Genetic polymorphisms in glutathione-S-transferase genes (GSTM1, GSTT1, GSTP1) and survival after chemotherapy for invasive breast carcinoma

BACKGROUND. it has been suggested that genetic polymorphisms in certain glutathione-S-transferase (GST) genes reduce the effectiveness of detoxifying cytotoxins generated by chemotherapeutic agents, potentially resulting in enhanced clinical responses to chemotherapy. METHODS. The authors evaluated common polymorphisins in the GSTAM1, GSTT1, and GSTP1 genes for associations with overall survival in 1034 patients with invasive breast carcinoma who were recruited into the Shanghai Breast Cancer Study between 1996 and 1998, treated with chemotherapy, and followed for a median of 5.3 years. RESULTS. After adjusting for age, tumor stage, and the use of radiotherapy and tamoxifen, women who were homozygous for the variant GSTP1 (115)Val allele had a 60% reduction in mortality risk compared with women who were homozygous for the Ile allele (hazard ratio, 0.4; 95% confidence interval, 0.2-0.8). No association was found with respect to any of the GSTM1 or GSTT1 genotypes. CONCLUSIONS. The results of the current study indicate a potential role for GSTP1 polymorphism in predicting the clinical outcomes of patients with breast carcinoma who are treated with chemotherapy. (C) 2004 American Cancer Society.