer Society Research Center, Copenhagen, Denmark; Department of Public Health, University of Copenhagen, Copenhagen, Denmark. Instituto de Salud Pública de Navarra, Pamplona, Spain. Department for Determinants of Chronic Diseases, National Institute for Public Health and the Environment, Bilthoven, the Netherlands. CIBER of Epidemiology and Public Health, Instituto de Salud Carlos III, Madrid, Spain; Instituto de Salud Pública de Navarra, Pamplona, Spain; Navarra Institute for Health Research (IdiSNA), Pamplona, Spain. Oncology and Pathology, Department of Clinical Sciences Lund, Lund University, Lund, Sweden. CIBER of Epidemiology and Public Health, Instituto de Salud Carlos III, Madrid, Spain; Escuela Andaluza de Salud Pública, Granada, Spain; Instituto de Investigación Biosanitaria (ibs.GRANADA), Granada, Spain; Department of Preventive Medicine and Public Health, University of Granada, Granada, Spain. Cancer Registry and Histopathology Department, Provincial Health Authority, Ragusa, Italy. Dipartimento di Medicina Clinica e Chirurgia, University of Naples Federico II, Naples, Italy. Unit of Nutrition and Cancer, Cancer Epidemiology Research Programme, Catalan Institute of Oncology, Barcelona, Spain; Blanquerna School of Health Sciences, Ramon Llull University, Barcelona, Spain. Cancer Risk Factors and Life-Style Epidemiology Unit, Institute for Cancer Research, Prevention and Clinical Network, Florence, Italy. Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands. Public Health Directorate, Asturias, Spain. CESP UMR1018, Gustave Roussy, Équipe "Exposome et Hérédité," Inserm-UVSQ, Université Paris-Saclay, Villejuif, France; Department of Statistics, Computer Science and Applications, University of Florence, Florence, Italy. Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece; Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom. Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece; Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom. Electronic address: k.tsilidis@imperial.ac.uk.

Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 2022;(4):864-873.e13
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Abstract

BACKGROUND & AIMS Evidence regarding the association of dietary exposures with colorectal cancer (CRC) risk is not consistent with a few exceptions. Therefore, we conducted a diet-wide association study (DWAS) in the European Prospective Investigation into Cancer and Nutrition (EPIC) to evaluate the associations between several dietary exposures with CRC risk. METHODS The association of 92 food and nutrient intakes with CRC risk was assessed in 386,792 participants, 5069 of whom developed incident CRC. Correction for multiple comparisons was performed using the false discovery rate, and emerging associations were examined in the Netherlands Cohort Study (NLCS). Multiplicative gene-nutrient interactions were also tested in EPIC based on known CRC-associated loci. RESULTS In EPIC, alcohol, liquor/spirits, wine, beer/cider, soft drinks, and pork were positively associated with CRC, whereas milk, cheese, calcium, phosphorus, magnesium, potassium, riboflavin, vitamin B6, beta carotene, fruit, fiber, nonwhite bread, banana, and total protein intakes were inversely associated. Of these 20 associations, 13 were replicated in the NLCS, for which a meta-analysis was performed, namely alcohol (summary hazard ratio [HR] per 1-SD increment in intake: 1.07; 95% confidence interval [CI], 1.04-1.09), liquor/spirits (HR per 1-SD increment in intake, 1.04; 95% CI, 1.02-1.06), wine (HR per 1-SD increment in intake, 1.04; 95% CI, 1.02-1.07), beer/cider (HR per 1-SD increment in intake, 1.06; 95% CI, 1.04-1.08), milk (HR per 1-SD increment in intake, 0.95; 95% CI, 0.93-0.98), cheese (HR per 1-SD increment in intake, 0.96; 95% CI, 0.94-0.99), calcium (HR per 1-SD increment in intake, 0.93; 95% CI, 0.90-0.95), phosphorus (HR per 1-SD increment in intake, 0.92; 95% CI, 0.90-0.95), magnesium (HR per 1-SD increment in intake, 0.95; 95% CI, 0.92-0.98), potassium (HR per 1-SD increment in intake, 0.96; 95% CI, 0.94-0.99), riboflavin (HR per 1-SD increment in intake, 0.94; 95% CI, 0.92-0.97), beta carotene (HR per 1-SD increment in intake, 0.96; 95% CI, 0.93-0.98), and total protein (HR per 1-SD increment in intake, 0.94; 95% CI, 0.92-0.97). None of the gene-nutrient interactions were significant after adjustment for multiple comparisons. CONCLUSIONS Our findings confirm a positive association for alcohol and an inverse association for dairy products and calcium with CRC risk, and also suggest a lower risk at higher dietary intakes of phosphorus, magnesium, potassium, riboflavin, beta carotene, and total protein.

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Publication Type : Meta-Analysis

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