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

Our plain-English summary of Polymorphisms in oxidative stress-related genes are not associated with prostate cancer risk in heavy smokers, by J.Y. Choi, M.L. Neuhouser, M. Barnett, et al (Cancer Epidemiology, Biomarkers & Prevention, 2007).

The study

• Authors: J.Y. Choi, M.L. Neuhouser, M. Barnett, M. Hudson, A.R. Kristal, M. Thornquist, I.B. King, G.E. Goodman, C.B. Ambrosone
• Journal: Cancer Epidemiology, Biomarkers & Prevention
• Published: 2007;16(6):1115-20
• Type of article: Randomized trial
• Cited by: 78 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

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.

In plain English

This nested case-control study used CARET, a lung cancer prevention trial among 18,314 heavy smokers and asbestos-exposed workers. It asked whether variants in three genes for enzymes defending against reactive oxygen species (MnSOD, CAT and GPX1) were linked to prostate cancer. Genetic results were available for 533 men with prostate cancer and 1,470 matched controls. Most analyses were limited to Caucasian men. Results were not reported separately by asbestos exposure. Overall, the variants showed no associations with prostate cancer risk. Among men diagnosed before age 65, the CAT TT genotype, compared with CC, had an odds ratio of 2.0 (95% CI 0.97-3.95). The authors cautioned this could be spurious, given multiple testing and small numbers. In a post hoc analysis, with the cutoff set from the observed data, men carrying five or six risk alleles across the three genes, versus fewer, had an odds ratio of 2.0 (95% CI 0.90-4.42); the authors noted this interval included 1. The authors concluded these variants may not play an important role in prostate cancer, particularly among heavy smokers and asbestos-exposed men.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Nested case-control study within a randomized prevention trial (CARET)
• Who was studied: Men in CARET, a multicenter trial of 18,314 heavy smokers and asbestos-exposed workers. Enrollment began in 1985, and active follow-up continued until 2005. Of 724 men with prostate cancer confirmed through 2003, 533 had genotyping data. They were compared with 1,470 controls matched on age, race/ethnicity and follow-up time. Most analyses were restricted to Caucasians.
• Exposure: Inherited variants in three oxidative stress-related genes: MnSOD Ala16Val, CAT 262 C>T and GPX1 Pro200Leu. All CARET participants were heavy smokers or had occupational asbestos exposure. The article does not report analyses by asbestos exposure. It examined vitamin supplement use, alcohol, BMI, smoking status and pack-years as possible modifiers.
• Main results:
  • Overall, across all cases and controls, there were no associations between the MnSOD, CAT or GPX1 variants and prostate cancer risk.
  • Among men diagnosed before age 65 (Caucasians only), the CAT TT genotype compared with CC had an odds ratio of 2.0 (95% CI 0.97-3.95; P for trend 0.079).
  • The genotypes were not associated with either nonaggressive or aggressive prostate cancer. The article does not show these data.
  • Among Caucasian men who never used vitamin supplements and had the MnSOD TT genotype, the odds ratio was 2.1 (95% CI 1.23-3.47), compared with supplement users with MnSOD TT genotypes. Smoking status and BMI did not seem to modify any of the gene-risk associations.
  • In an exploratory analysis, each man's 'risk' alleles (MnSOD C, CAT T and GPX1 T) were counted across the three genes, giving a count from 0 to 6. The cutoff of fewer than five risk alleles as the reference group was chosen post hoc, based on the distributions in cases and controls.
  • Caucasian men with five or six risk alleles, compared with men with fewer than five, had an odds ratio of 2.0 (95% CI 0.90-4.42). The authors called this marginally significant and noted that the confidence interval included unity.
• The authors' conclusion: The authors concluded that variants in MnSOD, CAT and GPX1 may not play an important role in the development of prostate cancer, particularly among heavy smokers and men with occupational asbestos exposure.
• Limitations the authors state:
  • All participants were heavy smokers or asbestos-exposed workers, so the results may not apply to other men.
  • Controls were free of prostate and lung cancer but not necessarily free of other cancers.
  • The CAT finding in men under 65 could be spurious because of multiple testing and small numbers in stratified analyses, and it needs replication.
  • There were too few African American men for separate analysis, so further analyses were limited to Caucasians.

Topics

Medical terms in this study, explained in our Lexicon: Oxidative Stress, Inflammation, Etiology, Reactive Oxygen Species (ROS), Lung Cancer, Asbestos Exposure, Odds Ratio, confidence interval.

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