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.

项目摘要/摘要