Study Title:

Fish Oil and Aggressive Prostate Cancer

Study Abstract

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.

From press release:

Omega-3 fatty acids appear protective against advanced prostate cancer, and this effect may be modified by a genetic variant in the COX-2 gene, according to a report in Clinical Cancer Research, a journal of the American Association for Cancer Research.

"Previous research has shown protection against prostate cancer, but this is one of the first studies to show protection against advanced prostate cancer and interaction with COX-2," said John S. Witte, Ph.D., professor of epidemiology and biostatistics at the University of California San Francisco.

For the current study, researchers performed a case-control analysis of 466 men diagnosed with aggressive prostate cancer and 478 healthy men. Diet was assessed by a food frequency questionnaire and researchers genotyped nine COX-2 single nucleotide polymorphisms.

Researchers divided omega-3 fatty acid intake into four groups based on quartiles of intake. Men who consumed the highest amount of long chain omega-3 fatty acids had a 63 percent reduced risk of aggressive prostate cancer compared to men with the lowest amount of long chain omega-3 fatty acids.

The researchers then assessed the effect of omega-3 fatty acid among men with the variant rs4647310 in COX-2, a known inflammatory gene. Men with low long chain omega-3 fatty acid intake and this variant had a more than five-fold increased risk of advanced prostate cancer. But men with high intake of omega-3 fatty acids had a substantially reduced risk, even if they carried the COX-2 variant.

"The COX-2 increased risk of disease was essentially reversed by increasing omega-3 fatty acid intake by a half a gram per day," said Witte. "If you want to think of the overall inverse association in terms of fish, where omega-3 fatty acids are commonly derived, the strongest effect was seen from eating dark fish such as salmon one or more times per week."

Study Information

Vincent Fradet, Iona Cheng, Graham Casey, and John S. Witte.
Dietary Omega-3 Fatty Acids, Cyclooxygenase-2 Genetic Variation, and Aggressive Prostate Cancer Risk.
Clinical Cancer Research
2009 March
Departments of Urology and Epidemiology and Biostatistics and Institute for Human Genetics, University of California at San Francisco, San Francisco, California.

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