Joint effect among p53, CYP1A1, GSTM1 polymorphism combinations and smoking on prostate cancer risk: an exploratory genotype-environment interaction study

Asian J Androl. 2006 May;8(3):349-55. doi: 10.1111/j.1745-7262.2006.00135.x.

Abstract

Aim: To assess the role of several genetic factors in combination with an environmental factor as modulators of prostate cancer risk. We focus on allele variants of low-penetrance genes associated with cell control, the detoxification processes and smoking.

Methods: In a case-control study we compared people carrying p53cd72 Pro allele, CYP1A1 M1 allele and GSTM1 null genotypes with their prostate cancer risk.

Results: The joint risk for smokers carrying Pro* and M1*, Pro* and GSTM1null or GSTM1 null and CYP1A1 M1* variants was significantly higher (odds ratio [OR]: 13.13, 95% confidence interval [CI]: 2.41-71.36; OR: 3.97, 95% CI: 1.13-13.95 and OR: 6.87, 95% CI: 1.68-27.97, respectively) compared with that for the reference group, and for non-smokers was not significant. OR for combinations among p53cd72, GSTM1 and CYP1A1 M1 in smokers were positively and significantly associated with prostate cancer risk compared with non-smokers and compared with the putative lowest risk group (OR: 8.87, 95% CI: 1.25-62.71).

Conclusion: Our results suggest that a combination of p53cd72, CYP1A1, GSTM1 alleles and smoking plays a significant role in modified prostate cancer risk on the study population, which means that smokers carrying susceptible genotypes might have a significantly higher risk than those carrying non-susceptible genotypes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Confidence Intervals
  • Cytochrome P-450 CYP1A1 / genetics*
  • Gene Amplification
  • Genes, p53*
  • Genetic Variation
  • Genotype
  • Glutathione Transferase / genetics*
  • Humans
  • Male
  • Middle Aged
  • Polymerase Chain Reaction
  • Polymorphism, Genetic*
  • Prostatic Neoplasms / epidemiology
  • Prostatic Neoplasms / genetics*
  • Risk Factors
  • Smoking

Substances

  • Cytochrome P-450 CYP1A1
  • Glutathione Transferase
  • glutathione S-transferase M1