The Meningioma Consortium: Genome-Wide Association Study

脑膜瘤联盟：全基因组关联研究

• 批准号: 8547782
• 负责人: Elizabeth B. Claus
• 金额: $ 59.8万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-01 至 2017-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8547782
• 关键词: ATM gene; ATM wt Allele; Accounting; Address; Adult; Age; Amendment; Area; Attention; BRCA1 gene; Benign; Biological; Brain Neoplasms; CCND1 gene; California; Cancer-Predisposing Gene; Case-Control Studies; Caucasians; Caucasoid Race; Cephalic; Clinical; Collection; Connecticut; County; DNA Repair Gene; Data; Data Collection; Diagnosis; Doctor of Philosophy; ERCC2 gene; Epidemiologic Studies; Ethnic Origin; Female; Funding; Genetic; Genetic Markers; Genotype; Geography; Hormones; Housing; Inherited; Interview; Ionizing radiation; KRAS2 gene; Link; Malignant Neoplasms; Massachusetts; Melissa; Neurologic; North Carolina; Pathologic; Patients; Phase; Predisposition; Prevention; Primary Brain Neoplasms; Process; Proteins; Quality of life; Radiation; Relative (related person); Request for Applications; Resources; Risk; Risk Factors; San Francisco; Series; Site; Specimen; Staging; Statutes and Laws; Study Subject; Targeted Research; Texas; Time; United States; United States National Institutes of Health; University Hospitals; Variant; Woman; abstracting; ataxia telangiectasia mutated protein; benign brain tumor cancer registries; cancer genetics; case control; genetic analysis; genome wide association study; male; malignant breast neoplasm; meningioma; population based; sex; tumor

Project Summary/ Abstract Meningioma is the most common primary brain tumor, present in up to one percent of adults, and although often considered benign, has survival comparable to breast cancer. Information on risk factors is extremely limited. In an effort to better define such factors, we are conducting a comprehensive population-based, case/control study of meningioma that includes 1600 cases and 1600 controls drawn from Massachusetts, Connecticut, North Carolina, California and Texas. This will represent the largest population-based collection of meningioma cases worldwide, with more than double the number of cases of any existing study. We are currently collecting biological specimens, and extensive exposure and phenotypic data with funding from the National Institutes of Health (NIH R01s CA109468, CA109461, CA109745, CA108473, and CA109475). In this application we request funds to genotype the study subjects to find inherited risk loci for meningioma. Our aims are to 1) Conduct the first genome wide association study (GWAS) of meningioma using the 1360 Caucasian cases from our ongoing case/control project and 3420 Caucasian controls drawn from the first half of three control series a) 600 controls from our ongoing case/control project, b) 1699 controls from Illumina iControlDB and c) 1121 controls from the Cancer Genetic Markers of Susceptibility (CGEMs) study, 2) Using 700 additional Caucasian meningioma subjects drawn from our clinical series and the second half of the above mentioned controls (n=3420), replicate candidates from Aim 1 that yielded p<10-5 for association with meningioma. Variants with p < 5.0*10-8 will be considered significant for genome wide association with meningioma risk from combined stage 1 and stage 2 analyses, 3) Replicate previous associations from the Interphone study8a of meningioma risk with variants in BRIP1 (the breast cancer susceptibility gene (BRCA1)-interacting protein) and ATM (ataxia telangiectasia mutated gene) and 4) Replicate previous associations from the Tineas Capitas study of meningioma risk with variants in DNA repair genes (KRAS2, ERCC2, CCND1).107 The proposed genetic analyses would represent the first GWAS data for meningioma and also provide important replication of previously observed associations with strong biological plausibility given the established association between meningioma risk and ionizing radiation. Identification of risk loci for meningioma will likely have strong etiologic significance with importance for both prevention and treatment.

项目概要/摘要 脑膜瘤是最常见的原发性脑肿瘤，存在于高达百分之一的成年人中，并且 虽然通常被认为是良性的，但其生存率与乳腺癌相当。风险信息 因素极其有限。为了更好地定义这些因素，我们正在开展一项 全面的基于人群的脑膜瘤病例/对照研究，包括 1600 例病例和 1600 个对照来自马萨诸塞州、康涅狄格州、北卡罗来纳州、加利福尼亚州和德克萨斯州。这 将代表全球最大的基于人群的脑膜瘤病例集合，其中超过 现有研究的病例数量翻倍。我们目前正在收集生物样本， 以及在美国国立卫生研究院 (NIH) 资助下的广泛暴露和表型数据 R01 CA109468、CA109461、CA109745、CA108473 和 CA109475)。在此应用程序中，我们要求 资金对研究对象进行基因分型，以寻找脑膜瘤的遗传风险位点。我们的目标是 1) 使用 1360 个白种人进行脑膜瘤的首次全基因组关联研究 (GWAS) 病例来自我们正在进行的病例/对照项目，以及 3420 例来自上半年的白人对照病例 三个控制系列 a) 来自我们正在进行的案例/控制项目的 600 个控制，b) 来自我们正在进行的案例/控制项目的 1699 个控制 Illumina iControlDB 和 c) 来自癌症易感性遗传标记 (CGEM) 的 1121 个对照 研究，2) 使用从我们的临床系列和研究中抽取的 700 名额外白种人脑膜瘤受试者 上述控制的后半部分 (n=3420)，复制目标 1 中产生的候选者 与脑膜瘤相关性p<10-5。 p < 5.0*10-8 的变体将被视为显着 第一阶段和第二阶段综合分析得出的全基因组与脑膜瘤风险的关联，3) 复制之前 Interphone 研究 8a 中脑膜瘤风险与 BRIP1 变异之间的关联 （乳腺癌易感基因 (BRCA1) 相互作用蛋白）和 ATM（毛细血管扩张性共济失调） 突变基因）和 4）复制先前的 Tineas Capitas 脑膜瘤研究中的关联 DNA 修复基因（KRAS2、ERCC2、CCND1）变异的风险。107 拟议的遗传分析 将代表脑膜瘤的第一个 GWAS 数据，并提供重要的复制 鉴于已建立的关联，先前观察到的关联具有很强的生物学合理性 脑膜瘤风险和电离辐射之间的关系。识别脑膜瘤的风险位点可能会 具有很强的病因学意义，对于预防和治疗都有重要意义。