Risk of meningioma and common variation in genes related to innate immunity.

BACKGROUND

The etiology of meningioma, the second most common type of adult brain tumor in the United States, is largely unknown. Prior studies indicate that history of immune-related conditions may affect the risk of meningioma.

METHODS

To identify genetic markers for meningioma in genes involved with innate immunity, we conducted an exploratory association study of 101 meningioma cases and 330 frequency-matched controls of European ancestry using subjects from a hospital-based study conducted by the National Cancer Institute. We genotyped 1,407 "tag" single nucleotide polymorphisms (SNP) in 148 genetic regions chosen on the basis of an r2>0.8 and minor allele frequency of >5% in Caucasians in HapMap1. Risk of meningioma was estimated by odds ratios and 95% confidence intervals.

RESULTS

Seventeen SNPs distributed across 12 genetic regions (NFKB1 (3), FCER1G (3), CCR6 (2), VCAM1, CD14, TNFRSF18, RAC2, XDH, C1D, TLR1/TLR10/TLR6, NOS1, and DEFA5) were associated with the risk of meningioma with P<0.01. Although individual SNP tests were not significant after controlling for multiple comparisons, gene region-based tests were statistically significant (P<0.05) for TNFRSF18, NFKB1, FCER1G, CD14, C1D, CCR6, and VCAM1.

CONCLUSIONS AND IMPACT: Our results indicate that common genetic polymorphisms in innate immunity genes may be associated with risk of meningioma. Given the small sample size, replication of these results in a larger study of meningioma is needed.