食管癌转移高风险性相关的SNP位点筛查研究

项目名称： 食管癌转移高风险性相关的SNP位点筛查研究

项目编号： No.30872549

项目类型： 面上项目

立项/批准年度： 2009

项目学科： 金属学与金属工艺

项目作者： 杨康

作者单位： 中国人民解放军第三军医大学

项目金额： 31万元

中文摘要： 肿瘤转移是食管癌术后的主要死因，而转移的风险性与个体的基因多态性有关。本项目在已建立的食管癌病例标本和病例资料数据库的基础上，选取MMPs、survivin、COL4A2、 PIWIL1、 COL4A2、KRAS 、Bax、DCR3、pre-miR-146a 、pre-miR-196a, SERPINB等21个肿瘤转移相关基因，直接筛选得到位于启动子区、编码区以及3'UTR区等功能区的56个SNP位点，采用病例对照设计方案，用SNPshot等SNP检测方法，完成了其中32个SNP位点的基因分型及关联分析。结果发现，位于Survivin基因启动子区的SNP位点-625G/C以及位于DcR3基因启动子区的147 C/T位点与食管癌发病风险显著相关，位于MMP-9基因编码区的R279Q位点以及serpin基因家族的多个编码区非同义SNP位点显著增加了人群患ESCC的发病风险，位于pre-miR-146a和196a2功能区的两个多态性位点与食管癌发生和转移均显著相关。本研究的结果为食管癌转移风险的评估研究提供了实验基础。

中文关键词： 食管癌；易感性；转移；单核苷酸多态性

英文摘要： Metastasis is the main cause of death after esophageal cancer surgery. The risk of metastasis is associated with genetic polymorphism. We established a sample bank and a case/follow-up database of esophageal cancer. Based on the candidate-gene approach, we selected 21 tumor metastasis associated genes such as MMPs、survivin、COL4A2、 PIWIL1、 COL4A2、KRAS 、Bax、DCR3、pre-miR-146a 、pre-miR-196a, SERPINB et.al, and screened 56 functional SNPs located in the promoter/coding/3'UTR regions.In the case-control design,32 SNPs were genotyped by SNPshot on ABI 3130 genetical analysis platform in Chinese han population. Association analysis showed that SNP -625G/C in the promoter of Survivin and rs2257440 (147 C/T) in the DcR3, R279Q in the coding region of MMP9 and a 5 SNPs in the coding region of serpin family gene, 2 SNPs in the functional regions of pre-miR-146a (rs2910164) and pre-miR-196a2 (rs11614913) were associated with risk and metastasis of esophageal cancer. We also performed meta analysis on association between polymorphisms in the promoter regions of matrix metalloproteinases 1/3 and cancer susceptibility and metastasis. The results of this project will promote the development and application of the diagnosis technology of tumor meatstasis, contribute to the development of individualized treatment and provide new ways to enhance the early diagnosis and long-term survival of esophageal cancer patients.

英文关键词： esophageal cancer; susceptibility; metastasis; single nucleotide polymorphism