HRR通路miRNA及其靶序列SNP与乳腺癌遗传易感性关联分析及功能论证

项目名称： HRR通路miRNA及其靶序列SNP与乳腺癌遗传易感性关联分析及功能论证

项目编号： No.81202278

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 预防医学、地方病学、职业病学、放射医学

项目作者： 宋春花

作者单位： 郑州大学

项目金额： 23万元

中文摘要： 乳腺癌是危害女性健康的最常见恶性肿瘤之一，micro-RNA通过调控多种肿瘤相关基因参与乳腺癌发生发展。研究表明micro-RNA靶序列SNP是肿瘤一个重要的遗传标记体系，同时近年来多项GWAS结果提示HRR通路基因SNP与乳腺癌的遗传易感性相关；但现有HRR通路基因靶序列SNP与乳腺癌的关联研究规模较小且缺乏后续功能论证，不足以阐述此类SNP在乳腺癌病因中的作用。本研究利用生物信息学选取符合一定频率标准全部HRR相关micro-RNA种子区靶序列SNPs，通过大样本病例对照研究，从单位点、多位点联合作用、microRNA-SNP位点互作分析，并在此基础上通过荧光素酶报告系统、实时定量PCR、免疫组化等技术，探讨HRR相关micrioRNA及其靶序列结合位点SNP对乳腺癌发生的调控作用，为乳腺癌的高发风险估计、个体化预防、干预及治疗提供理论依据。

中文关键词： 乳腺癌；遗传易感性；同源重组修复；miRNA；单核苷酸多态性

英文摘要： Breast cancer has become one of the primary malignant tumor of endangering women's health, micro-RNA involved in breast cancer development by regulating a variety of tumor-related genes. Researches indicated micro-RNA target sequences' SNP is an important genetic marker system of tumor, and in recent years a number of GWAS results prompted HRR pathway genes' SNP was related with genetic susceptibility of breast cancer; However, the existing researches about HRR SNP genetic target sequences associated with breast cancer were relatively small and lack of follow-up functional feasibility studies, so they're insufficient to explain this type of SNP's role in the etiology of breast cancer. This research conforms to certain frequency standard HRR micro-RNA seed area target sequences' SNPs by Bio-informatics, through case-control study of large sample, the combined effect of point, multiple points and microRNA-SNP points interaction analysis, on this bases, the regulation and control role of HRR related micrioRNA and its target sequence SNP to breast cancer were explored in by the technologies such as the luciferase reporter system, real-time quantitative PCR, immunohistochemistry, it'll provide a theoretical basis for the high risk assessment, individualization prevention, intervention and treatment of breast cancer.

英文关键词： breast cancer；genetic susceptibility；HRR；miRNA；SNP