Effect of Individual Omega-3 Fatty Acids on the Risk of Prostate Cancer: A Systematic Review and Dose-Response Meta-Analysis of Prospective Cohort Studies

Epidemiological studies have suggested inconsistent associations between omega-3 polyunsaturated fatty acids (n-3 PUFAs) and prostate cancer (PCa) risk. We performed a dose-response meta-analysis of prospective observational studies investigating both dietary intake and circulating n-3 PUFAs and PCa risk. PubMed and EMBASE prior to February 2014 were searched, and 16 publications were eligible. Blood concentration of docosahexaenoic acid, but not alpha-linolenic acid or eicosapentaenoic acid, showed marginal positive association with PCa risk (relative risk for 1% increase in blood docosahexaenoic acid concentration: 1.02; 95% confidence interval, 1.00-1.05; I-2 = 26%; P = 0.05 for linear trend), while dietary docosahexaenoic acid intake showed a non-linear positive association with PCa risk (P < 0.01). Dietary alpha-linolenic acid was inversely associated with PCa risk (relative risk for 0.5 g/day increase in alpha-linolenic acid intake: 0.99; 95% confidence interval, 0.98-1.00; I-2 = 0%; P = 0.04 for linear trend), which was dominated by a single study. Subgroup analyses indicated that blood eicosapentaenoic acid concentration and blood docosahexaenoic acid concentration were positively associated with aggressive PCa risk and nonaggressive PCa risk, respectively. Among studies with nested case-control study designs, a 0.2% increase in blood docosapentaenoic acid concentration was associated with a 3% reduced risk of PCa (relative risk 0.97; 95% confidence interval, 0.94-1.00; I-2 = 44%; P = 0.05 for linear trend). In conclusion, different individual n-3 PUFA exposures may exhibit different or even opposite associations with PCa risk, and more prospective studies, especially those examining dietary n-3 PUFAs and PCa risk stratified by severity of cancer, are needed to confirm the results.