Association between SNPs of MnSOD, CAT, and GPX1 and exposures that impact oxidative stress on the risk of prostate cancer.

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Oxidative stress appears to be a risk factor for prostate cancer. Thus, we evaluated potential associations between risk and gene variants that result in reduced neutralization of reactive oxygen species (ROS) (MnSOD Ala-9Val, CAT -262 C>T, and GPX1 -198 C>T) in the Carotene and Retinol Efficacy Trial (CARET) cohort, among which there were 737 incident prostate cancers after an average follow up of 11 years. Odds ratios (OR) and95% confidence intervals (95% CI) were estimated by logisticregression. In nested case-controls analyses based on 546 cases and 1,474 controls matched for race, age, and length of follow-time with DNA available, findings differed little by genotypes of MnSOD, CAT, or GPX1 in overall or stratified analyses. However, when calculating the number of risk alleles of MnSOD, CAT, and GPX1 (reduced protection against ROS), men with more than 4 risk alleles had significantly increased risk of prostate cancer compared to men with less than 5 risk alleles (adjusted OR=2.5, 95% CI=1.10-5.73). Results were strongest among men with greater exposure to sources of oxidative stress, with increased risk for men who had more than 4 alleles and were heavy smokers (> 60 packyears) (OR=4.1, 95% CI=1.06-15.53), higher consumers of alcoholic beverages (OR=5.0, 95% CI=1.72-14.27), or non-users of vitamin supplements (OR=3.2, 95% CI=1.07-9.88). These results indicate that SNPs in genes relevant to ROS may play an important role in the development of prostate cancer, particularly among men with greater exposure to ROS.