Polymorphisms in oxidative stress-related genes are not associated with prostate cancer risk in heavy smokers.

Abstract

Oxidative stress, associated with aging and inflammation, is likely to play a role in the etiology of prostate cancer. We evaluated potential associations between gene variants that result in reduced neutralization of reactive oxygen species (ROS; MnSOD Ala-16Val, CAT -262 C>T, and GPX1 Pro200Leu) and prostate cancer risk among 724 men with incident prostate cancer who participated in the Carotene and Retinol Efficacy Trial (CARET) cohort, a randomized trial for the prevention of lung cancer among men with a history of smoking and/or asbestos exposure. Odds ratios (OR) and 95% confidence intervals (95% CI) were estimated by logistic regression. Nested case-control analyses included study participants with available DNA (n = 533 cases and 1,470 controls), matched for race, age, and length of follow-time. Overall, there were no associations between genotypes of MnSOD, CAT, and GPX1 and prostate cancer risk, although among men diagnosed before age 65, CAT TT genotype was associated with increased risk (OR, 2.0; 95% CI, 0.97-3.95). Further analyses stratified by factors related to environmental oxidative stress exposures did not modify associations. When calculating the number of risk alleles of MnSOD, CAT, and GPX1 hypothetically related to reduced protection against ROS, there was a nonsignificant relationship between prostate cancer and carriage of five or more risk alleles, in comparison to men with less than five risk alleles (OR, 2.0; 95% CI, 0.90-4.42). In conclusion, it does not seem that variants in MnSOD, CAT, or GPX1 have an influence on prostate cancer risk in this cohort of men who were smokers or exposed to asbestos, although it is possible that cumulative defects in protection from oxidative stress may result in increased risk of the disease.

• Authors: Ji-Yeob Choi, Marian L Neuhouser, Matt Barnett, Matthew Hudson, Alan R Kristal, Mark Thornquist, Irena B King, Gary E Goodman, Christine B Ambrosone
• Journal: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology (Cancer Epidemiol Biomarkers Prev) Vol. 16 Issue 6 Pg. 1115-20 (Jun 2007) ISSN: 1055-9965 [Print] United States
• PMID: 17548672 (Publication Type: Clinical Trial, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, N.I.H., Extramural)

Chemical References

• Asbestos
• Catalase
• Glutathione Peroxidase
• Superoxide Dismutase

Topics

• Age of Onset
• Asbestos (adverse effects)
• Case-Control Studies
• Catalase (genetics)
• Double-Blind Method
• Genetic Predisposition to Disease
• Glutathione Peroxidase (genetics)
• Humans
• Male
• Occupational Exposure (adverse effects)
• Oxidative Stress (genetics)
• Polymorphism, Genetic
• Prostatic Neoplasms (genetics)
• Smoking (adverse effects)
• Superoxide Dismutase (genetics)