The Meningioma Consortium: Genome-Wide Association Study

脑膜瘤联盟：全基因组关联研究

• 批准号: 8089585
• 负责人: Elizabeth B. Claus
• 金额: $ 53.27万
• 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 2013-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8089585
• 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; 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; public health relevance; sex; tumor

DESCRIPTION (provided by applicant): 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. PUBLIC HEALTH RELEVANCE: 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. In this application we request funds to perform the first genome wide association study (GWAS) for meningioma using 2060 case subjects and 6833 control subjects 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.

描述（由申请人提供）：脑膜瘤是最常见的原发性脑肿瘤，最多是1％的成年人，尽管经常被认为是良性，但其生存与乳腺癌相当。有关风险因素的信息极为有限。为了更好地定义此类因素，我们正在进行一项基于人群的脑膜瘤病例/对照研究，其中包括1600例病例和1600例来自马萨诸塞州，康涅狄格州，北卡罗来纳州，加利福尼亚州和德克萨斯州的控制。这将代表全球最大的基于人群的脑膜瘤病例，其数量是任何现有研究的两倍以上。我们目前正在收集生物学标本，以及来自国立卫生研究院的资金（NIH R01S CA109468，CA109461，CA109745，CA108473和CA109475）的广泛接触和表型数据。在此应用中，我们要求资金基因型研究对象，以找到脑膜瘤的遗传风险基因座。 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 （CGEM）研究，2）使用700名来自我们临床系列的其他高加索脑膜瘤受试者和上述对照组的下半部分（n = 3420），从AIM 1中复制候选者，该候选者与脑膜瘤相关。 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 DNA修复基因中脑膜瘤风险的Tineas Capitas研究（KRAS2，ERCC2，CCND1）。107拟议的遗传分析将代表脑膜瘤的第一个GWAS数据，同时脑膜瘤的脑膜瘤数据具有重要的重复，并在脑化较高的渗透率之间具有强大的生物学性相关性，并提供了先前观察到的与牢固的生物学性相关性的相关性。鉴定脑膜瘤的风险基因座可能具有强大的病因学意义，对于预防和治疗都重要。 公共卫生相关性：脑膜瘤是最常见的原发性脑肿瘤，最多有1％的成年人，尽管经常被认为是良性，但其生存与乳腺癌相当。在此应用中，我们要求资金使用2060名病例受试者和6833个对照受试者进行首个基因组广泛的关联研究（GWAS），以对脑膜瘤进行脑膜瘤，并为脑膜炎风险和电离辐射之间的既定生物学合理性提供了重要的复制。鉴定脑膜瘤的风险基因座可能具有强大的病因学意义，对于预防和治疗都重要。