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Molecular mechanisms of individual susceptibility to esophageal cancer remain unknown although genetic polymorphisms of xenobiotic-metabolizing enzymes were shown to be associated with risks of many types of human cancers. To develop and validate molecular biomarkers for carcinogen exposure studies, a case-control study was conducted in recently diagnosed 107 esophageal cancer cases and 107 residency, age, and sex-matched controls in Huaian, China, an endemic area of esophageal cancer with annual incidence of over 80/100,000. In addition to the regular epidemiological analysis, genetic polymorphisms of cytochrome P450 2E1 (CYP2E1), glutathione S-transferase M1 (GSTM1) and GSTT1, and microsomal epoxide hydrolase (EPHX) were assessed from genomic DNA samples of all subjects. CYP2E1 and EPHX genotypes were analyzed by PCR amplification followed by restriction fragment length polymorphism (RFLP). Genotypes of GSTM1 and GSTT1 were detected by a multiplex PCR method. Conditional Logistic regression analysis for epidemiological and food frequency questionnaires found that eating fast, more salted and acrid food consumption, and pickled vegetable and former mildewed food intake were significant risk factors (P < 0.01-0.001). No statistically significant difference was found in frequency of CYP2E1 c1/c1 alleles between cases (62.3%) and controls (63.8%). A slightly increased risk with odds ratio (OR) of 1.3 and 95% confidence interval (CI) of 0.6-3.2 was found in female cases with the c1/c2 genotype. Neither the GSTM1/GSTT1 null/null (-/-) nor GSTM1 null genotypes were significant different between cases and controls; however, the frequency of GSTT1 null genotype appeared to be higher in cases (59.4%) compared to the controls (47.2%) with OR of 1.6 and 95% CI of 1.0-2.8 (P = 0.074), and was more frequently in male cases (64.4%) compared to the controls (41.4%) with OR of 2.6 and 95% CI of 1.2 - 5.4 (P=0.013). These results suggest that the genetic polymorphism of GSTT1, along with environmental carcinogen exposure, may play important roles in the development of esophageal cancer in this high-risk area. (Supported by the NIH research grant CA94683).

[Proc Amer Assoc Cancer Res, Volume 46, 2005]