Abstract
BackgroundFourteen previous meta-analyses have been published to analyze the polymorphisms of individual GSTM1 present/null, GSTT1 present/null, and GSTP1 IIe105Val on breast cancer (BC) risk. However, their meta-analyses did not explore the combined effects of the three genetic polymorphisms on BC risk. In addition, they did not evaluate the credibility of statistically significant associations. Furthermore, a multitude of new articles have been published on these themes, and therefore a meta-analysis and re-analysis of systematic previous meta-analyses were performed to further explore these issues.ObjectivesTo determine the association between the individual and combined effects of GSTM1, GSTT1, and GSTP1 polymorphisms on breast cancer risk.MethodsCrude odds ratios (ORs) and their 95% confidence intervals (CIs) were applied to estimate the association between individual and combined effects of GSTM1, GSTT1, and GSTP1 polymorphisms on BC risk. To evaluate the credibility of statistically significant associations in the current and previous meta-analyses, we applied the the false-positive report probabilities (FPRP) test and the Venice criteria.Results101 publications were selected to evaluate the individual and combined effects of GSTM1, GSTT1 and GSTP1 polymorphisms on BC risk. Overall, statistically significant elevated BC risk was found in any individual and combined effects of GSTM1 present/null, GSTT1 present/null, and GSTP1 IIe105Val polymorphisms. However, when we restricted studies only involving with high-quality, matching, HWE, and genotyping examination performed blindly or with quality control, significantly increased BC risk was only found in overall population for GSTM1 null genotype, among all populations, Caucasians, and postmenopausal women for the combined effects of GSTM1 and GSTT1 polymorphisms, and in overall analysis for the combined effects of GSTM1, GSTT1, and GSTP1 IIe105Val polymorphisms. Further, less-credible positive results were identified when we evaluated the credibility of positive results of the current and previous meta-analyses.ConclusionsThis meta-analysis indicates that the individual and combined effects of GSTM1, GSTT1 and GSTP1 polymorphisms may be not associated with increased BC risk.
Highlights
Breast cancer (BC) is one of the most common diseases and an important public health challenge among women worldwide, the incidences of breast cancer (BC) are not the same in different countries and ethnic groups [1, 2]
GSTM1, GSTT1, and GSTP1 polymorphisms on breast cancer risk involving with high-quality, matching, Hardy-Weinberg equilibrium (HWE), and genotyping examination performed blindly or with quality control, significantly increased BC risk was only found in overall population for GSTM1 null genotype, among all populations, Caucasians, and postmenopausal women for the combined effects of GSTM1 and GSTT1 polymorphisms, and in overall analysis for the combined effects of GSTM1, GSTT1, and GSTP1 IIe105Val polymorphisms
Lesscredible positive results were identified when we evaluated the credibility of positive results of the current and previous meta-analyses. This meta-analysis indicates that the individual and combined effects of GSTM1, GSTT1 and GSTP1 polymorphisms may be not associated with increased BC risk
Summary
Breast cancer (BC) is one of the most common diseases and an important public health challenge among women worldwide, the incidences of BC are not the same in different countries and ethnic groups [1, 2]. Five classes of GST enzymes have been found (α,μ,π,σ, andθ) [12] and each class is encoded by an independent gene or family genes (such as GSTA, GSTM, GSTP, GSTO, and GSTT genes) Among these genes, both GSTM1 and GSTT1 genes show deletion polymorphisms (null genotype) [13, 14], which cause the absence of expression and enzyme activity loss [15]. Fourteen previous meta-analyses have been published to analyze the polymorphisms of individual GSTM1 present/null, GSTT1 present/null, and GSTP1 IIe105Val on breast cancer (BC) risk. Their meta-analyses did not explore the combined effects of the three genetic polymorphisms on BC risk. A multitude of new articles have been published on these themes, and a meta-analysis and re-analysis of systematic previous meta-analyses were performed to further explore these issues
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