SUSCEPTIBILITY TO ESOPHAGEAL CANCER AND GENETIC POLYMORPHISMS IN GLUTATHIONE S-TRANSFERASES T1, P1, AND M1 AND CYTOCHROME-P450 2E1

Genetic polymorphisms in enzymes involved in carcinogen metabolism hav e been shown to influence susceptibility to canter. Cytochrome P450 2E 1 (CYP2E1) is primarily responsible for the bioactivation of many low molecular weight carcinogens, including certain nitrosamines, whereas glutathione S-transferases (GSTs) are involved in detoxifying many oth er carcinogenic electrophiles, Esophageal cancer, which is prevalent i n China, is hypothesized to be related to environmental nitrosamine ex posure. Thus, we conducted a pilot case-control study to examine the a ssociation between CYP2E1, GSTM1, GSTT1, and GSTP1 genetic polymorphis ms and esophageal cancer susceptibility. DNA samples were isolated fro m surgically removed esophageal tissues or scraped esophageal epitheli um from cases with cancer (n = 45), cases with severe epithelial hyper plasia (n = 45), and normal controls (n = 46) from a high-risk area, L inxian County, China. RFLPs in the CYP2E1 and the GSTP1 genes were det ermined by PCR amplification followed by digestion with RsaI or DraI a nd Alw26I, respectively, Deletion of the GSTM1 and GSTT1 genes was exa mined by a multiplex PCR, The CYP2E1 polymorphism detected by RsaI was significantly different between controls (56%) and cases with cancer (20%) or severe epithelial hyperplasia (17%; P < 0.001), Persons witho ut the RsaI variant alleles had more than a 4-6-fold risk of developin g severe epithelial hyperplasia (adjusted odds ratio, 6.0; 95% confide nce interval, 2.3-16.0) and cancer (adjusted odds ratio, 4.8; 95% conf idence interval, 1.8-12.4). Polymorphisms in the GSTs were not associa ted with increased esophageal cancer risk. These results indicate that CYP2E1 may be a genetic susceptibility factor involved in the early e vents leading to the development of esophageal cancer.