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.
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.
| Aizer, Ayal A; Arvold, Nils D; Catalano, Paul et al. (2014) Adjuvant radiation therapy, local recurrence, and the need for salvage therapy in atypical meningioma. Neuro Oncol 16:1547-53 |
| Schildkraut, Joellen M; Calvocoressi, Lisa; Wang, Frances et al. (2014) Endogenous and exogenous hormone exposure and the risk of meningioma in men. J Neurosurg 120:820-6 |
| Claus, Elizabeth B; Wiemels, Joseph; Wrensch, Margaret (2013) Dental x-rays and risk of meningioma: response to Drs. Calnon, Jorgensen, and White. Cancer 119:465-6 |
| Wiemels, Joseph L; Bracci, Paige M; Wrensch, Margaret et al. (2013) Assessment of autoantibodies to meningioma in a population-based study. Am J Epidemiol 177:75-83 |
| Claus, Elizabeth B; Calvocoressi, Lisa; Bondy, Melissa L et al. (2013) Exogenous hormone use, reproductive factors, and risk of intracranial meningioma in females. J Neurosurg 118:649-56 |
| Claus, Elizabeth B; Walsh, Kyle M; Calvocoressi, Lisa et al. (2012) Cigarette smoking and risk of meningioma: the effect of gender. Cancer Epidemiol Biomarkers Prev 21:943-50 |
| Claus, Elizabeth B; Calvocoressi, Lisa; Bondy, Melissa L et al. (2012) Dental x-rays and risk of meningioma. Cancer 118:4530-7 |
| Claus, Elizabeth B; Calvocoressi, Lisa; Bondy, Melissa L et al. (2011) Family and personal medical history and risk of meningioma. J Neurosurg 115:1072-7 |
| Wiemels, Joseph L; Wrensch, Margaret; Sison, Jennette D et al. (2011) Reduced allergy and immunoglobulin E among adults with intracranial meningioma compared to controls. Int J Cancer 129:1932-9 |
| Cahill, Kevin S; Claus, Elizabeth B (2011) Treatment and survival of patients with nonmalignant intracranial meningioma: results from the Surveillance, Epidemiology, and End Results Program of the National Cancer Institute. Clinical article. J Neurosurg 115:259-67 |
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