GSTP1, GSTM1, and GSTT1 polymorphisms as predictors of response to chemotherapy in patients with breast cancer: a meta-analysis

Abstract

Several studies have investigated the effects of polymorphisms in the GSTP1, GSTT1, and GSTM1 genes on responsiveness to chemotherapy in breast cancer, but the results have been inconsistent. The aim of this study was to determine the association between polymorphisms of GSTP1, GSTT1, and GSTM1 genes and response to chemotherapy in patients with breast cancer. The relevant studies were retrieved from PubMed, Embase, ISI Web of Knowledge, China National Knowledge Infrastructure, and Wanfang databases. The articles evaluating the correlations between response to chemotherapy and GSTP1, GSTT1, and GSTM1 polymorphisms in breast cancer patients were comprehensively reviewed. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated to measure the strength of the associations. These associations were assessed with the χ ² test in this meta-analysis. Subgroup analysis by chemotherapy protocol and ethnicity were conducted to explore the source of heterogeneity among studies. A total of 14 articles with 31 studies involving GSTP1, GSTT1, and GSTM1 polymorphisms with response to chemotherapy were identified in the final meta-analysis. In the overall analysis, a significant association of GSTM1-present/GSTM1-null polymorphism with responsiveness to chemotherapy was observed in breast cancer patients (OR 0.74, CI 0.60–0.92, P = 0.006), whereas the GSTT1-present/GSTT1-null and GSTP1rs1695 polymorphisms were not significantly associated with clinical response to chemotherapy. The subgroup analysis by chemotherapy protocol indicated that the patients who harboring GSTP1rs1695 AA or AG variant had a higher response rate to anthracycline-based chemotherapy than those carrying GSTP1rs1695 GG variant [AA vs. GG: OR 0.48, CI 0.29–0.80, P < 0.05; AA vs. AG: OR 0.60, CI 0.43–0.83, P < 0.05; A vs. G: OR 0.60, CI 0.47–0.77, P < 0.05; AA vs. (AG + GG): OR 0.56, CI 0.42–0.76, P < 0.05; (AA + AG) vs. GG: OR 0.57, CI 0.34–0.94, P < 0.05]. In addition, the heterogeneity existed among studies for GSTP1 polymorphism, while no obvious heterogeneity was detected for GSTT1 and GSTM1 polymorphisms. And the heterogeneity present in different studies, evaluating the association of GSTP1 polymorphism with response to anthracycline-based chemotherapy, disappeared in breast cancer patients after subgroup analysis by chemotherapy regimen was performed. In conclusion, this meta-analysis suggested that GSTP1rs1695 and GSTM1-present/GSTM1-null polymorphisms could be considered as reliable predictors of response to anthracycline-based chemotherapy in patients with breast cancer.

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