Glutathione S-transferase polymorphisms influence chemotherapy response and treatment outcome in breast cancer

Genet Mol Res. 2015 Sep 22;14(3):11126-32. doi: 10.4238/2015.September.22.6.

Abstract

The aim of this study was to evaluate the role of GSTM1 null/present, GSTT1 null/present, and GSTP1 IIe105Val polymorphisms in the clinical response to chemotherapy and treatment outcome of patients with breast cancer. A total of 262 subjects were randomly selected from among patients with a histologically confirmed breast cancer. The genotypes of GSTM1, GSTT1, and GSTP1 IIe105Val polymorphisms were determined by polymerase chain reaction-restriction fragment length polymorphism analysis. Our study found that the null genotype of GSTM1 was associated with a better response to chemo-therapy, and the odds ratio [95% confidence interval (CI)] was 1.78 (1.03-3.08). In the Cox proportional hazard model, the hazard ratio (95%CI) for overall survival (OS) in patients carrying the null genotype of GSTM1 was 0.57 (0.32-0.98) using the non-null genotype as the reference variable. However, we observed no significant association between the GSTT1 and GSTP1 polymorphisms and response to chemotherapy and OS in patients with breast cancer. In conclusion, our study found that the GSTM1 polymorphism plays an important role in influencing the chemotherapy response and OS in patients with breast cancer.

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / pharmacology
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / mortality
  • Docetaxel
  • Female
  • Genetic Association Studies
  • Glutathione S-Transferase pi / genetics*
  • Glutathione Transferase / genetics*
  • Humans
  • Kaplan-Meier Estimate
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Proportional Hazards Models
  • Taxoids / administration & dosage
  • Thiotepa / administration & dosage
  • Treatment Outcome

Substances

  • Taxoids
  • Docetaxel
  • Thiotepa
  • glutathione S-transferase T1
  • GSTP1 protein, human
  • Glutathione S-Transferase pi
  • Glutathione Transferase
  • glutathione S-transferase M1