title: Joint effect among p53, CYP1A1, GSTM1 polymorphism combinations and smoking on prostate cancer risk: an exploratory genotype-environment interaction study.
abstract: 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.
authors.affiliation: Laboratory of Chemical Carcinogenesis and Pharmacogenetics, Faculty of Medicine, Biomedical Science Institute (ICBM), University of Chile, Santiago, Chile.
authors.forename: Luis A
authors.initials: LA
authors.lastname: Quiñones
authors.forename: Carlos E
authors.initials: CE
authors.lastname: Irarrázabal
authors.forename: Claudio R
authors.initials: CR
authors.lastname: Rojas
authors.forename: Cristian E
authors.initials: CE
authors.lastname: Orellana
authors.forename: Cristian
authors.initials: C
authors.lastname: Acevedo
authors.forename: Christian
authors.initials: C
authors.lastname: Huidobro
authors.forename: Nelson E
authors.initials: NE
authors.lastname: Varela
authors.forename: Dante D
authors.initials: DD
authors.lastname: Cáceres
mesh_terms: 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
chemical_list: D019363:Cytochrome P-450 CYP1A1; D005982:Glutathione Transferase