Polymorphism of CYP1A1and mEH Genes and Susceptibility to Bladder Cancer in Northern India
Purpose: Most environmental pro-carcinogens require metabolic activation by phase I enzymes (CYP450s) whereas microsomal epoxide hydrolase (mEH) are mainly active in the detoxification of wide variety of endogenous or exogenous carcinogens. The genetic polymorphisms of CYP1A1 and mEH genes have been studied earlier to evaluate the relative risk of various cancers. In the present study, we examined the association of the CYP1A1 and mEH gene polymorphisms with sporadic bladder cancer patients (CaB) in Northern India.
Methods: We studied 106 incidents of CaB cases and 160 age matched controls from North India. The CYP1A1and mEH genotypes were determined by PCR/RFLP (polymerase chain reaction/restriction fragment length polymorphism) method from DNA extracted from peripheral blood of the patients and controls. Binary Logistic Regression Model (BLMR) was used for assessing differences in genotype prevalence and their association between patients and the control group.
Results: We observed non-significant association in T/C polymorphism of the CYP1A1 gene; however, the exon-3 His genotype of the mEH gene polymorphism alone (OR = 2.67, P=0.001) /or in combination with tobacco-users were significant for risk of bladder cancer. However no association was observed with stage or grade of bladder tumor with these genotypes. Upon stratification of age in bladder cancer patients, association between exon-3 of mEH genotypes and the age group 46-55 demonstrated a significant risk of bladder cancer.
Conclusion: Our study suggests that exon-3 His genotype of the mEH gene polymorphism is a risk factor for sporadic bladder cancer specifically in 46-55 age group and more so in case of tobacco users in North India.