GSTM1 AND GSTT1 GENES ARE POTENTIAL RISK MODIFIERS FOR BLADDER-CANCER

The role of the polymorphic glutathione S-transferase genes GSTM1 and GSTT1 in the development and in the clinicopathological outcome of bla dder cancer was investigated in 37 Egyptian bladder cancer patients an d 34 matched controls. Of the 37 patients Studied, 26 had transitional cell carcinoma (TCC) and 11 had squamous cell carcinoma (SCC). Fourte en out of twenty-six TCC and four out of eleven SCC patients were infe cted with schistosoma. We observed an increased relative risk for blad der cancer associated with the GSTM1 null,genotype (OR = 2.99; 95% CL = 1.01-9.00;p = 0.02). The relative risk was more pronounced in squamo us cell carcinoma (SCC) (OR = 5.70; 95% CL := 0.91-36.70; p = 0.03) th an in transitional cell carcinoma (TCC) (OR = 2.39; 95% CL = 0.73-7.90 ; p = 0.08). Our results also indicate that the GSTT1 polymorphism is individually associated with increased risk for bladder cancer (OR = 4 .93; 95% CL : 1.39-18.42; p = 0.004) with no preferential increase in risk with respect to the type of the carcinoma. Individuals with the n ull genotype for both GSTM1 and GSTT1 were at a significantly higher r isk for developing bladder cancer than individuals with both genes pre sent (OR = 9.92; 95% CL = 1.84-46.90; p = 0.001). These individuals we re more susceptible to developing SCC than TCC (OR = 14.16; 95% CL = 1 .35-131.35; p = 0.01; and OR = 8.5; 95% CL = 1.38-60.10; p = 0.007, re spectively). In conclusion, our results indicate that the null genotyp es for GSTM1 and GSTT1, either individually or in combination, are imp ortant host risk factors for bladder cancer. In addition, the null GST M1 genotype may also affect the clinicopathological tumor outcome. Sin ce the deleted genotypes for GSTM1 and GSTT1 are prevalent in the gene ral population, the identification of these individuals may provide a useful public health approach for early detection and prevention of en vironmental cancers.