A prospective study of fish, n-3 fatty acid intake, and colorectal cancer risk in men.

B165

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 by inhibiting the cyclooxygenase-2 (COX-2) enzyme and the production of arachidonic acid (n-6) derived eicosanoids. While animal studies provide support for this hypothesis, consistent results have not emerged from studies in humans. We previously reported an inverse association between blood levels of long-chain n-3 fatty acids and colorectal cancer risk as well as an interaction between n-3 fatty acids and aspirin from a case-control study nested within the Physicians' Health Study (PHS). Here we report on the association between fish and n-3 fatty acid intake and colorectal cancer risk using data from the full PHS cohort. Methods: The PHS began as a randomized, double blind, placebo-controlled, factorial trial to examine the effect of aspirin and β-carotene supplementation on cancer and cardiovascular disease. The 22 071 participants had no history of cardiovascular disease or cancer at the start of the study in 1982. Fish intake was assessed at the 12 month follow-up using an abbreviated food-frequency questionnaire which asked about average intake of 4 types of fish/shellfish. From this information, we calculated the average daily intake of fish and n-3 fatty acids from fish. Participants reported the diagnosis of colorectal cancer on annual follow-up questionnaires. Cox proportional hazards models were used to estimate the relative risk (RR) of colorectal cancer for categories of fish intake and quartiles of n-3 fatty acid intake from fish. Results: Participants were followed for an average of 19.4 years and there were 501 confirmed cases of colorectal cancer. The percentage of men consuming fish <1 time per week, 1 - <2 times per week, 2 - <5 times per week, and greater than 5 times per week were 9.6%, 31.1%, 48.4%, and 10.9%. The multivariate RRs (95% confidence interval (CI)) for increasing categories of fish intake were 1.00 (ref.), 0.87 (0.64-1.19), 0.80 (0.60-1.08), and 0.60 (0.40-0.91) (P_trend = 0.01). Our findings for n-3 fatty acids were similar to those for fish. Results from the multivariate model showed a statistically significant inverse trend (p = 0.01) with RRs (95% CI) for increasing quartiles of 1.00 (ref.), 0.92 (0.72-1.16), 0.80 (0.63-1.03), and 0.74 (0.57-0.95). Similar results were observed for both colon and rectal cancers; the RRs for the highest versus lowest category of fish intake were 0.59 (0.36 - 0.95) for colon cancers and 0.62 (0.28 - 1.35) for rectal cancers. We did not observe a statistically significant interaction between fish or n-3 fatty acid intake and aspirin. Conclusions: Our results suggest that fish and long-chain n-3 fatty acids from fish may decrease the risk of colorectal cancer.