Abstract
ObjectiveTo examine the association of six glutathione transferase (GST) gene polymorphisms (GSTT1, GSTP1/rs1695, GSTO1/rs4925, GSTO2/rs156697, GSTM1, GSTA1/rs3957357) with the survival of patients with muscle invasive bladder cancer and the genotype modifying effect on chemotherapy.Patients and MethodsA total of 105 patients with muscle invasive bladder cancer were included in the study. The follow-up lasted 5 years. The effect of GSTs polymorphisms on predicting mortality was analyzed by the Cox proportional hazard models, while Kaplan-Meier analysis was performed to assess differences in survival.Results GSTT1 active, GSTO1 Asp140Asp or GSTO2 Asp142Asp genotypes were independent predictors of a higher risk of death among bladder cancer patients (HR = 2.5, P = 0.028; HR = 2.9, P = 0.022; HR = 3.9, P = 0.001; respectively) and significantly influenced the overall survival. There was no association between GSTP1, GSTM1 and GSTA1 gene variants with overall mortality. Only GSTO2 polymorphism showed a significant effect on the survival in the subgroup of patients who received chemotherapy (P = 0.006).Conclusion GSTT1 active genotype and GSTO1 Asp140Asp and GSTO2 Asp142Asp genotypes may have a prognostic/pharmacogenomic role in patients with muscle invasive bladder cancer.
Highlights
Glutathione transferases (GST) are detoxification enzymes that play a role in the conjugation of endogenous or exogenous xenobiotic toxins to glutathione (GSH), several GSTs function as GSH peroxidases [1]
There was no association between GSTP1, GSTM1 and GSTA1 gene variants with overall mortality
Polymorphic expression of GSTA1, GSTM1 and GSTO1 influences the risk of transitional cell carcinoma (TCC) of urinary bladder [2,3]
Summary
Glutathione transferases (GST) are detoxification enzymes that play a role in the conjugation of endogenous or exogenous xenobiotic toxins to glutathione (GSH), several GSTs function as GSH peroxidases [1]. The family of cytosolic GSTs has different classes including the Alpha (GSTA), Mu (GSTM), Pi (GSTP), Omega (GSTO) and Theta (GSTT) class [1]. Polymorphic expression of GSTA1, GSTM1 and GSTO1 influences the risk of transitional cell carcinoma (TCC) of urinary bladder [2,3]. Up-regulated GST activity is a hallmark of a malignant phenotype of TCC and is considered important to maintain a prooxidantantioxidant balance towards a more reduced state in the course of progression of these tumors [4]. Enzymatic activity of GST proteins might influence the capacity of several drugs, used in the treatment of TCC patients, to evoke tumor cell death. It is reasonable to assume that common GST polymorphisms may have a prognostic and/or pharmacogenomic role in TCC patients, especially in the case of muscle invasive tumors
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
