Consortium Study to Identify Breast Cancer Susceptibility Loci

确定乳腺癌易感性位点的联合研究

基本信息

批准号：
8520969
负责人：
Jirong Long
金额：
$ 15.6万
依托单位：
VANDERBILT UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-02-15 至 2016-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8520969
关键词：
ABCC1 gene Accounting African American Architecture Asia Asian Americans Asians BRCA1 gene BRCA2 gene Breast Cancer Genetics Breast Cancer Prevention Cancer Biology Chinese People Complex DNA Data Disease Epidemiologic Studies Ethnic group Etiology European Evaluation Frequencies Funding Future Genes Genetic Genetic Markers Genetic Predisposition to Disease Genetic Risk Genetic Variation Genomics Goals High Risk Woman Human Genome Japanese Population Koreans Life Malignant Neoplasms Maps Methodology Modeling Parents Pathway interactions Penetrance Persons Phase Play Population Predisposition Primary Prevention Recruitment Activity Reporting Research Design Risk Risk Assessment Role Sampling Scanning Secondary Prevention Staging Susceptibility Gene Technology United States Variant Woman Women&apos s Health base cancer genetics cancer genome cancer risk case control cost genetic association genetic variant genome wide association study improved malignant breast neoplasm new technology next generation novel public health relevance

项目摘要

DESCRIPTION (provided by applicant): Breast cancer is the most common malignancy among women in the United States and many other parts of the world. Genetic factors play an important role in the etiology of breast cancer. Recent genome-wide association studies (GWAS) have identified multiple genetic susceptibility loci for breast cancer. However, these newly- identified genetic factors, along with high-penetrance susceptibility genes reported previously (such as the BRCA1 and BRCA2 genes), explain only a small fraction of genetic variation for breast cancer. In this application, we propose two novel projects that will significantly advance our understanding of the genetic basis for breast cancer and the methodology used for genetic epidemiologic research. The first project is a GWAS based on the newly-established Asia Breast Cancer Consortium and will include over 27,000 cases and controls recruited from 11 studies conducted among Asian women living in various parts of the world. Through analyzing GWA scan data from 3,500 cases and 3,500 controls, we will identify and evaluate the top 8,500 SNPs in an independent set of 3,500 cases and 3,500 controls and then validate approximately the top 100 SNPs in 6,700 cases and 6,700 controls. In the second project, we will sequence eight GWAS-mapped regions in 3,000 cases and 3,000 controls with the goal of identifying additional genetic risk variants, particularly low- frequency variants, for breast cancer in these regions. We will select up to 180 promising SNPs for replication in an independent set of 2,500 cases and 2,500 controls and then select the top 30 SNPs for further evaluation in another independent set of 2,500 cases and 2,500 controls. This is the only well-powered GWAS conducted in Asian women, and thus is the only existing GWAS capable of discovering genetic variants for breast cancer that are unlikely or more difficult to identify in other GWAS. The proposed sequencing project represents a new model for future genetic association studies. These two newly-proposed projects will be built upon several well- conducted, NCI-funded studies to generate substantial novel information that will help to not only understand breast cancer biology and genetics, but also to improve risk assessment models and identify high-risk women for cost-efficient prevention of breast cancer. PUBLIC HEALTH RELEVANCE: Genetic factors play a major role in the etiology of breast cancers, yet only a small number of cases are explained by genetic factors identified thus far. The large epidemiologic study we propose will comprehensively evaluate genetic markers in relation to breast cancer risk. This study will generate valuable results for the identification of high-risk women for the primary and secondary prevention of breast cancer.

描述（由申请人提供）：乳腺癌是美国和世界许多其他地区女性最常见的恶性肿瘤。遗传因素在乳腺癌的病因学中起着重要作用。最近的全基因组关联研究（GWAS）已经确定了乳腺癌的多个遗传易感位点。然而，这些新发现的遗传因素，以及之前报道的高外显率易感基因（例如 BRCA1 和 BRCA2 基因），只能解释乳腺癌遗传变异的一小部分。在本申请中，我们提出了两个新项目，将显着增进我们对乳腺癌遗传基础和遗传流行病学研究方法的理解。第一个项目是基于新成立的亚洲乳腺癌联盟的 GWAS，将包括从生活在世界各地的亚洲女性中进行的 11 项研究中招募的 27,000 多个病例和对照。通过分析 3,500 个病例和 3,500 个对照的 GWA 扫描数据，我们将识别和评估一组独立的 3,500 个病例和 3,500 个对照中的前 8,500 个 SNP，然后验证 6,700 个病例和 6,700 个对照中的大约前 100 个 SNP。在第二个项目中，我们将对 3,000 个病例和 3,000 个对照中的 8 个 GWAS 映射区域进行测序，目的是识别这些区域中乳腺癌的其他遗传风险变异，特别是低频变异。我们将选择最多 180 个有前途的 SNP 在一组独立的 2,500 个病例和 2,500 个对照中进行复制，然后选择前 30 个 SNP 在另一组独立的 2,500 个病例和 2,500 个对照中进行进一步评估。这是在亚洲女性中进行的唯一一个功能强大的 GWAS，因此也是现有的唯一一个能够发现乳腺癌遗传变异的 GWAS，而这些变异在其他 GWAS 中不太可能或更难以识别。拟议的测序项目代表了未来遗传关联研究的新模型。这两个新提出的项目将建立在多项实施良好、NCI 资助的研究的基础上，以产生大量新颖的信息，不仅有助于了解乳腺癌生物学和遗传学，而且有助于改进风险评估模型并识别高风险女性以具有成本效益的方式预防乳腺癌。公共卫生相关性：遗传因素在乳腺癌病因学中发挥着重要作用，但迄今为止仅发现了少数病例可以用遗传因素来解释。我们提议的大型流行病学研究将全面评估与乳腺癌风险相关的遗传标记。这项研究将为识别高危女性进行乳腺癌的一级和二级预防产生有价值的结果。