Background: Previous results of the association between n-3 polyunsaturated fatty acids (PUFA) and colorectal cancer were inconsistent. We conducted a systematic review and meta-analysis of prospective studies.

Methods: The PubMed and Embase databases were searched through July 10, 2019, followed by a manual search. A random-effects model was used.

Results: Twenty prospective studies, including 18,102 cases and 1,360,046 participants, were included. The pooled RR of colorectal cancer for the highest versus lowest category of n-3 PUFA intake was 0.97 [95% confidence interval (CI), 0.90-1.04]. Regarding the type of n-3 PUFA, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) intakes were inversely associated with 11% (RR = 0.89; 95% CI, 0.80-0.99) and 12% (RR = 0.88; 95% CI, 0.81-0.96) lower colorectal cancer risks, respectively, in the comparison of the highest versus lowest category. Increments of 0.1 g/day of EPA (RR = 0.95; 95% CI, 0.92-0.98) and DHA (RR = 0.97; 95% CI, 0.95-0.99) intakes were associated with a lower colorectal cancer risk. Regarding the blood levels of n-3 PUFAs, the pooled RR of colorectal cancer for the highest versus lowest category of blood levels of n-3 PUFAs was 0.79 (95% CI, 0.64-0.98). The risk of colorectal cancer decreased by 4% for every 1% increase in blood n-3 PUFA levels (RR = 0.96; 95% CI, 0.92-1.00).

Conclusions: High blood n-3 PUFA levels are inversely associated with colorectal cancer risk, and high n-3 PUFA intake is suggestively associated with lower colorectal cancer risk.

Impact: Our findings suggest that high blood n-3 PUFA levels may be associated with reduced colorectal cancer risk, but further studies are needed.