Frequency and Association Of GSTM1 and GSTT1 Gene Polymorphisms with Survival in Breast Cancer Patients

Abstract

Objective: Glutathione S-transferase M1 and T1 (GSTM1 and GSTT1) are the key detoxification enzymes of xenobiotics, including chemotherapeutic drugs. The deletion polymorphisms of GSTM1 and GSTT1 genes are associated with reduced enzyme activity that influenced clinical outcomes of chemotherapeutic agents in breast cancer. However, there is limited information among Thai patients. This research aims to explore the frequency and role of GSTM1 and GSTT1 polymorphisms on survival among Thai patients with breast cancer. Methods: The retrospective cohort study was performed. Demographic data and clinicopathology characteristics were collected from hospital base registry data and medical records. A multiplex qualitative real-time PCR method was used to detect the presence or absence of the GSTM1 and GSTT1 gene in the genomic DNA samples of the participants. Results: The frequencies of the GSTM1 and GSTT1 null genotypes in 198 breast cancer patients were 65.70% and 33.30%, respectively. The overall survival at 1, 3 and 5 years were 95.00%, 83.00%, 71.00% respectively. The log rank test and Cox proportional hazards revealed a significant different in the 5-years overall survival according to lymph node metastasis and tumor stage (P = 0.014 and P < 0.001). No associations between overall survival and GSTM1 or GSTT1 genotype were found in single or combined genotypes analyses (P = 0.76 and P= 0.15). Conclusion: The results of our study provided the epidemiological information for prognostic of survival in breast cancer patients treated with chemotherapy.

Redox proteome analysis of auranofin exposed ovarian cancer cells (A2780)

“…Glutathione transferases (GSTs) are also involved in metal detoxification and drug cell resistance by favoring their conjugation to GSH [ 57 ]. The two key chemotherapeutic drugs' detoxification agents [ 58 ] GSTT1 and MGST1 were upregulated. As for the thioredoxin pathway, we did not detect significant changes in the expression profiles of glutaredoxins (GLRXs) and glutathione peroxidases (GPXs), while we detected an increased level of Glutathione Reductase (GSR) that plays a role similar to TrxR in the GSH pathway and of S -nitrosoglutathione reductase (GSNOR, also called Alcohol Dehydrogenase 5, ADH5).…”