NAT2 gene polymorphism is associated with susceptibility to bladder cancer in Slovak population dependently on smoking

L Klimčáková MD^a, MD Habalová^a, J Šalagovič MD^a, K Harčová MD^a, Prof Kalina^a, M Hrivňák MD^b, M Iláš MD^b

^aDepartment of Medical Biology, School of Medicine, P. J. Šafárik University, Slovakia, Slovakia, ^bDepartment of Urology, University Hospital, Košice, Slovakia

AIM: N-acetyltransferase 2 (NAT2), one of two NAT isozymes in humans, is involved in metabolic activation/inactivation of various therapeutic and environmental agents with carcinogenic potential. The observation of hereditary polymorphisms in the NAT2 gene resulting in identification of slow- and rapid-acetylator individuals has focused the interest on their role to modulate risk of certain malignancies. Aim of the study was to evaluate the impact of the NAT2 gene polymorphism on the susceptibility to bladder cancer in Slovak population. METHODS: We determined the NAT2 phenotype and genotype distribution in a group of 110 Slovak bladder cancer patients and 246 population healthy controls. Four point mutations of the NAT2 gene (C 481T, G 590A, A 803G and G 857A) were analyzed by using PCR-RFLP method to detect six most common alleles (NAT2*4, *5A, *5B, *5C, *6, and *7). RESULTS: The expected positive correlation between slow acetylator phenotype and the risk of the disease was confirmed (OR 1.92; 95% CI 1.16-3.19). In addition, after grouping by smoking status, the risk increased to an OR 2.16 (95% CI 1.04-4.52) for slow acetylators among smokers. When studied genotype distribution separately, the significantly increased risk was found out for individuals with slow acetylation NAT2*5B/*6 genotype (OR 1.76; 95% CI 1.04-3.16) and the highest risk we observed among males possessing NAT2*5B/*6 genotype (OR 2.48; 95% CI 1.16-5.43). CONCLUSIONS: Our preliminary findings that NAT2 acetylation polymorphism affects the susceptibility to bladder cancer dependently on smoking suggest that environmental sources of arylamines in tobacco smoke are the important contributors to the risk of the disease.

Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Nice, France; February 7 - 10, 2004; in poster session 892 (Susceptibility genes).