Abstract
BackgroundPrevious 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.MethodsWe 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.ResultsOur 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.ConclusionThis meta-analysis demonstrates that the GSTM1-null, GSTT1-null, and GSTM1/GSTT1 double-null genotypes are associated with increased bladder cancer risk.
Highlights
Bladder cancer is the ninth most common malignancy worldwide, and the fourth most common malignancy in the United States [1, 2]. 70% of bladder cancers are nonmuscle invasive, whereas the remaining 30% are muscle invasive bladder cancers [3]
46 studies described the relationship between GSTM1 polymorphism and bladder cancer susceptibility, involving 28270 individuals
The pooled meta-analysis showed that the GSTM1 null genotype was associated with increased risk of bladder cancer
Summary
Bladder cancer is the ninth most common malignancy worldwide, and the fourth most common malignancy in the United States [1, 2]. 70% of bladder cancers are nonmuscle invasive, whereas the remaining 30% are muscle invasive bladder cancers [3]. Only a small percentage of people develop bladder cancer after exposure to these environmental factors, indicating that genetic susceptibility plays an important role in bladder cancer development. Glutathione S-transferases (GSTs) are members of a multigene family of phase II enzymes, which are involved in the detoxification of various carcinogens, and have been recognized as an important factor in bladder cancer development [5]. Previous meta-analyses have indicated an association of GSTM1 and GSTT1 deletion polymorphisms with increased bladder cancer risk [9–11]; the results have been inconsistent. We performed an updated meta-analysis to investigate the association between GSTM1/GSTT1 deletion polymorphisms and bladder cancer susceptibility. Previous studies have indicated association between GSTM1 and GSTT1 gene polymorphisms and bladder cancer susceptibility, but the results have been inconclusive. We performed a meta-analysis to investigate the association between GSTM1/GSTT1 deletion polymorphisms and bladder cancer susceptibility
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