A 22-year Prospective Study of Fish, n-3 Fatty Acid Intake, and Colorectal Cancer Risk in Men

Background: Fish is the main dietary source of long-chain n-3 fatty acids, which have been suggested to play a protective role in colorectal cancer development in laboratory and animal studies. Human studies have not shown consistent results. We examined the association between intakes of fish and n-3 fatty acids from fish and colorectal cancer risk in men enrolled in the Physicians' Health Study. Methods: The Physicians' Health Study began as a randomized trial to examine the effect of aspirin and β-carotene supplementation on cancer and cardiovascular disease. Fish intake was assessed at the 12-month follow-up with an abbreviated food-frequency questionnaire. Cox proportional hazards models were used to estimate multivariate relative risks for colorectal cancer for the categories of fish intake and quartiles of n-3 fatty acid intake. Results: During 22 years of follow-up, 500 men had a confirmed diagnosis of colorectal cancer. Fish intake was inversely associated with colorectal cancer risk [multivariate relative risk (95% confidence interval) for highest versus lowest category, 0.60 (0.40-0.91); Ptrend = 0.01]. The inverse association was observed for both colon and rectal cancers. Our findings for n-3 fatty acids were similar to those for fish; the multivariate relative risk (95% confidence interval) of total colorectal cancer for the highest versus lowest quartile of n-3 fatty acids was 0.74 (0.57-0.95; Ptrend = 0.01). Conclusions: Our results from this long-term prospective study suggest that intakes of fish and long-chain n-3 fatty acids from fish may decrease the risk for colorectal cancer. (Cancer Epidemiol Biomarkers Prev 2008;17(5):1136–43)