Abstract
PurposeThe polymorphisms in genes including GSTM1, GSTP1 and GSTT1 have been found to predict development and therapeutic efficacy in various malignancies. Breast cancer is one of most common cancers among women. In this study, we evaluated the prognostic value of three functional polymorphisms of GSTs in patients with previously untreated metastatic breast cancer (MBC).Patients and MethodsThe genotype of GSTT1, GSTP1, and GSTM1 in 170 patients with previously untreated MBC from one single center were assessed via PCR-based RFLP methods. The prognostic of polymorphisms on overall survival (OS) was examined using the Kaplan-Meier estimates and Cox proportional hazard ratio (HR) regression analyses.ResultsThe null genotypes of GSTT1 and GSTM1 were significantly correlated to poor OS compared with the present genotypes, respectively. After adjusting for clinic-pathologic factors, GSTT1 and GSTM1 genetic variants were still significantly associated with OS (HR, 1.92; 95% CI, 1.26-2.91 and HR, 1.53; 95% CI, 1.05-2.23). GSTT1 and GSTM1 were independent survival predictors and GSTP1 was not associated with overall survival of previous untreated MBC.ConclusionThis exploratory analysis suggests that in addition to clinic-pathologic factors, the genetic variants in GSTT1 and GSTM1 might be predictive of survival outcome in patients with previously untreated MBC.
Highlights
Breast cancer is a heterogeneous disease and the most common cancer among women with a drastically increasing rate in China [1]
The null genotypes of glutathione S-transferase mu (GSTT1) and glutathione S-transferase theta (GSTM1) were significantly correlated to poor overall survival (OS) compared with the present genotypes, respectively
After adjusting for clinic-pathologic factors, GSTT1 and GSTM1 genetic variants were still significantly associated with OS (HR, 1.92; 95% confidence interval (CI), 1.26-2.91 and hazard ratio (HR), 1.53; 95% CI, 1.05-2.23)
Summary
Breast cancer is a heterogeneous disease and the most common cancer among women with a drastically increasing rate in China [1]. Despite of significant improvements in the treatment of MBC during the last decade, it still remains an incurable disease with a median overall survival of 18-30 months [3]. Effective chemotherapy drugs used in the treatment of various malignant tumors always result in drug resistance and toxicity. It was reported that many genetic polymorphisms were involved in metabolism enzyme function, drug resistance, toxicity and efficiency of chemotherapy [5,6,7,8,9,10,11]. Hunting for genetic markers to improve clinical outcome of MBC patients becomes a big challenge
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