Consumption of n-3 Fatty Acids and Fish Reduces Risk of Hepatocellular Carcinoma

BACKGROUND & AIMS: Fish is a rich source of n-3 polyunsaturated fatty acids (PUFAs), such as eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA). Although consumption of fish and n-3 PUFA has been reported to protect against the development of some types of cancer, little is known about its association with hepatocellular carcinoma (HCC). METHODS: We investigated the association between fish and n-3 PUFA consumption and HCC incidence (n = 398) in a population-based prospective cohort study of 90,296 Japanese subjects (aged, 45-74 y). Hazard ratios and 95% confidence intervals (CIs) for the highest vs the lowest quintile were estimated from multivariable adjusted Cox proportional hazards regression models. We also conducted subanalyses of subjects with known hepatitis B virus (HBV) or hepatitis C virus (HCV) status, and of subjects who were anti-HCV and/or hepatitis B surface antigen positive. All tests of statistical significance were 2-sided. RESULTS: Among all subjects, consumption of n-3 PUFA-rich fish and individual n-3 PUFAs was associated inversely with HCC, in a dose-dependent manner. Hazard ratios for the highest vs lowest quintiles were 0.64 (95% CI, 0.42-0.96) for n-3 PUFA-rich fish, 0.56 (95% CI, 0.36-0.85) for EPA, 0.64 (95% CI, 0.41-0.98) for DPA, and 0.56 (95% CI, 0.35-0.87) for DHA. These inverse associations were similar irrespective of HCV or HBV status. CONCLUSIONS: Consumption of n-3 PUFA-rich fish or n-3 PUFAs, particularly EPA, DPA, and DHA, appears to protect against the development of HCC, even among subjects with HBV and/or HCV infection.