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

Abstract

BACKGROUNDIt 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.METHODSThe 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.RESULTSAfter 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.CONCLUSIONSThe 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. Cancer 2005. © 2004 American Cancer Society.

GSTT1 and GSTP1 polymorphisms and breast cancer risk: a meta-analysis

“…Out of the 161 abstracts retrieved through the search criteria, 94 were irrelevant, nine articles [35][36][37][38][39][40][41][42][43] were excluded because they were conducted on overlapping populations with other eligible studies [6,8,20,25,30,44,45] (these excluded articles represent smaller studies performed on subsets of larger eligible studies), five studies [46][47][48][49][50] were excluded given that they have not included controls in their study design, two articles [4,51] were reviews/meta-analyses, and three studies [52][53][54] were excluded due to other reasons (two of them [52,53] was excluded due to reporting reasons, i.e. no reporting of the relevant genotype frequencies, whereas the other [54] was excluded for examining the association between GSTA1 polymorphism and survival after breast cancer treatment At the overall analysis, the null GSTT1 genotype was associated with elevated breast cancer risk (pooled OR=1.114, 95%CI: 1.035-1.199, random effects).…”

Polymorphism of XRCC1 predicts overall survival of gastric cancer patients receiving oxaliplatin-based chemotherapy in Chinese population

“…It was in agreement with the previous studies of colorectal and breast cancer. 27,29 However, Goekkurt 30 and Stoehlmacher 31 showed that GSTP1-105 G/G genotype predicted superior survival in gastric cancer patients and colorectal cancer patients, respectively. In this study, GSTP1-105 polymorphism did not play a significant role in the prediction of clinical outcome, perhaps due to the rare number of patients who had the G/G genotype, indicating that ethnic background eliminated race-specific variation in the distribution of genotypes in GSTP1.…”

Predictive Role of Glutathione-S-transferase Gene Polymorphisms in Risk and Prognosis of Hepatocellular Carcinoma

“…Genotypic and phenotypic variation in GST activity has been noted, and is thought to affect risk and prognosis in several cancers (Wiencke et al, 1990;Pemble et al, 1994;Hayes and Pulford, 1995;Dalhoff et al, 2005;Yang et al, 2005;Goekkurt et al, 2006;Reszka et al, 2006;Shiga et al, 2006). The Single nucleotide polymorphisms (SNPs) of GST genes induced the different expression of the gene product, and GSTM1, GSTT1 and GSTP1 genotypes have been hypothesized to affect the risk of HCC (Zhang et al, 2005;White et al, 2008;Giera et al, 2010), and response to chemotherapy (Ott et al, 2008;Tahara et al, 2011).…”