Joint effect of N-acetyltransferase 2 gene and smoking status on bladder carcinogenesis in Algerian population

Background
Toxic compounds are detoxified by several xenobiotic metabolizing enzymes such as N-acetyltransferase 2 (NAT2). The role for NAT2 genetic polymorphisms in different malignancies risk has been the subject of numerous studies. In the current study we investigated the association of genetic NAT2 variants or their corresponding acetylator phenotypes with bladder cancer risk. The relationship between NAT2 genotype/phenotype and smoking status was also evaluated as potential risk factor of urinary bladder cancer.

Material and methods
As few data on the association between genetic polymorphisms of NAT2 and bladder cancer are available in the Algerian population, we performed an extensive identification of NAT2 variants in 175 bladder cancer patients and 189 healthy controls by direct PCR sequencing of the coding region.

Results
Thirteen previously described SNPs were identified in this study; only T341C and G590A were associated with increased risk of bladder cancer (P < 0.05). NAT2 slow acetylator phenotype is at higher risk (OR = 2.45, 95% CI = 1.41–4.35) with the greatest risk noted for the allele NAT2*5. When combined to smoking status, T341C and G590A SNPs were of significant correlation with bladder cancer risk (P < 0.05) among non smokers. A correlation that increased among smokers. However, a relationship emerged only when smoking habit was considered between C345T, C481T and A803G SNPs and bladder cancer risk (P < 0.05). Our study showed a strong interaction between NAT2 slow acetylator phenotype and smoking (P = 7.20e^-6).

Conclusions
These findings provided evidence of an additive effect between smoking status and NAT2 slow acetylation in influencing bladder cancer risk.