Fish, Shellfish Associated with Advanced Prostate Protection

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Fish, Shellfish Associated with Advanced Prostate Protection

Fradet V, Cheng I, Casey G, Witte JS. Dietary omega-3 fatty acids, Cyclooxygenase-2 genetic variation, and aggressive prostate cancer risk. Clin Cancer Res 2009; DOI: 10.1158/1078-0432.CCR-08-2503.


Published online first on March 24, 2009
[Clinical Cancer Research, 10.1158/1078-0432.CCR-08-2503]

Susceptibility and Prevention
Dietary Omega-3 Fatty Acids, Cyclooxygenase-2 Genetic Variation, and Aggressive Prostate Cancer Risk
Vincent Fradet 1, 3, Iona Cheng 2, 3, Graham Casey 4, and John S. Witte 1, 2, 3*
Authors' Affiliations: Departments of 1Urology and 2Epidemiology and Biostatistics and 3Institute for Human Genetics, University of California at San Francisco, San Francisco, California and 4Department of Preventive Medicine, University of Southern California, Los Angeles, California

* To whom correspondence should be addressed. E-mail:


Purpose: Dietary intake of long-chain -3 (LC n-3) polyunsaturated fatty acids may reduce inflammation and in turn decrease risk of prostate cancer development and progression. This potential effect may be modified by genetic variation in cyclooxygenase-2 (COX-2), a key enzyme in fatty acid metabolism and inflammation.
Experimental Design: We used a case-control study of 466 men diagnosed with aggressive prostate cancer and 478 age- and ethnicity-matched controls. Diet was assessed with a semiquantitative food frequency questionnaire, and nine COX-2 tag single nucleotide polymorphisms (SNP) were genotyped. We used logistic regression models to estimate odds ratios (OR) for association and interaction.
Results: Increasing intake of LC n-3 was strongly associated with a decreased risk of aggressive prostate cancer (Ptrend 0.0001). The OR (95% confidence interval) for prostate cancer comparing the highest with the lowest quartile of n-3 intake was of 0.37 (0.25-0.54). The LC n-3 association was modified by SNP rs4648310 (+8897 A/G), flanking the 3' region of COX-2 (Pinteraction = 0.02). In particular, the inverse association was even stronger among men with this variant SNP. This reflected the observation that men with low LC n-3 intake and the variant rs4648310 SNP had an increased risk of disease (OR, 5.49; 95% confidence interval, 1.80-16.7), which was reversed by increasing intake of LC n-3.
Conclusions: Dietary LC n-3 polyunsaturated fatty acids appear protective for aggressive prostate cancer, and this effect is modified by the COX-2 SNP rs4648310. Our findings support the hypothesis that LC n-3 may impact prostate inflammation and carcinogenesis through the COX-2 enzymatic pathway.
Key Words: prostatic neoplasms, diet, polyunsaturated fatty acids, -3 fatty acids, cyclooxygenase-2, gene, genetic variation, single nucleotide polymorphism

Copyright © 2009 by the American Association for Cancer Research.