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.
Highlights
Breast cancer is the common cancer and one of the leading causes of death among women worldwide, including Thailand
The deletion polymorphisms of GSTM1 and GSTT1 genes are associated with reduced enzyme activity that influenced clinical outcomes of chemotherapeutic agents in breast cancer
The deletion polymorphisms of GSTM1 and GSTT1 genes are associated with reduced enzyme activity that could be associated with the susceptibility to breast cancer and treatment outcome (Zhang et al, 2017)
Summary
Breast cancer is the common cancer and one of the leading causes of death among women worldwide, including Thailand. In 2018, the GLOBOCAN project reported that there were 2,088,849 new cases and 626,679 deaths of breast cancer among women worldwide (Bray et al, 2018). In Thailand, according to the National Cancer Institute (NCI)’ s report, breast cancer was the most leading new cancer among Thai women follow by cervix uteri cancer in 2015 (Imsamran et al.,2015). GSTM1 and GSTT1 enzymes catalyze the conjugation of glutathione to electrophilic compounds, resulting in less reactive and more immediately for excretion. The deletion polymorphisms of GSTM1 and GSTT1 genes are associated with reduced enzyme activity that could be associated with the susceptibility to breast cancer and treatment outcome (Zhang et al, 2017). Because of the limited information regarding GSTM1 and GSTT1 polymorphisms among Thai patients with breast cancer, the objective of this research is to explore the frequency and association between these two genetic polymorphisms on survival in Thai patients with breast cancer
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