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


CONCLUSIONS
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.
Quiñones
Luis A
LA
Laboratory of Chemical Carcinogenesis and Pharmacogenetics, Faculty of Medicine, Biomedical Science Institute (ICBM), University of Chile, Santiago, Chile.
Irarrázabal
Carlos E
CE
Rojas
Claudio R
CR
Orellana
Cristian E
CE
Acevedo
Cristian
C
Huidobro
Christian
C
Varela
Nelson E
NE
Cáceres
Dante D
DD
D000368:Aged; D016001:Confidence Intervals; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics*; D005784:Gene Amplification; D016158:Genes, p53; D014644:Genetic Variation; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011471:Prostatic Neoplasms / Q000453:epidemiology / Q000235:genetics*; D012307:Risk Factors; D012907:Smoking
D019363:Cytochrome P-450 CYP1A1; D005982:Glutathione Transferase