Abstract
BackgroundThe glutathione S-transferases (GSTs) are a superfamily of phase II detoxifying enzymes that inactivates a wide variety of potential carcinogens through glutathione conjugation. Polymorphic changes in the GST genes have been reported to be associated with increased susceptibility to cancer development and anticancer drug resistance. In this study, we investigated the association between genetic variants in GSTM1 and GSTP1 and patients’ clinicopathological parameters. The prognostic values of such associations were evaluated among bladder cancer patients.MethodsGenotyping of GSTM1 and GSTP1 in bladder cancer patients was assessed using polymerase chain reaction followed by DNA sequencing. Overall survival was estimated using the Kaplan-Meier method and multiple logistic regression and correlation analysis were performed.ResultsThe GSTM1 null genotype was significantly associated with poor overall survival compared with the wild-type GSTM1 genotype. There was a trend towards better overall survival in patients with wild-type GSTP1 allele (AA) compared with GSTP1 (AG/GG) genotype. Interestingly, Kaplan-meier survival curve for GSTM1 null patients adjusted for sub-cohort with amplified HER2 gene showed poor survival compared with the GSTM1 null/ non-amplified HER2 gene. Also the same population when adjusted with HER2 protein expression, data showed poor survival for patients harboring GSTM1 null/high HER2 protein expression compared with low protein expression.ConclusionThis study focuses on the impact of GSTM1 null genotype on bladder cancer patients’ outcome. Further investigations are required to delineate the underlying mechanisms of combined GSTM−/− and HER2 status in bladder cancer.
Highlights
The glutathione S-transferases (GSTs) are a superfamily of phase II detoxifying enzymes that inactivates a wide variety of potential carcinogens through glutathione conjugation
The present study revealed that Glutathione STransferase mu (GSTM1) null genotype is significantly associated with poor overall survival in urinary bladder cancer patients
Combined GSTM1 deletion and amplified Human Epidermal growth factor Receptor 2 (HER2) gene might be considered as the worse prognostic genotype combination in bladder cancer
Summary
The glutathione S-transferases (GSTs) are a superfamily of phase II detoxifying enzymes that inactivates a wide variety of potential carcinogens through glutathione conjugation. Polymorphic changes in the GST genes have been reported to be associated with increased susceptibility to cancer development and anticancer drug resistance. It has been estimated that around 550,000 new bladder cancer cases and 199,922 deaths occurred in the year 2018 worldwide and these numbers are expected to double in the upcoming years [1]. It is well documented that occupational exposure to chemical carcinogens including aromatic amines and polycyclic aromatic hydrocarbons is associated with the risk of bladder cancer development [2, 4]. Kellen et al reported an increased risk of developing bladder cancer associated with cumulative exposure to aromatic amines, but not to PAHs and diesel [5]. Ferrís et al concluded that bladder cancer is a result of the interaction between constitutional and environmental risk factors including aromatic amines and polycyclic aromatic
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