Genotypes of N-acetyltransferase-2 and risk of bladder cancer: A case-control study

Purpose: This study was conducted to examine whether certain slow N-acetyla tion genotypes could be risk factors for bladder cancer, and the possible a ssociation between specific genotypes and the severity of the disease at fi rst diagnosis. Materials and Methods: This case-control study included 89 patients with tr ansitional cell bladder cancer (diagnosed over a period of 21 months) and 1 47 controls. N-acetyltransferase-2 (NAT-8) genotypes were identified by all ele specific polymerase chain reaction (PCR) on peripheral blood DNA sample s. The x(2) test was used for statistical evaluation to compare the differe nces observed between patients and controls and the different genotypes wit h tumor grading and local staging at presentation. Relative, attributable a nd population attributable risks were estimated for the genotypes found to present a significantly increased frequency for bladder cancer. Results: A statistically significant difference in the frequency of genotyp es was found between the two groups. The patient group had the higher frequ ency of slow acetylation genotypes (p = 0.0016). Among slow acetylators, ho mozygotes 341C/341C and compound heterozygotes 341C/857A had the most, exce ssive risk for bladder cancer (p = 0.0041 and 0.0031, respectively). The 34 1C/341C genotype was found to be associated with more aggressive disease, i n terms of tumor grading at presentation (p < 0.05). Conclusions: According to our data, slow acetylators with 341C/341C and 341 C/857A genotypes carry a substantially higher odds ratio (3.73 and 12.46, r espectively) for,ladder carcinogenesis. Additionally, among the slow acetyl ators, 341C/341C homozygotes are likely to have a higher risk for more aggr essive disease.