The relationship between GSTA1, GSTM1, GSTP1, and GSTT1 genetic polymorphisms and bladder cancer susceptibility: A meta-analysis

Medicine (Baltimore). 2016 Sep;95(37):e4900. doi: 10.1097/MD.0000000000004900.

Abstract

Background: Previous studies have investigated the relationship between GSTA1, GSTM1, GSTP1, and GSTT1 polymorphisms and bladder cancer (BCa) susceptibility, respectively, but the results remain inconsistent. So, we conducted this meta-analysis including 79 case-control studies to explore such relationships.

Methods: We searched PubMed, EMBASE, Cochrane library, Web of Science, and CNKI for relevant available studies. The pooled odds ratios (ORs) with 95% confidence intervals (CIs) were implemented to evaluate the intensity of associations. Publication bias was estimated using Begg funnel plots and Egger regression test. To assess the stability of the results, we used sensitivity analysis with the method of calculating the results again by omitting 1 single study each time. Between-study heterogeneity was tested using the I statistic.

Results: No significant association between GSTA1 polymorphism and BCa susceptibility (OR = 1.05, 95% CI 0.83-1.33) was noted. Besides, meaningful association between individuals who carried the GSTM1 null genotype and increased BCa risk was detected (OR = 1.39, 95%CI 1.28-1.51). When stratified by ethnicity, significant difference was found in both Caucasian (OR = 1.39, 95% CI 1.23-1.58) and Asian populations (OR = 1.45, 95% CI 1.31-1.61). Moreover, in the subgroup analysis by source of controls (SOC), the results were significant in both hospital-based control groups (OR = 1.49, 95% CI 1.35-1.64) and population-based control groups (OR = 1.21, 95% CI = 1.07-1.37). Additionally, the analysis revealed no significant association between GSTP1 polymorphism and BCa risk (OR = 1.07, 95% CI 0.96-1.20). What is more, significant associations between GSTT1 polymorphism and BCa susceptibility were discovered (OR = 1.11, 95% CI 1.00-1.22). In the subgroup analysis by ethnicity, significant associations between GSTT1 null genotype and BCa risk were observed only in Caucasians (OR = 1.25, 95% CI 1.09-1.44). Furthermore, when stratified by SOC, no obvious relationship was found between the GSTT1 null genotype polymorphism with hospital-based population (OR = 1.11, 95% CI 0.97-1.28) or population-based population (OR = 1.10, 95% CI 0.96-1.27).

Conclusion: This study suggested that GSTM1 null genotype and GSTT1 null genotype might be related to higher BCa risk, respectively. However, no associations were observed between GSTA1 or GSTP1 polymorphisms and BCa susceptibility.

Publication types

  • Meta-Analysis

MeSH terms

  • Genetic Predisposition to Disease
  • Glutathione S-Transferase pi / genetics*
  • Glutathione Transferase / genetics*
  • Humans
  • Urinary Bladder Neoplasms / genetics*

Substances

  • glutathione S-transferase T1
  • GSTA1 protein, human
  • GSTP1 protein, human
  • Glutathione S-Transferase pi
  • Glutathione Transferase
  • glutathione S-transferase M1