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

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.