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.

项目总结/摘要 脑膜瘤是最常见的原发性脑肿瘤，在成人中高达1%， 虽然通常被认为是良性的，但其存活率与乳腺癌相当。了解风险 因素是非常有限的。为了更好地确定这些因素，我们正在进行一项 一项基于人群的脑膜瘤病例/对照研究，包括1600例病例， 来自马萨诸塞州、康涅狄格州、北卡罗来纳州、加州和德克萨斯州的1600个对照。这 将代表全世界最大的脑膜瘤病例群， 是现有研究的两倍。我们目前正在收集生物标本， 在美国国立卫生研究院（NIH）的资助下， R 01为CA 109468、CA 109461、CA 109745、CA 108473和CA 109475）。在本申请中，我们要求 基金对研究对象进行基因分型，以发现脑膜瘤的遗传风险位点。我们的目标是1） 使用1360名白人进行第一次脑膜瘤全基因组关联研究（GWAS） 来自我们正在进行的病例/对照项目的3420例病例和来自2009年上半年的3420例白人对照。 三个对照系列a）来自我们正在进行的病例/对照项目的600个对照，B）来自 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中抽取的700名额外的高加索脑膜瘤受试者， 上述对照的第二半（n=3420），来自目标1的重复候选物， p<10-5与脑膜瘤相关。p < 5.0*10-8的变量将被认为是显著的。 1期和2期联合分析的全基因组与脑膜瘤风险的相关性，3） 复制先前来自Interphone研究8a的脑膜瘤风险与BRIP 1变异的相关性 (the乳腺癌易感基因（BRCA 1）相互作用蛋白）和ATM（共济失调毛细血管扩张症 突变基因）和4）复制先前的关联从脑膜瘤的Tineas Capitas研究 DNA修复基因（KRAS 2、ERCC 2、CCND 1）变异的风险。 将代表脑膜瘤的第一个GWAS数据，也提供了重要的复制， 考虑到已建立的关联，先前观察到的关联具有较强的生物相容性 脑膜瘤风险和电离辐射之间的联系脑膜瘤的危险位点的识别将可能 具有很强的病因学意义，对预防和治疗都很重要。