Consumption of n-3 fatty acids and fish reduces risk of hepatocellular carcinoma

Gastroenterology. 2012 Jun;142(7):1468-75. doi: 10.1053/j.gastro.2012.02.018. Epub 2012 Feb 16.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Animals
  • Carcinoma, Hepatocellular / prevention & control*
  • Carcinoma, Hepatocellular / virology
  • Diet*
  • Fatty Acids, Omega-3 / administration & dosage*
  • Female
  • Fishes*
  • Hepatitis B / complications
  • Hepatitis C / complications
  • Humans
  • Japan
  • Liver Neoplasms / prevention & control*
  • Liver Neoplasms / virology
  • Male
  • Middle Aged
  • Proportional Hazards Models
  • Risk
  • Surveys and Questionnaires


  • Fatty Acids, Omega-3