Genetic Factors for Breast Cancer- A genome Wide Study

描述（由申请人提供）：乳腺癌是世界上许多地区妇女中最常见的恶性肿瘤。遗传因素在乳腺癌的病因学中起重要作用。然而，到目前为止，只有少数乳腺癌易感基因被确定，它们只能解释普通人群中很小一部分乳腺癌病例。在过去的10年里，人们进行了大量的候选基因研究。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显著进步，开展全基因组关联（GWA）研究系统评估乳腺癌遗传危险因素已成为可能。本申请中提出的多阶段GWA研究将建立在由NCI资助的两项正在进行的大型研究的资源基础上，上海乳腺癌研究（R01 CA64277）是一项基于人群的病例对照研究，上海妇女健康研究（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8000例乳腺癌病例和对照组。在研究的第一阶段，我们将使用Illumina HumanHap550 BeadChip对1000例患者和1000例对照组进行GWA扫描。然后，我们将在1500例病例和1500例对照的独立样本中选择10600个最有希望的snp进行验证研究。所有有希望的snp将使用从前瞻性上海妇女健康研究中选择的1000例病例和2000例对照的数据进一步验证。这项新提出的研究的母项目以强有力的方法进行得非常好。我们的初步研究已清楚地证明了建议研究的可行性和实用性。这项研究是独一无二的，有许多独特的特点，有助于对乳腺癌遗传因素进行严格的评估。这项研究的结果将对确定高危妇女进行乳腺癌的一级和二级预防有价值。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，只有少数病例可以用遗传因素来解释。我们提出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。本研究将为确定高危妇女乳腺癌的一级和二级预防提供有价值的结果。

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.