染色体6q25.1区域多态性与乳腺癌遗传易感性的关系及功能研究

项目名称： 染色体6q25.1区域多态性与乳腺癌遗传易感性的关系及功能研究

项目编号： No.81202275

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： 张丽娜

作者单位： 天津医科大学

项目金额： 23万元

中文摘要： 乳腺癌是复杂的多基因疾病，遗传因素发挥了重要作用。我们参与的乳腺癌GWAS研究发现多态位点SNP rs2046210与亚洲女性乳腺癌的患病风险相关。该位点位于染色体6q25.1区域,雌激素受体α（ESR1）基因上游15kb，未知基因C6orf97的下游。前期工作中发现rs2046210突变基因型与乳腺癌组织中ESR1和C6orf97基因的高表达密切相关，同时这两个基因的表达呈正相关。ERα是乳腺癌内分泌治疗的重要靶点，提示我们此易感区域和未知基因C6orf97非常重要，可能成为潜在的乳腺癌的检测和治疗靶点。本研究着重于将大样本人群作为研究对象对乳腺癌GWAS结果6q25.1区域，进行精细作图，与环境因素的交互作用分析，并对此易感区域SNPs和C6orf97进行功能探索，为阐明乳腺癌的病因及其发生机制，筛选易感人群，开展早期诊断及实施对象明确的个体预防措施提供基础，具有深远的临床意义。

中文关键词： 乳腺癌；单核苷酸多态性；全基因组关联研究；易感性；雌激素受体

英文摘要： Breast cancer is a complex polygenic disorder for which genetic factors play a significant role in disease etiology. We recently identified a novel single nucleotide polymorphism (SNP) rs2046210 for breast cancer risk in a genome-wide association study (GWAS) conducted among Asians. SNP rs2046210 is located at chromsome 6q25.1 region, with 15kb upstream of estrogen receptor α (ESR1) and 6kb downstream of unknown gene C6orf97. We found in previous work that rs2046210 mutant genotype was associated with high expression of gene ESR1 and C6orf97 in breast tumor tissues. These two genes were positively correlated in breast tumor tissues and are associated with estrogen metabolism. ERα is an important target for the endocrine treatment of breast cancer, suggesting this susceptibility region and unknown gene C6orf97 are very important and may become a potential target for breast cancer detection and therapy. This study focus on fine-mapping of the breast cancer susceptibility region 6q25.1 in a large population, and interaction analysis with the environmental factors, and functional exploration for significant SNPs in this region and unknown gene C6orf97. It's facilitate to clarify the breast cancer etiology and pathogenesis, and screening of susceptible populations. More importantly, the significent findings of this s

英文关键词： breast cancer；single nucleotide polymorphism；genome wide association study；susceptibility；estrogen receptor