核苷酸切除修复通路基因tSNPs筛选及其与高发区食管癌易感性

项目名称： 核苷酸切除修复通路基因tSNPs筛选及其与高发区食管癌易感性

项目编号： No.81072360

项目类型： 面上项目

立项/批准年度： 2011

项目学科： 电工技术

项目作者： 代丽萍

作者单位： 郑州大学

项目金额： 10万元

中文摘要： 本研究旨在探讨ERCC2基因多态性与食管癌遗传易感性关系，以及基因-基因、基因-环境之间的交互作用在食管癌发生中的作用。采用病例对照研究方法收集资料，PCR－RFLP检测ERCC2基因3个标签SNP（rs3916874, rs238415, and rs1615836）和2个功能性位点（Asp312Asn 和 Lys751Gln）基因型。结果Lys751Gln位点突变基因型（AC+CC）能降低食管癌发病的风险（OR：0.70，95%CI：0.50-0.95)；单体型GCGGC和单体型GGAGC能增加患病的风险：单体型GCGGC（OR: 2.16, 95% CI: 1.27-3.57）； 单体型GGAGC（OR: 3.72, 95%CI: 1.89-6.63）。MDR软件分析基因与环境交互作用显示rs238415, rs1618536和家族史存在正交互作用（OR: 3.23, 95% CI: 2.37-4.40）。提示ERCC2基因多态性与食管癌易感性有关，且与家族史之间正交互作用。为食管癌的高风险估计、基因治疗和综合防制提供理论依据。

中文关键词： 食管癌；单核苷酸多态性；ERCC2基因；单体型

英文摘要： The incidence rate and mortality rate of esophageal cancer(EC) in China is most high worldwide.Gene polymorphisms and environrment factors are all play important roles during the carcinoma developing process, furthermore, genetic susceptibility determines whether biological and environmrntal factors can cause serious outcomes. The main aim of this study is to explore the relationship of the genetic polymorphisms of ERCC2 and susceptibility to esophageal squamous cell carcinoma ( ESCC) and the role of gene-gene and gene-environment interactions in the development of ESCC. A case-control study was carried out in Henan Province. Behavior hobby (smoking, drinking), individual data were collected. The genotypes of three tag SNPs（rs3916874, rs238415, and rs1615836）and two functional SNPs (Asp312Asn and Lys751Gln) were detected by using the polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLP). We found that genotypes carrying minor allele of Lys751Gln had a decreased risk of esophageal cancer (aOR: 0.70, 95%CI: 0.50-0.95), and two ERCC2 haplotypes were associated with risk of esophageal cancer. Haplotype GCGGC and haplotype GGAGC were strongly associated with an increased risk of esophageal cancer (OR: 2.16, 95% CI: 1.27-3.57 for haplotype GCGGC ; OR: 3.72, 95%CI: 1.89-6.63 for haplotype GGAGC). Gene-environment interaction analysis by MDR software showed that three-factor-model including rs238415, rs1618536 and family history of cancer had higher risk for esophageal cancer in an OR with a P value under 0.0001(OR: 3.23, 95% CI: 2.37-4.40). These results suggested that genetic variations in the ERCC2 gene are associated with risk of esophageal cancer, and there are significantly synergy interaction between gene polymorphisms and family history.

英文关键词： Esophageal cancer ; polymorphism; Haplotype; ERCC2