Department of Galactophore, Heping Hospital Affiliated to Changzhi Medical College, Shanxi, Changzhi, China.
Department of Radiotherapy, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
PLoS One. 2020 Mar 10;15(3):e0216147. doi: 10.1371/journal.pone.0216147. eCollection 2020.
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. 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.
To determine the association between the individual and combined effects of GSTM1, GSTT1, and GSTP1 polymorphisms on breast cancer risk.
Crude 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.
101 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.
This meta-analysis indicates that the individual and combined effects of GSTM1, GSTT1 and GSTP1 polymorphisms may be not associated with increased BC risk.
先前已有 14 项荟萃分析研究了 GSTM1 纯合缺失型、GSTT1 纯合缺失型和 GSTP1 IIe105Val 三种基因多态性与乳腺癌（BC）风险之间的关系。然而，这些荟萃分析并未探讨三种遗传多态性联合作用对 BC 风险的影响，也未评估有统计学意义关联的可信度。此外，关于这些主题的大量新文章已经发表，因此对先前的系统荟萃分析进行了荟萃分析和再分析，以进一步探讨这些问题。
确定 GSTM1、GSTT1 和 GSTP1 多态性的个体和联合作用与乳腺癌风险之间的关系。
采用粗比值比（OR）及其 95%置信区间（CI）来估计 GSTM1、GSTT1 和 GSTP1 多态性的个体和联合作用与 BC 风险之间的关系。为了评估当前和先前荟萃分析中具有统计学意义关联的可信度，我们应用了假阳性报告概率（FPRP）检验和威尼斯标准。
选择了 101 项出版物来评估 GSTM1、GSTT1 和 GSTP1 多态性对 BC 风险的个体和联合作用。总体而言，在 GSTM1 存在/缺失、GSTT1 存在/缺失和 GSTP1 IIe105Val 多态性的任何个体和联合作用中，均发现乳腺癌风险显著升高。然而，当我们仅将研究限制在涉及高质量、匹配、HWE 和进行盲法或具有质量控制的基因分型检查的研究时，仅在总体人群中发现 GSTM1 缺失基因型与乳腺癌风险显著增加，在所有人群、白种人和绝经后妇女中发现 GSTM1 和 GSTT1 多态性的联合作用与乳腺癌风险显著增加，在 GSTM1、GSTT1 和 GSTP1 IIe105Val 多态性的联合作用分析中发现乳腺癌风险显著增加。此外，当我们评估当前和先前荟萃分析中阳性结果的可信度时，发现了可信度较低的阳性结果。
本荟萃分析表明，GSTM1、GSTT1 和 GSTP1 多态性的个体和联合作用可能与乳腺癌风险的增加无关。
