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

BackgroundIncidence 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.AimThe 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.MethodBladder cancer cases (236) and control blood samples (270) were screened using phenol chloroform method of DNA extraction followed by multiplex PCR.ResultsWith 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.ConclusionThis study suggests that GSTM1 and GSTT1 gene polymorphisms may be associated with increased susceptibility toward bladder cancer in Pakistani population.