The role of genetic polymorphisms of N-acetyltransferase 2 (NAT2) enzyme in the risk of bladder cancer in the Lebanese population

Abstract

Introduction In Lebanon, bladder cancer has an unusually high prevalence. The correlation between N-acetyltransferase 2 (NAT2) polymorphisms and carcinogenesis is established in the literature for different types of cancers. Individuals who smoke and carry the slow acetylator phenotype may be at a higher risk of developing bladder cancer as NAT2 is unable to deactivate the carcinogenic aromatic amines found in cigarette smoke.Methods Data and DNA from 86 controls and 50 bladder cancer cases were analyzed. Seven NAT2 SNPs were genotyped using Restriction fragment length polymorphism technique (RFLP): C282T, G191A, C481T, G590A, G857A, A803G, and T341C. Haplotypes were constructed, and 2 phenotype groups were defined as follows: carriers of one or more NAT2*4 alleles were considered fast acetylators, and the rest were considered slow acetylators.Results A significantly higher percentage of patients with bladder cancer were males (79.6percent vs. 53.1percent) and smokers (67.3percent vs. 50.6percent). There was no difference in mean age between cases and controls (70.14+-- 11.87 vs. 71.95 +-- 17.98 respectively). The allele frequencies of the genotyped SNPs were comparable to Caucasian populations, and they were all in HWE. Sixty five percent were slow acetylators among controls, and 62percent were slow acetylators among cases, and this was not statistically different. No significant association was found between NAT2 phenotype and bladder cancer risk, even after adjusting for sex and smoking.Conclusion This is the first study on the association of NAT2 polymorphisms with bladder cancer risk in a Lebanese sample. Further recruitment is ongoing to increase the power of the study.