TY - JOUR TI - Consumption of Fish and Long-chain n-3 Polyunsaturated Fatty Acids Is Associated With Reduced Risk of Colorectal Cancer in a Large European Cohort AU - Aglago, E.K. AU - Huybrechts, I. AU - Murphy, N. AU - Casagrande, C. AU - Nicolas, G. AU - Pischon, T. AU - Fedirko, V. AU - Severi, G. AU - Boutron-Ruault, M.-C. AU - Fournier, A. AU - Katzke, V. AU - Kühn, T. AU - Olsen, A. AU - Tjønneland, A. AU - Dahm, C.C. AU - Overvad, K. AU - Lasheras, C. AU - Agudo, A. AU - Sánchez, M.-J. AU - Amiano, P. AU - Huerta, J.M. AU - Ardanaz, E. AU - Perez-Cornago, A. AU - Trichopoulou, A. AU - Karakatsani, A. AU - Martimianaki, G. AU - Palli, D. AU - Pala, V. AU - Tumino, R. AU - Naccarati, A. AU - Panico, S. AU - Bueno-de-Mesquita, B. AU - May, A. AU - Derksen, J.W.G. AU - Hellstrand, S. AU - Ohlsson, B. AU - Wennberg, M. AU - Van Guelpen, B. AU - Skeie, G. AU - Brustad, M. AU - Weiderpass, E. AU - Cross, A.J. AU - Ward, H. AU - Riboli, E. AU - Norat, T. AU - Chajes, V. AU - Gunter, M.J. JO - Clinical Gastroenterology and Hepatology PY - 2020 VL - 18 TODO - 3 SP - 654-666.e6 PB - W.B. Saunders SN - 1542-3565, 1542-7714 TODO - 10.1016/j.cgh.2019.06.031 TODO - omega 3 fatty acid; omega 6 fatty acid, adult; Article; ascending colon; cancer incidence; cancer localization; case control study; cohort analysis; colorectal cancer; controlled study; descending colon; dietary reference intake; disease association; European; fat intake; female; fish consumption; follow up; food frequency questionnaire; gas chromatography; hazard ratio; human; logistic regression analysis; major clinical study; male; middle aged; multicenter study; odds ratio; phospholipid blood level; proportional hazards model; prospective study; risk reduction; trend study; animal; colon tumor; diet; fish; sea food, Animals; Colonic Neoplasms; Diet; Fatty Acids, Omega-3; Fishes; Humans; Prospective Studies; Seafood TODO - 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. © 2020 AGA Institute ER -