GST, NAT, SULT1A1, CYP1B1 genetic polymorphisms, interactions with environmental exposures and bladder cancer risk in a high-risk population

摘要: Tobacco smoking and occupation are major risk factors of bladder cancer via exposure to polycyclic aromatic hydrocarbons (PAHs) amines. Glutathione S-transferase (GST) M1, T1 P1 involved in the detoxification PAH reactive metabolites. Two N-acetyltransferase isozymes, NAT2 NAT1, have roles catalyzing N-acetylation O-acetylation Cytochrome p450 1B1 (CYP1B1) sulfotransferase 1A1 (SULT1A1) also metabolism PAHs It is hypothesized that genetic polymorphisms these metabolic enzymes an effect on individual susceptibility particular by interacting with relevant environmental exposures. A hospital-based case-control study among men Brescia, Northern Italy recruited 201 incidence cases 214 controls from 1997-2000. Occupational exposures were blindly coded occupational physicians. Genotyping carried out PCR-RFLP method. Unconditional multivariate logistic regression was applied model association between risk. Effect modifications age onset, amines evaluated. We conducted analysis interaction factors. GSTM1 GSTT1 null genotype associated increased odds ratio (OR) 1.69 (95% confidence interval [CI] = 1.11-2.56) 1.74 CI 1.02-2.95), respectively. The seen particularly heavy smokers, there a combined (OR 2.77, 95% 1.08-7.10). observed trend (p-value < 0.01) increasing comparing subjects normal activity one 1.82, 1.16-2.85) or both genotypes 2.58, 1.27-5.23). slow acetylator marginally 1.50, 0.99-2.27), OR for joint 3.26 1.06-9.95). SULT1A1 Arg213His polymorphism showed marginal protective effect. These findings suggest may be modulated GSTM1, polymorphisms.