Genotypes of GSTM1 and GSTT1: Useful determinants for clinical outcome of bladder cancer in Pakistani population

Abstract

Background: Incidence of bladder cancer has increased rapidly worldwide in the past few years. Environmental as well as genetic factors are involved in the etiology of bladder cancer. Glutathione S transferase mu 1 (GSTM1) and glutathione S transferase theta 1 (GSTT1) genes are two xenobiotic metabolizing genes in phase II of detoxification process.

Aim: The current study was aimed to find out the association of different environmental factors and GSTM1 and GSTT1 gene polymorphisms with susceptibility to bladder cancer in Pakistani population.

Method: Bladder cancer cases (236) and control blood samples (270) were screened using phenol chloroform method of DNA extraction followed by multiplex PCR.

Results: With respect to age; bladder cancer was more prevalent in age >60 years and low grade tumors were more frequent than high grade tumors. Smokers had a significantly higher incidence rate of cancer; also family history of cancer was found to be strongly associated (P < 0.05) with bladder cancer. Commonly reported symptoms by the patients of bladder cancer were hematuria, lower urinary tract symptoms (LUTS) and flank pain. A larger number of patients had undergone surgery, chemotherapy and radiotherapy. Similarly GSTM1 (OR 2.24; CI 1.5–3.2; P = 0.0001) and GSTT1 (OR 2.9; CI 1.4–6.1; P = 0.002) gene deletion showed a highly significant association with bladder cancer. Simultaneous deletions of both GSTM1 and GSTT1 genes also showed highly significant association (OR 5.3; CI 2.1–13.1; P =0.0001) with cancer risk. No association was found when both of the two genes deletion was compared with bladder cancer among smokers.

Conclusion: This study suggests that GSTM1 and GSTT1 gene polymorphisms may be associated with increased susceptibility toward bladder cancer in Pakistani population.

Keywords: GSTM1; GSTT1; Bladder cancer; PCR; Polymorphism