Dietary Omega-3 Fatty Acids, Cyclooxygenase-2 Genetic Variation, and Aggressive Prostate Cancer Risk

Abstract

Purpose: Dietary intake of long-chain N-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 (P trend V 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 (P interaction = 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.

SOCS3 Transactivation by PPARγ Prevents IL-17–Driven Cancer Growth

“…Dietary supplementation of DHA has been shown to alleviate the severity of intestinal inflammation (38,39) in experimental models of colitis and in inflammatory bowel disease in humans (40,41). These findings possibly explain why dietary (n-3) PUFAs intake was associated with decreased risk of cancer (42,43). However, recent data indicate that DHA also improves outcome of chemotherapy in patients with metastatic breast cancer, suggesting that it not only affects cancer incidence, but can be therapeutically used to prevent tumor growth (44).…”

El efecto de omega 3 en la salud humana y consideraciones en la ingesta

“…(37). Además, con la variante del gen COX-2, principal regulador de la vía infl amatoria, personas que contenían esta variante (rs4648310) relacionada con un alto consumo de omega 3 presentaron un menor riesgo de desarrollar cáncer de próstata comparado con las personas con bajos consumos (38). También, la Apolipoproteína E (Apo E) se ha asocia al consumo de omega 3.…”

Survival Disparities in Bladder, Kidney, and Prostate Cancer in Asian-Indian & Pakistani Immigrants to the United States as Compared to Other US Ethnic Groups: A Surveillance, Epidemiology and End Result (SEER) 2011 Public Use Database Study

“…Perhaps differences in sexual practices, carcinogen exposure, or hormonal environment may impact the clinical behavior of prostate cancers in US-AIP men. Recent studies have investigated the anti-inflammatory or biologic effects of omega-3 fatty acids (Fradet et al, 2009;Sugimoto et al, 2012), TMPRSS2-ETS gene fusions (Narod et al, 2008), and XML RNA tumor virus latency (Dong et al, 2007;Klein et al, 2008), in US men with prostate cancer. It might be useful to know if any of these are different in US-AIP men with prostate cancer.…”