Elom K Aglago1, Inge Huybrechts2, Neil Murphy2, Corinne Casagrande2, Genevieve Nicolas2, Tobias Pischon3, Veronika Fedirko4, Gianluca Severi5, Marie-Christine Boutron-Ruault5, Agnès Fournier5, Verena Katzke6, Tilman Kühn6, Anja Olsen7, Anne Tjønneland8, Christina C Dahm9, Kim Overvad10, Cristina Lasheras11, Antonio Agudo12, Maria-Jose Sánchez13, Pilar Amiano14, José Maria Huerta15, Eva Ardanaz16, Aurora Perez-Cornago17, Antonia Trichopoulou18, Anna Karakatsani19, Georgia Martimianaki20, Domenico Palli21, Valeria Pala22, Rosario Tumino23, Alessio Naccarati24, Salvatore Panico25, Bas Bueno-de-Mesquita26, Anne May27, Jeroen W G Derksen27, Sophie Hellstrand28, Bodil Ohlsson29, Maria Wennberg30, Bethany Van Guelpen31, Guri Skeie32, Magritt Brustad32, Elisabete Weiderpass33, Amanda J Cross34, Heather Ward34, Elio Riboli34, Teresa Norat34, Veronique Chajes2, Marc J Gunter2. 1. Nutrition and Metabolism Section, International Agency for Research on Cancer (IARC), Lyon, France. Electronic address: aglagoe@fellows.iarc.fr. 2. Nutrition and Metabolism Section, International Agency for Research on Cancer (IARC), Lyon, France. 3. Molecular Epidemiology Research Group, Max Delbrueck Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany. 4. Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, Georgia. 5. Centre de Recherche en Epidémiologie et Santé des Populations, Université Paris-Sud, UVSQ, INSERM, Université Paris-Saclay, Villejuif, France; Institut Gustave Roussy, Villejuif, France. 6. German Cancer Research Center (DKFZ), Foundation under Public Law, Heidelberg, Germany. 7. Diet, Genes and Environment, Danish Cancer Society Research Center, Copenhagen, Denmark. 8. Diet, Genes and Environment, Danish Cancer Society Research Center, Copenhagen, Denmark; Department of Public Health, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. 9. Department of Public Health, Aarhus University, Aarhus, Denmark. 10. Department of Public Health, Aarhus University, Aarhus, Denmark; Department of Cardiology, Aalborg University Hospital, Aalborg, Denmark. 11. Functional Biology Department, School of Medicine, University of Oviedo, Asturias, Spain. 12. Unit of Nutrition and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology-IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain. 13. Escuela Andaluza de Salud Pública, Instituto de Investigación Biosanitaria ibs, Universidad de Granada, Granada, Spain; CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain. 14. Public Health Division of Gipuzkoa, BioDonostia Research Institute, San Sebastian, Spain. 15. CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain; Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca, Murcia, Spain. 16. CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain; Navarra Public Health Institute, Pamplona, Spain; IdiSNA, Navarra Institute for Health Research, Pamplona, Spain. 17. Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom. 18. Hellenic Health Foundation, Athens, Greece; School of Medicine, National and Kapodistrian University of Athens, Athens, Greece. 19. Nutrition and Metabolism Section, International Agency for Research on Cancer (IARC), Lyon, France; Department of Cardiology, Aalborg University Hospital, Aalborg, Denmark; 2nd Pulmonary Medicine Department, School of Medicine, National and Kapodistrian University of Athens, "ATTIKON" University Hospital, Haidari, Greece. 20. Hellenic Health Foundation, Athens, Greece. 21. Cancer Risk Factors and Life-Style Epidemiology Unit, Institute for Cancer Research, Prevention and Clinical Network - ISPRO, Florence, Italy. 22. Epidemiology and Prevention Unit Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy. 23. Cancer Registry and Histopathology Department, "M.P.Arezzo" Hospital, Ragusa, Italy. 24. Molecular Epidemiology and Exposomics Unit, Italian Institute for Genomic Medicine (IIGM), Torino, Italy. 25. Dipartimento di Medicina Clinica e Chirurgia Federico II University, Naples, Italy. 26. Department for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands; Department of Gastroenterology and Hepatology, University Medical Centre, Utrecht, The Netherlands; Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, St Mary's Campus, London, United Kingdom; Department of Social and Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia. 27. Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands. 28. Department of Clinical Sciences, Malmö, Diabetes and Cardiovascular Disease - Genetic Epidemiology, Lund University, Malmö, Sweden. 29. Department of Internal Medicine, Skåne University Hospital, Lund University, Malmö, Sweden. 30. Department of Public Health and Clinical Medicine, Section of Sustainable Health, Umeå University, Umeå, Sweden. 31. Department of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden. 32. Department of Community Medicine, University of Tromsø, Arctic University of Norway, Tromsø, Norway. 33. Office of the Director, International Agency For Research on Cancer (IARC), Lyon, France. 34. Department of Epidemiology and Biostatistics, School of Public Health, Imperial College, London, United Kingdom.
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.
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.
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