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: 7848916
• 负责人: Wei Zheng
• 金额: $ 63.08万
• 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/7848916
• 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; Complement component C1s; Data; Environmental Risk Factor; Epidemiologic Studies; Etiology; Evaluation; Exposure to; Funding; Future; General Population; Genetic; Genetic Markers; High Risk Woman; Interview; Investigation; Malignant Neoplasms; Methodology; Nested Case-Control Study; Persons; Phase; Pilot Projects; Play; Population; 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; public health relevance; 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中最常见的恶性肿瘤。遗传因素在乳腺癌的病因中起重要作用。但是，迄今为止，仅鉴定出少数乳腺癌的易感性基因，它们仅解释了一般人群中乳腺癌病例的一小部分。在过去的10年中，已经进行了大量候选基因研究。但是，这些研究显然不足以完全揭示乳腺癌的遗传基础。随着高通量基因分型技术的最新进展，进行全基因组关联（GWA）研究以系统地评估乳腺癌的遗传危险因素已变得可行。该应用程序中提出的多相GWA研究将建立在由NCI资助的两项大型，正在进行的研究中建立的资源，上海乳腺癌研究（R01 CA64277）一项基于人群的病例对照研究，上海妇女健康研究（RO1 CA70867）一项基于人群的前瞻性研究。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进行1,000例CAN和1,000例对照进行GWA扫描。然后，我们将在1500例和1500个对照的独立样本中选择10,600个最有前途的SNP进行验证研究。所有有前途的SNP将通过1000例案例和2000个从上海妇女健康研究中选择的2000个对照组进行进一步验证。这项新提出的研究的父项目与强有力的方法相当良好。我们的试点研究清楚地证明了拟议研究的可行性和效用。该研究是独特的，并且具有许多独特的特征，可促进对乳腺癌遗传因素进行严格评估。这项研究的结果对于确定乳腺癌的原发性和继发性预防高风险女性将很有价值。公共卫生相关性：遗传因素和基因环境相互作用被认为会导致大多数乳腺癌，但迄今为止仅通过遗传因素来解释了少数病例。我们提出的大型流行病学研究将全面评估与乳腺癌风险有关的遗传标记。这项研究将为鉴定高风险女性的初级和二级预防乳腺癌而产生宝贵的结果。