Glutathione S-Transferase T1, O1 and O2 Polymorphisms Are Associated with Survival in Muscle Invasive Bladder Cancer Patients

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.

Role of GSTM1, GSTT1, and GSTP1 IIe105Val gene polymorphisms in the response to chemotherapy and overall survival of advanced non-small cell lung cancer

“…Many previous epidemiological studies have reported that GSTs may affect the efficacy of chemotherapy on cancer (Djukic et al, 2013;Duggan et al, 2013;Oliveira et al, 2014;Kap et al, 2014;Goričar et al, 2015). Djukic et al (2013) reported that the GSTT1 active genotype was associated with the prognosis of patients with muscle invasive bladder cancer in a Serbian population.…”

“…Djukic et al (2013) reported that the GSTT1 active genotype was associated with the prognosis of patients with muscle invasive bladder cancer in a Serbian population. Duggan et al (2013) conducted a study in an American population with breast cancer and found that the GSTP1 IIe105Val gene polymorphism increased the risk of all-cause mortality in breast cancer survivors.…”

Glutathione S-transferase polymorphisms influence chemotherapy response and treatment outcome in breast cancer

“…An increasing number of studies have investigated the role of GSTM1, GSTT1, and GSTP1 polymorphisms in the susceptibility to chemotherapeutic agent toxicity and have shown that individuals carrying GST variant genotypes are less able to detoxify the metabolites of drugs and carcinogens used for treating colorectal cancer, bladder cancer, osteosarcoma, and breast cancer, among others Djukic et al, 2013;Duggan et al, 2013;Vreuls et al, 2013;Kap et al, 2014). Kap et al (2014) conducted a study involving 755 patients with colorectal cancer and found that GSTM1 might be a predictive marker for the success of oxaliplatin therapy.…”

“…Kap et al (2014) conducted a study involving 755 patients with colorectal cancer and found that GSTM1 might be a predictive marker for the success of oxaliplatin therapy. Djukic et al (2013) conducted a study with 105 patients with muscle invasive bladder cancer and reported that the GSTT1 active genotypes might have a prognostic role for treatments. Zhang et al (2012) reported the predictive value of GST gene polymorphisms for the prognosis of osteosarcoma patients receiving chemotherapy; the results showed that the GSTP1 gene polymorphism might have an important role in this cohort.…”

Upregulated glutathione transferase omega-1 correlates with progression of urinary bladder carcinoma

“…Moreover, overexpression of GSTO1-1 is associated with the onset of drug resistance in HeLa cells, as well as in protection against cisplatin-induced apoptosis. Resistance of these tumors to therapy protocols containing cisplatin [7] is a frequent problem in clinical practice. This is probably due to activation of survival pathways (Akt and ERK1/2) and inhibition of apoptotic pathways (JNK1) [8].…”