Association of polymorphisms in iNOS and NQO1 with bladder cancer risk in cigarette smokers

Background: NAD(P)H:quinine oxidoreductase (NQO1) plays an important role in the metabolism of several carcinogens contained in cigarettes. Inducible nitric oxide synthase (iNOS) expression had been detected in urinary bladder tumors. The aim of this study was to investigate the interaction of iNOS and NQO1 on bladder cancer (BC) risk stratified by cigarette smoking status. Methods: A total of 159 BC patients and 150 cancer-free controls were recruited from December 2003 to November 2004. Genotyping of NQO1 rs1800566 polymorphism and iNOS (CCTTT)n pentanucleotide repeat polymorphism was determined using the polymerase chain reaction-restricted fragment length polymorphism and sequencing method. The odds ratio and 95% confidence interval (CI) were calculated as a measure of the joint effect of NQO1 rs1800566 and iNOS (CCTTT)n polymorphisms on BC risk among cigarette smokers. Results: Compared with study participants carrying the C/C genotype of NQO1 gene, those with C/T and T/T genotypes had a significantly increased BC risk of 1.8 (95% CI = 1.1-2.9). Among cigarette smokers, those who carried the 12-repeat allele of iNOS (CCTTT)n polymorphism had a significantly increased BC risk of 2.7 (95% CI = 1.0-6.7). Furthermore, a significant combined effect of the C/T and T/T genotypes of NQO1gene and the 12-repeat allele of iNOS (CCTTT)n repeat polymorphism on BC was found among cigarette smokers (odds ratio = 4.4, 95% CI = 1.3-14.9). Conclusion: Our findings suggest that a significant combined effect of NQO1 C/T and T/T genotypes and the 12-repeat allele of iNOS (CCTTT)n polymorphism on BC exists, especially in those with the habit of cigarette smoking.