Genetic polymorphisms of cytochrome P450 2E1, glutathione S-transferase M1 and T1, and susceptibility to gastric carcinoma in Taiwan

Abstract

Background and aims: Cytochrome P450 (CYP) and glutathione S-transferase (GST) enzymes are involved in activation and detoxification of many potential carcinogens. Genetic polymorphisms in these enzymes have been found to influence interindividual and interethnic susceptibility to cancer. Although CYP and GST enzymes are involved in the activation and detoxification of N-nitrosamines and related compound, studies on the relationship between genetic polymorphisms of CYP2E1, GSTT1, and GSTM1 and the risk of gastric carcinoma (GC) are few, and the results have been conflicting. Patients and methods: We conducted a hospital-based case-control study to investigate whether such variations affect the risk of developing GC. Subjects included 356 GC patients and 278 unaffected controls. Peripheral white blood cell DNA was obtained from all subjects. Genotyping of CYP2E1 was performed using a PCR-based restriction fragment length polymorphism assay. Deletion of GSTT1 and GSTM1 genes was assessed by multiplex PCR. Results: The distribution of c2/c2 genotype of CYP2E1, detected by PstI or RsaI digestion, differed significantly between GC patients and controls; the odds ratio was 2.9. It remained significant after adjustment with gender, histological subtypes (diffuse, intestinal, mixed), location (cardia, body, antrum/angle), and stage (early, advanced). In contrast, the prevalence of CYP2E1 DraI polymorphism and GSTT1 and GSTM1 null genotype was similar in controls and GC patients. Conclusion: Our findings suggest that the CYP2E1 genotype is a determinant of GC risk in Taiwan.