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 polymorphisms in the GSTM1, 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 105Val 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.
Yang
Gong
G
Vanderbilt Center for Health Services Research, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232-8300, USA. gong.yang@vanderbilt.edu
Shu
Xiao-Ou
XO
Ruan
Zhi-Xian
ZX
Cai
Qiu-Yin
QY
Jin
Fan
F
Gao
Yu-Tang
YT
Zheng
Wei
W
D000217:Acyltransferases / Q000235:genetics*; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D002277:Carcinoma / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D016022:Case-Control Studies; D005260:Female; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D011110:Polymorphism, Genetic; D012307:Risk Factors; D016019:Survival Analysis; D016896:Treatment Outcome
D000217:Acyltransferases; D005982:Glutathione Transferase; C413545:glutathione S-transferase T1; C043403:fatty acyl ethyl ester synthase