细胞色素P450 2E1和谷胱甘肽转硫酶P1基因与食管癌易患性

目的研究与致癌物亚硝胺代谢激活有关的细胞色素Ｐ４５０２Ｅ１基因（ＣＹＰ２Ｅ１）,和与致癌物代谢解毒有关的谷胱甘肽转硫酶Ｐ１基因（ＧＳＴＰ１）多型性与食管癌易患性的关系。方法采用病例－对照分子流行病学方法。以ＰＣＲ－ＲＦＬＰ方法分析食管癌、食管上皮重度增生病例,和与其年龄性别配对的正常对照者（各４５例）ＣＹＰ２Ｅ１和ＧＳＴＰ１的基因型。结果ＧＳＴＰ１基因型在病例和对照者中的分布无显著差别,但ＲｓａＩ识别的ＣＹＰ２Ｅ１基因型,在食管癌、食管上皮重度增生病例及其正常对照者中的分布差别显著。ＣＹＰ２Ｅ１突变型基因频率在正常对照组中为５５．６％,显著高于食管上皮重度增生病例（１７．８％）和食管癌病例（２０．０％;χ２＝２０．８,Ｐ＜０．００１）;携带野生型ＣＹＰ２Ｅ１的个体,发生食管上皮重度增生和食管癌的危险性,比携带变异型ＣＹＰ２Ｅ１的个体各高５倍。结论ＣＹＰ２Ｅ１基因是涉及食管癌变早期过程的遗传易患性因素。

Genetic polymorphisms of cytochrome P450 2E1 and glutathione S-transferase P1 and susceptibility to esophageal cancer

OBJECTIVES: To study the association between genetic polymorphisms of cytochrome P4502E1 (CYP2E1) and/or glutathione S-transferase P1 (GSTP1) and susceptibility to esophageal cancer. METHODS: Genotyping of CYP2E1 and GSTP1 was performed using PCR-based RFLP analysis on DNA isolated from surgically removed esophageal tissues or scraped esophageal epithelium from cancer cases (n = 45), severe epithelial hyperplasia cases (n = 45), and normal controls (n = 45). RESULTS: The variant genotypes (c1/c2 and c2/c2) detected by RsaI digestion was found in 17% of epithelial hyperplasia cases, 20.0% of esophageal cancer cases and 55.6% of controls, with the differences being statistically significant (P < 0.001). Subjects carrying wild-type genotype of CYP2E1 had more than 5-fold risk for developing severe epithelial hyperplasia (odds ratio, OR = 5.78; 95% confidence interval, CI = 2.2-15.2) and esophageal cancer (OR = 5.00; 95% CI = 2.0-12.8). No association with the risk of severe epithelial hyperplasia and esophageal cancer was observed for the DraI polymorphism of CYP2E1 or for the Awl26I polymorphism of GSTP1. CONCLUSION: CYP2E1 is a genetic susceptibility factor involved in the early events for esophageal carcinogenesis.