Genetic polymorphism of drug metabolizing enzymes (CYP2E1, GSTP1) and susceptibility to bladder cancer in North India.

Glutathione-S-transferases (GSTs) are active in the detoxification of wide variety of endogenous or exogenous carcinogens and genetic polymorphisms of CYP2E1 and GSTP1 genes have been studied extensively to evaluate the relative risk of various cancers. In the present study, we examined associations with CYP2E1 and GSTP1 gene polymorphisms in sporadic bladder cancers from North Indian patients. The subjects were 106 bladder cancer (Ca-B) cases and 162 age-matched controls. The GSTP1 313 A/G polymorphism was determined by the PCR/RFLP method using peripheral blood DNA. Binary Logistic Regression Model was used for assessing differences in genotype prevalence and their associations between patient and the control group. We observed a non-significant association in Pst1 polymorphism of the CYP2E1 gene; though the A/G genotype (OR = 2.69, 95% CI=1.57- 4.59, P= 0.000) and G/G genotype (OR = 7.68, 95% CI=2.77- 21.26, P= 0.000) of the GSTP1 gene polymorphism alone or in combination with tobacco users were highly significant (OR=24.06; 95% CI: 4.80- 120.42; P =0.000) when compared to the controls. The results of our study demonstrated that the GSTP1 313 G/G polymorphism is a strong predisposing risk factor for bladder cancer in the North Indian population.

Allelic variation of GSTT1, GSTM1 and GSTP1 genes in North Indian population.

Glutathione S-transferase (GST) enzymes are involved in detoxification of many potentially carcinogenic compounds. Homozygous deletions or null genotypes of GSTT1 and GSTM1 genes and an A to G substitution at nucleotide 313 in GSTP1 have been reported in different populations. Intra-ethnic as well as interethnic differences are known to exist in the frequencies of the above GST genes. The present study was therefore undertaken to determine the prevalence of GSTM1 and GSTT1null alleles, as well as the GSTP1 gene polymorphism, in 370 healthy individuals in a North Indian population. Genotyping of M1 and T1 was performed using a multiplex polymerase chain reaction and the GSTP1 polymorphism was determined by the polymerase chain reaction/restriction fragment length polymorphism (PCR-RFLP) method. The frequencies of GSTM1 and GSTT1 null alleles in normal healthy individuals were observed to be 33.0% and 18.4% respectively. In 7.0% of individuals' concomitant lack of M1 and T1 genes were observed. For GSTP1, wild (Ile/Ile), heterozygous (Ile/Val) and mutant (Val/Val) genotypes were observed for 44.3%, 50.3% and 5.4% of individuals respectively. The prevalence of the M1 null allele is significantly lower than those documented for English, Turkish, Chinese, Caucasians, Japanese and white (Brazilian and American) populations. However, a significantly higher frequency for T1 null was reported in Chinese and Japanese population. Furthermore, Japanese and African American populations have exhibited significantly higher frequencies of wild and mutant P1 genotypes, respectively, than the Indian population. Thus, our results signify an impact of ethnicity and provide a basis for future epidemiological and clinical studies.