GSTM1, GSTT1 Null Variants, and GPX1 Single Nucleotide Polymorphism Are Not Associated with Bladder Cancer Risk in Egypt

Abstract

Bladder cancer is the most common male malignancy in Egypt, consists predominantly of urothelial cell carcinoma (UCC) and squamous cell carcinoma (SCC), and disparities in incidence exist between men and women regardless of geographic region. Tobacco smoke exposure and Schistosoma haematobium (SH) infection and the presence of GSTM1, GSTT1, and GPX1 genotypes, as modulators of the carcinogenic effect of reactive oxidative species, were hypothesized to modify bladder cancer risk and possibly explain these gender differences. We evaluated the association between bladder cancer risk and functional polymorphisms in the GSTM1, GSTT1, and GPX1 genes in 625 cases and 626 matched population-based controls in Egypt and assessed for potential interactions between these candidate genes and environmental exposures, such as smoking and SH infection. We analyzed the risk for developing UCC and SCC separately. None of these functional polymorphisms were significantly associated with bladder cancer risk. There were no significant interactions between genotypes and smoking or SH infection in this population, nor was any difference detected in genotypic risk between men and women. Our findings suggest that common genetic variations in GSTM1, GSTT1, and GPX1 are not associated with bladder cancer risk overall and that well-known environmental risk factors, such as smoking and SH infection, do not interact with these genes to modulate the risk. Our data indicate that common genetic variations in GSTM1, GSTT1, and GPX1 were not associated with bladder cancer risk.