Modifying Effect of Smoking on GSTM1 and NAT2 in Relation to the Risk of Bladder Cancer in Mongolian Population: A Case-Control Study

OBJECTIVES: Tobacco smoking is the predominant risk factor for bladder cancer as it contains cancer-causing chemicals. However, genetic factors may play important role in response towards chemical carcinogens. In this study we aim to investigate genetic polymorphisms of glutathione S-transferase M1 (GSTM1) and N-acetyltransferase 2 (NAT2) as determinants of bladder cancer risk, independently and in combination with tobacco use in the Mongolian population. MATERIALS AND METHODS: The current study was a hospital-based case-control study including 60 histologically confirmed bladder cancer patients and 60 cancer-free controls. PCR-RFLP assay was used to determine the presence of GSTM1 and NAT2 polymorphisms in bladder cancer patients and controls. GSTM1 and NAT2 were tested using binary logistical regression analysis with adjustment or stratification according to the smoking. RESULTS: There were 46 men and 14 women diagnosed with bladder cancer, with mean age was 58±4. The controls included 37 men and 23 women with a mean age of 57±3. The frequency of GSTM1 null genotype was higher in controls (71.67%) than in bladder cancer patients (58.33%) without statistical significance (OR=0.5534; 95% CI=0.2586-1.1843), (p=0.128). The NAT2 low acetylator phenotype was more common in patients with bladder cancer (15%) than in controls (5%). Furthermore, individuals with NAT2 low acetylator phenotype had a nearly 3.35-fold increased risk to develop bladder cancer (OR=3.35; 95% CI=0.8604-13.0657), (p=0.081) while the risk was even higher when combined with null GSTM1 genotype (OR=4; 95% CI=0.4459-37.5308), (p=0.213) but there was no statistical significance. Prevalence of smoking in bladder cancer patients was higher than controls and increased significantly the risk of bladder cancer (OR=8.31; 95% CI=3.66-18.88). Smokers with GSTM1 null genotype were at 5-fold higher risk of bladder cancer (OR=5.0; 95% CI=1.55-16.16), (p=0.007) while NAT2 low acetylator phenotype increased bladder cancer risk by 20-fold (OR=20.5; 95% CI=2.33-80.86), (p=0.006). CONCLUSION: The current study shows that tobacco smokers with the NAT2 low acetylator phenotype and GSTM1 null genotype have the highest risk of bladder cancer in the Mongolian population.