A prospective study of polyunsaturated fatty acid levels in blood and prostate cancer risk.

BACKGROUND: Animal models suggest that n-3 fatty acids inhibit prostate cancer proliferation, whereas n-6 fatty acids promote it, but epidemiologic studies do not uniformly support these findings. METHODS: A nested case-control study was conducted among 14,916 apparently healthy men who provided blood samples in 1982. Blood fatty acid levels were determined for 476 men diagnosed with prostate cancer during a 13-year follow-up and their matched controls. Conditional logistic regression was used to estimate the relative risks (RR) and 95% confidence intervals (95% CI) of total, non-aggressive (stage A/B and Gleason < 7) and aggressive (stage C/D, Gleason >or= 7, subsequent distant metastasis or death) prostate cancer associated with blood levels of specific fatty acids expressed as percentages of total fatty acids. RESULTS: Whole blood levels of all long-chain n-3 fatty acids examined and of linoleic acid were inversely related to overall prostate cancer risk (RR(Q5vs.Q1), 0.59; 95% CI, 0.38-0.93; P(trend) = 0.01 for total long-chain n-3 fatty acids and RR(Q5vs.Q1), 0.62; 95% CI, 0.41-0.95; P(trend) = 0.03 for linoleic). Blood levels of gamma-linolenic and dihomo-gamma-linolenic acids, fatty acids resulting from the metabolism of linoleic acid, were directly associated with prostate cancer (RR, 1.41; 95% CI, 0.94-2.12; P(trend) = 0.05 for gamma-linolenic and RR, 1.54; 95% CI, 1.03-2.30; P(trend) = 0.02 for dihomo-gamma-linolenic acid). Levels of arachidonic and alpha-linolenic acids were unrelated to prostate cancer. CONCLUSIONS: Higher blood levels of long-chain n-3 fatty acids, mainly found in marine foods, and of linoleic acid, mainly found in non-hydrogenated vegetable oils, are associated with a reduced risk of prostate cancer. The direct associations of linoleic acid metabolites with prostate cancer risk deserve further investigation.