Genetic Variation in Glutathione S-Transferase genes: GSTM1, GSTT1, and GSTP1 with Bladder Cancer Susceptibility
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Over the past decade, more research has been dedicated to studying the relationship between arsenic9induced health conditions and the ingestion of inorganic arsenic at low to moderate concentration levels from contaminated household drinking supplies. Among the genes that are involved in the detoxification of carcinogens such as inorganic arsenic are the Glutathione S9 Tranferase (GST) family of genes. Genes in this family are suspected to be important in the methylation and clearance of arsenic. Polymorphisms in GSTM1, GSTT1 and GSTP1 alter their function in metabolizing arsenic, which may play a role in the susceptibility to arsenic9induced cancer. The aims of this study were to estimate the risk associated with polymorphisms in these three genes with bladder cancer risk as well as to explore interactions between genes and arsenic exposure with bladder cancer. The single nucleotide polymorphism (SNP) rs1695 in GSTP1 was genotyped using a Taqman-based approach using DNA from 198 bladder cancer cases and 248 controls participating in a case-control study in Southeastern Michigan. Arsenic exposure was measured using household water samples and past residential history, geocoded and predicted from multiple sources. Through PCR9based analysis, GSTM1 and GSTT1 were genotyped from subject DNA samples. We observed a 31% reduction (OR=0.69; 95% CI= 0.4691.03) in the odds of bladder cancer associated with the rs1695 SNP in GSTP1, however no evidence for interaction was observed between rs1695 polymorphism in GSTP1 and arsenic exposure on bladder cancer risk. For subjects with a GSTM1 deletion, smokers had a 77% risk increase (OR=1.77; 95% CI= 0.6592.51) compared to non-smokers (OR=0.65; 95% CI= 0.2291.95). However, results indicate that smoking subjects with a GSTT1 deletion had a reduced risk of bladder cancer when compared to non9 smokers (OR=0.87; 95% CI=0.5691.37 and OR=1.64; 95% CI=0.8093.34, respectively). Both GSTM1 and GSTT1 show no statistical relationship with increased risk of bladder cancer. We propose that larger studies in populations exposed to moderate levels of arsenic are warranted in order to further clarify the relationships between these genes.