NAT2 gene polymorphism as a possible marker for susceptibility to bladder cancer in Japanese

Background: N-acetyltransferase (NAT) is known to metabolize the carcinogen arylamine. The polymorphism of the NAT2 gene is an important determinant of individual susceptibility to bladder cancer. There are significant interethnic differences in NAT2 allele frequencies, The relationship between NAT2 genotypes and bladder cancer in a Japanese population was investigated. Methods: A case control study on 85 bladder cancer patients and 146 control subjects was conducted. NAT2 alleles were differentiated by polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP) methods using originally created PCR primers and genomic DNA extracted from peripheral white blood cells. The NAT2 genotypes were determined by the combination of three known NAT2 mutant type alleles (M1, M2, M3) and the wild type allele. Results: NAT2 slow genotypes were associated with bladder cancer risk (odds ratio adjusted for age and gender, 4.23; 95% confidence interval [CI], 1.76-10.81). Among those with NAT2 slow genotypes/smoker, there was a significantly increased risk of 7.80 (95% CI, 1.66-57.87) when the NAT2 rapid genotypes/non-smoker were considered the reference group. This suggested a possible interaction between NAT2 slow genotypes/smoking status and bladder cancer risk. It was also shown that bladder cancer patients with NAT2 slow genotypes were more likely to have a high grade tumor (G3) or an advanced stage tumor (<pT2-pT4). However, no association between NAT2 genotypes and the survival rate of invasive bladder cancer patients was recognized. Conclusion: It was demonstrated that the NAT2 slow acetylation genotype is an important genetic determinant for bladder cancer in a Japanese population.