Genetic polymorphism of glutathione S‐transferase genes (GSTM1, GSTT1 and GSTP1) and susceptibility to prostate cancer in Northern India

Abstract

OBJECTIVE: To examine the association of glutathione-S-transferase (GST) gene polymorphisms in patients with sporadic prostate cancer, in a North Indian population, as GSTs are active in detoxifying a wide variety of endogenous or exogenous carcinogens, and genetic polymorphisms of GSTM1, GSTT1 and GSTP1 have been assessed to evaluate the relative risk of various cancers. PATIENTS AND METHODS: We assessed 127 patients with prostate cancer and 144 age-matched controls, all from North India. The GSTT1 and GSTM1 null genotypes were identified by multiplex polymerase chain reaction (PCR) in peripheral blood DNA samples, and GSTP1-313 A/G polymorphism was determined by PCR/restriction fragment length polymorphism. RESULTS: There was a significant association in null alleles of the GSTM1 (odds ratio 2.239, 95% confidence interval 1.37-3.65, P = 0.001) and GSTT1 (1.891, 1.089-3.282, P = 0.026) with prostate cancer risk, and in the -313 G alleles (Val) of the GSTP1 gene (2.48, 1.51-4.08, P < 0.001). The combined analysis of these three genotypes showed a further increase in the risks of prostate cancer (7.23, 2.42-22.6, P < 0.001). CONCLUSION: The GSTP1-313 G polymorphism, and null alleles of GSTM1 and GSTT1, are strong predisposing risk factors for sporadic prostate cancer in North India.