Distribution and Role of N-acetyltransferase 2 Genetic Polymorphisms in Bladder Cancer Risk in a Lebanese Population

Background: In Lebanon, bladder cancer (BC) has an unusually high prevalence. Individuals who are exposed to aromatic amines from smoking or certain occupations and carrying the slow N-acetyl transferase 2 (NAT2) acetylator’ phenotype may be at a higher risk. Methods: Data and DNA from 115 Lebanese BC cases and 306 controls were examined. Ten NAT2 single nucleotide polymorphisms were genotyped, seven of which were then included in haplotype and phenotype analysis. Results: BC patients were more likely to be males (87.8% vs. 54.9%) and current smokers (60.9% vs. 26.5%) when compared to controls. In both groups, most participants had the slow NAT2 acetylator phenotype (66.1% of BC cases vs 62.7% of controls; P=0.302) with the NAT2*5B and *6A haplotypes being the most common. The odds ratio (95%CI) of having BC among slow NAT2 acetylators was 1.157 (0.738-1.815) and remained non-significant after adjustment [1.097 (0.666-1.806)]. Sensitivity analysis with a subgroup of 113 cases and 84 controls for which occupational history was available revealed a statistically significant association between slow NAT2 acetylators and BC in females only. The sample size was however very small and the CI quite wide. Conclusions: This is the first study to evaluate the distribution of NAT2 haplotypes and their potential role in BC in a Lebanese population. The absence of any significant association may be due to the relatively small sample size, the unavailability of matching by gender, and the lack of evaluation of genetic interactions with extent of active and passive smoking, exposure to environmental pollutants, diet, and other genes. The potential association limited to females needs further evaluation.