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A Prospective Study of Polyunsaturated Fatty Acid Levels in Blood and Prostate Cancer Risk

Departments of ¹ Nutrition and ² Epidemiology, Harvard School of Public Health and ³ The Channing Laboratory and ⁴ Divisions of Aging and Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts

Requests for reprints: Jorge E. Chavarro, Department of Nutrition, Harvard School of Public Health, 665 Huntington Avenue, Boston, MA 02115. Phone: 617-432-4584; Fax: 671-432-2435. E-mail: jchavarr{at}hsph.harvard.edu

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 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 -linolenic and dihomo--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 -linolenic and RR, 1.54; 95% CI, 1.03-2.30; P_trend = 0.02 for dihomo--linolenic acid). Levels of arachidonic and -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. (Cancer Epidemiol Biomarkers Prev 2007;16(7):1364–70)

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