CYP2E1 and NQO1 genotypes, smoking and bladder cancer

Cytochrome P450 2E1 (CYP2E1) and NAD(P)H:quinone oxidoreductase (NQO1) catalyze the activation of some environmental procarcinogens present in tobacco smoke (i.e. nitrosoamines and heterocyclic amines). We conducted a hospital based case-control study to evaluate the potential association between genetic polymorphisms of CYP2E1 (C1019T in the 5' flanking region) and NQO1 (C609T in exon 6) and bladder cancer risk in Asian population.

The study population was comprised of 218 histologically confirmed prevalent bladder cancer cases and 199 controls without cancer or systemic illness. PCR-restriction fragment length polymorphism based methods were used for the genotyping analyses and unconditional logistic regression model for the statistical evaluations.

The risk of bladder cancer increased with the amount of smoking (P for trend < 0.01). The frequency of CYP2E1 c1/c1 genotype was significantly higher in bladder cancer patients (57.9%) than in the controls (47.9%) (OR = 1.8, 95% CI = 1.1-2.9). Similarly, the NQO1 C/C genotypes were significantly more prevalent in the patients (45.8%) than in the controls (37.6%) (OR = 1.6, 95% CI = 1.0-2.7). The risk for bladder cancer increased with the number of the putative risk genotypes (P for trend = 0.03); the most remarkable risk was observed for heavy smokers with both CYP2E1 c1/c1 and NQO1 C/C genotypes (OR = 13.8, 95% CI = 3.9-48.6) when compared to non/light smokers with other genotypes.

Our findings suggest that CYP2E1 and NQO1 genotypes may play an important role in development of smoking related bladder cancer among Korean men.