N-3 fatty acids may decrease risk of colorectal cancer by inhibiting the cyclooxygenase-2 enzyme and production of proinflammatory eicosanoids derived from arachidonic acid (20:4n-6). Aspirin also inhibits the cyclooxygenase-2 enzyme and may share with n-3 fatty acids a potential mechanism to decrease the risk of colorectal cancer. Methods: We conducted a nested case-control analysis using blood samples collected from the Physicians’ Health Study participants in 1982 to 1984. N-3 and n-6 fatty acid levels were measured using gas-liquid chromatography for 178 men who developed colorectal cancer through December 31, 1995 and 282 age-and smoking-matched controls. We used conditional logistic regression to examine associations. All statistical tests were two-sided. Results: Total long-chain n-3 fatty acids were not significantly inversely associated with colorectal cancer risk [relative risk (RR) for highest versus lowest quartile, 0.60; 95% confidence interval (95% CI), 0.32 to 1.11; Ptrend = 0.10], after adjustment for possible confounders. We observed potential interaction between randomized aspirin assignment and long-chain n-3 fatty acid levels (Pinteraction = 0.04). Among men not on aspirin, RRs (95% CI) for increasing quartiles of long-chain n-3 fatty acids were 1.00 (reference), 0.60 (0.28-1.28), 0.51 (0.22- 1.17), and 0.34 (0.15-0.82), Ptrend = 0.006. For participants taking aspirin, there was no additional benefit of increasing n-3 fatty acid levels. The RR (95% CI) for the highest versus lowest quartile of n-6 fatty acids was 0.64 (0.35-1.17). Conclusions: Blood levels of long-chain n-3 fatty acids were associated with decreased risk of colorectal cancer among men not using aspirin. N-6 fatty acids were not significantly inversely associated with colorectal cancer risk.
