GENETIC-POLYMORPHISM OF GSTM1, CYP2E1 AND CYP2D6 IN EGYPTIAN BLADDER-CANCER PATIENTS

Polymorphic changes in the GSTM1, CYP2E1 and the CYP2D6 genes have bee n reported to be individually associated with increased susceptibility to certain cancers, In the present study, the relationship between ge netic polymorphism for these genes and development of urinary bladder cancer among Egyptian patients was investigated, Our results indicate that the frequency of bladder cancer patients with the GSTM1 null geno type is significantly higher than that of the normal controls (86.3 an d 47.6%, respectively) with an odds ratio (OR) of 6.97 (95% CL = 1.59- 30.57, Fisher's exact P = 0.008), In contrast, our investigation faile d to demonstrate any difference in the distribution of CYP2E1 polymorp hism between bladder cancer patients and controls as detected by PstI restriction fragment length polymorphism (RFLP) analysis. RFLP analysi s of the CYP2D6 gene revealed a non-significant increase in the number of extensive metabolizers (EM) among the patients compared to the con trols (68 versus 48%). However, the EM genotypes enhances the risk fur ther for individuals harboring the GSTM1 null genotype as individuals harboring both the EM and the GSTM1 null genotypes have an odds ratio of 14.0 (95% CL = 1.3-151.4, Fisher's exact P = 0.02) compared to indi viduals harboring the EM and the GSTM1+/+ genotypes. In conclusion, ou r results indicate that genetic polymorphism, especially in GSTM1 and CYP2D6 could play an important role as host risk factors for developme nt of urinary bladder cancer among Egyptians.