Effects of glutathione S-transferase (GST) M1 and GSTT1 genotypes on urothelial cancer risk

The M1 member of the mu class of the glutathione S-transferase (GSTM1) gene is present in about 50% of individuals. GSTT1, a member of the theta class, which has been recently shown to be polymorphic, is expressed in 35–90% of individuals. In this study, 145 Japanese patients with urothelial transitional cell carcinoma and 145 healthy controls, frequency-matched for age and gender, were compared for frequencies of GSTM1 and GSTT1 genotypes. The urothelial cancer risk increased due to the GSTM1 null genotype (odds ratio (OR) 1.71, 95% confidence interval (CI) 1.05–2.79). On the other hand, the OR tended to decrease due to the GSTT1 null genotype, although not significantly. Among individuals of the GSTM1 null genotype, those of the GSTT1-positive genotype had a two-fold risk (OR 2.62, 95% CI 1.36–5.05) compared with the GSTT1 null genotype (OR 1.25, 95% CI 0.62–2.51). A significant interaction between the GSTM1 genotype and smoking status was found; the GSTM1 null genotype was associated with an increased risk of urothelial cancer among smokers (OR 1.98, 95%CI 1.10–3.57).