Background: Whether the intake of eicosapentaenoic acid (EPA) or arachidonic acid (AA) affects the risk of cancer remains unclear, and the association between the serum EPA:AA ratio and cancer risk has not been fully evaluated in general populations. Methods: A total of 3098 community-dwelling subjects aged ≥40 years were followed up for 9.6 years (2002-2012). The levels of the serum EPA:AA ratio were categorized into quartiles (< 0.29, 0.29-0.41, 0.42-0.60, and > 0.60). The risk estimates were computed using a Cox proportional hazards model. The same analyses were conducted for the serum docosahexaenoic acid to arachidonic acid (DHA:AA) ratio and individual fatty acid concentrations. Results: During the follow-up period, 121 subjects died of cancer. Age- and sex-adjusted cancer mortality increased with lower serum EPA:AA ratio levels (P trend < 0.05). In the multivariable-adjusted analysis, the subjects in the first quartile of the serum EPA:AA ratio had a 1.93-fold (95% confidence interval, 1.15-3.22) greater risk of cancer death than those in the fourth quartile. Lower serum EPA concentrations were marginally associated with higher cancer mortality (P trend < 0.11), but the serum DHA or AA concentrations and the serum DHA:AA ratio were not (all P trend > 0.37). With regard to site-specific cancers, lower serum EPA:AA ratio was associated with a higher risk of death from liver cancer. However, no such associations were detected for deaths from other cancers. Conclusions: These findings suggest that decreased level of the serum EPA:AA ratio is a significant risk factor for cancer death in the general Japanese population.
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