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.
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