GSTM1 and GSTT1 polymorphisms are associated with increased bladder cancer risk: Evidence from updated meta-analysis

Background: Previous studies have indicated association between GSTM1 and GSTT1 gene polymorphisms and bladder cancer susceptibility, but the results have been inconclusive. Here, we performed a meta-analysis to investigate the association between GSTM1/GSTT1 deletion polymorphisms and bladder cancer susceptibility. Methods: We searched for all studies investigating the association between GSTM1 or GSTT1 polymorphism and bladder cancer susceptibility in Pubmed, Web of Knowledge, and the Cochrane Central Search Library. A systematic review and meta-analysis were performed. Subgroup analyses were performed on different ethnicity, population-based and smoking status. Results: Our search identified 63 studies. GSTM1 null, GSTT1 null and GSTM1/GSTT1 double-null genotypes were associated with increased risk of bladder cancer (OR: 1.36 95% CI: 1.25-1.47, P<0.01; OR: 1.13 95% CI: 1.02-1.25, P<0.01; OR: 1.84 95% CI: 1.50-2.26, P<0.01). Subgroup analyses indicated that the GSTM1-null genotype was associated with increased risk of bladder cancer in Caucasians and Asians, while the GSTT1-null genotype was associated with increased risk of bladder cancer in Caucasians. The GSTM1/GSTT1 double-null genotype was associated with increased risk of bladder cancer in Caucasians, Asians, and Africans. Stratified analyses of population-based associations indicated increased bladder cancer risk associated with GSTM1-null and GSTM1/GSTT1 double-null genotypes in hospital-based and population-based studies. GSTM1 deletion was associated with increased bladder cancer risk in both smokers and nonsmokers. Non-smokers with the GSTM1/GSTT1 double-null genotype had an increased bladder cancer risk. Conclusion: This meta-analysis demonstrates that the GSTM1-null, GSTT1-null, and GSTM1/GSTT1 double-null genotypes are associated with increased bladder cancer risk.