Genetic Factors for Breast Cancer- A genome Wide Study

乳腺癌的遗传因素——全基因组研究

• 批准号: 8076924
• 负责人: Wei Zheng
• 金额: $ 59.41万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-07-15 至 2013-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8076924
• 关键词: Address; Admixture; Adult; Asians; Biological; Breast Cancer Genetics; Cancer Etiology; Cancer-Predisposing Gene; Candidate Disease Gene; Case-Control Studies; Caucasians; Caucasoid Race; Chinese People; Clinical Data; Cohort Studies; Communities; Data; Environmental Risk Factor; Epidemiologic Studies; Etiology; Evaluation; Exposure to; Funding; Future; General Population; Genetic; Genetic Markers; Health; High Risk Woman; Interview; Investigation; Malignant Neoplasms; Methodology; Nested Case-Control Study; Persons; Phase; Pilot Projects; Play; Population; Primary Prevention; Recruitment Activity; Resources; Risk Factors; Role; Sampling; Secondary Prevention; Surveys; United States; Validation; Woman; Women' s Health; base; cancer risk; case control; cost; gene environment interaction; genetic risk factor; genome wide association study; genome-wide; genotyping technology; malignant breast neoplasm; non-genetic; novel; parent project; population based; prospective; response; sample collection; validation studies

DESCRIPTION (provided by applicant): Breast cancer is the most common malignancy among women in many parts of the world. Genetic factors play an important role in the etiology of breast cancer. However, to date, only a few breast cancer susceptibility genes have been identified, and they explain only a very small fraction of breast cancer cases in the general population. A large number of candidate-gene studies have been conducted over the past 10 years. These studies, however, are clearly inadequate to fully uncover the genetic basis of breast cancer. With recent significant advances in high-throughput genotyping technologies, it has become feasible to conduct genome-wide association (GWA) studies to systematically evaluate genetic risk factors for breast cancer. The multi-phase GWA study proposed in this application will be built upon the resources established in two large, on-going studies funded by NCI, the Shanghai Breast Cancer Study (R01 CA64277) a population-based case-control study, and the Shanghai Women's Health Study (RO1 CA70867) a population-based prospective cohort study. Approximately 8,000 breast cancer cases and controls will be included in this proposed study. In the first phase of the study, we will conduct a GWA scan in 1,000 cases and 1,000 controls using the Illumina HumanHap550 BeadChip. We will then select the 10,600 most promising SNPs for a validation study in an independent sample of 1500 cases and 1500 controls. All promising SNPs will be further validated using data from 1000 cases and 2000 controls selected from the prospective Shanghai Women's Health Study. The parent projects of this newly-proposed study have been exceptionally well-conducted with a strong methodology. The feasibility and utility of the proposed study have been clearly demonstrated in our pilot study. The study is unique and has many unique features that facilitate a rigorous evaluation of breast cancer genetic factors. The results from the study will be valuable in identifying high risk women for primary and secondary prevention of breast cancer. PUBLIC HEALTH RELEVANCE: Genetic factors and gene-environment interaction are believed to cause most 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）：乳腺癌是世界许多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。然而，迄今为止，仅发现了少数乳腺癌易感基因，并且它们只能解释一般人群中极小部分乳腺癌病例。过去10年进行了大量候选基因研究。然而，这些研究显然不足以完全揭示乳腺癌的遗传基础。随着近年来高通量基因分型技术的重大进展，进行全基因组关联（GWA）研究以系统评估乳腺癌的遗传风险因素已变得可行。本申请中提出的多阶段 GWA 研究将建立在 NCI 资助的两项大型、正在进行的研究中所建立的资源之上，上海乳腺癌研究 (R01 CA64277) 是一项基于人群的病例对照研究，而上海乳腺癌研究 (R01 CA64277) 是一项基于人群的病例对照研究。妇女健康研究 (RO1 CA70867) 是一项基于人群的前瞻性队列研究。这项拟议的研究将包括大约 8,000 例乳腺癌病例和对照。在研究的第一阶段，我们将使用 Illumina HumanHap550 BeadChip 对 1,000 个病例和 1,000 个对照进行 GWA 扫描。然后，我们将在 1500 个病例和 1500 个对照的独立样本中选择 10,600 个最有希望的 SNP 进行验证研究。所有有前景的 SNP 将使用从前瞻性上海女性健康研究中选出的 1000 个病例和 2000 个对照的数据得到进一步验证。这项新提出的研究的母项目以强有力的方法论进行得非常好。我们的试点研究清楚地证明了拟议研究的可行性和实用性。该研究是独一无二的，具有许多独特的特征，有助于对乳腺癌遗传因素进行严格评估。该研究的结果对于识别高危女性进行乳腺癌的一级和二级预防非常有价值。公共卫生相关性：遗传因素和基因-环境相互作用被认为是导致大多数乳腺癌的原因，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。