Glutathione S-transferase T1, O1 and O2 polymorphisms are associated with survival in muscle invasive bladder cancer patients.

OBJECTIVE: To 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 METHODS: A 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

Glutathione S-transferase (GST) genotype distribution.

<p>Glutathione S-transferase (GST) genotype distribution.</p

Survival analysis Kaplan–Meier curves according to <i>GSTO2</i> polymorphism for overall mortality (A), as well as mortality of TCC patients on chemotherapy (B).

<p>Survival analysis Kaplan–Meier curves according to <i>GSTO2</i> polymorphism for overall mortality (A), as well as mortality of TCC patients on chemotherapy (B).</p

Patient characteristics at study entry.

<p>Patient characteristics at study entry.</p

<i>GSTT1, GSTP1, GSTO1, GSTO2, GSTM1</i> and <i>GSTA1</i> polymorphisms as the predictors for overall mortality among 101 patients with muscle invasive TCC after 5 yrs of follow-up by the Cox proportional hazards regression.

<p>Abbreviations: CI, Confidence Interval; HR, Hazard Ratio.</p>a<p>Adjusted for age and gender.</p>b<p>Adjusted for the covariates in Model 1 plus an additional adjustment for grade.</p

Survival analysis Kaplan–Meier curves according to <i>GSTO1</i> polymorphism for overall mortality (A), as well as mortality of TCC patients on chemotherapy (B).

<p>Survival analysis Kaplan–Meier curves according to <i>GSTO1</i> polymorphism for overall mortality (A), as well as mortality of TCC patients on chemotherapy (B).</p