Inducible nitric oxide synthase promoter polymorphism; cigarette smoking; and urothelial carcinoma risk

OBJECTIVES: Bladder carcinoma has a high inducible nitric oxide synthase (iNOS) content, and a highly polymorphic (CCTTT)n repeat in the iNOS promoter region has been identified. We explored whether this iNOS promoter polymorphism and cigarette smoking are associated with urothelial carcinoma (UC) risk.

METHODS: A total of 250 patients with pathologically confirmed UC and 250 unrelated noncancer controls were serially recruited at the Chia Yi Christian Hospital from August 2002 to May 2005. Multivariate logistic regression analysis was used to calculate the odds ratio and 95% confidence interval (CI).

RESULTS: A significantly increased UC risk was found in those who had smoked more than 30 years (odds ratio 2.4, 95% CI 1.5 to 4.2). The study subjects carrying the 12-repeat allele had a significantly increased UC risk (odds ratio 1.7, 95% CI 1.1 to 2.5). We also found the investigated polymorphism was related to clinical stage (P = 0.043). Of those who had ever smoked, those with the short/long (S/L) and long/long (L/L) genotypes (S, 9 to 11 repeats; L, 12 to 18 repeats) and the 12-repeat allele had a significantly increased UC risk of 3.5 (95% CI 1.7 to 7.3) and 4.5 (95% CI 2.2 to 8.9), respectively. Of the study subjects who had smoked longer than 30 years, those with S/L and L/L genotypes and the 12-repeat allele had significantly increased UC risks of 2.4 (95% CI 1.3 to 4.7) and 3.8 (95% CI 1.8 to 8.0), respectively.

CONCLUSIONS: These findings suggest that the polymorphic (CCTTT)n repeat in the iNOS promoter region might be involved in the development of UC, especially in those who have ever smoked.