Division of Cancer Epidemiology and Genetics, Neuro-oncology Branch, National Cancer Institute, NIH, Department of Health and Human Services, 6120 Executive Boulevard, EPS Room 7058, Bethesda, MD 20892-7238, USA.
Cancer Epidemiol Biomarkers Prev. 2010 May;19(5):1356-61. doi: 10.1158/1055-9965.EPI-09-1151. Epub 2010 Apr 20.
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.
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.
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.
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.
脑膜瘤是美国第二大常见的成人脑肿瘤，其病因在很大程度上尚不清楚。先前的研究表明，免疫相关疾病史可能会影响脑膜瘤的发病风险。
为了在参与固有免疫的基因中找到脑膜瘤的遗传标志物，我们对来自美国国立癌症研究所进行的一项基于医院的研究中的 101 例脑膜瘤病例和 330 例频数匹配对照进行了探索性关联研究。我们在 HapMap1 中选择了基于 r2>0.8 和高加索人群中次要等位基因频率>5%的 148 个遗传区域的 1,407 个“标签”单核苷酸多态性（SNP）进行基因分型。通过比值比和 95%置信区间来估计脑膜瘤的发病风险。
17 个 SNP 分布在 12 个遗传区域（NFKB1（3）、FCER1G（3）、CCR6（2）、VCAM1、CD14、TNFRSF18、RAC2、XDH、C1D、TLR1/TLR10/TLR6、NOS1 和 DEFA5）与脑膜瘤的发病风险相关（P<0.01）。虽然在进行多次比较校正后，单个 SNP 检验没有统计学意义，但基于基因区域的检验在 TNFRSF18、NFKB1、FCER1G、CD14、C1D、CCR6 和 VCAM1 中具有统计学意义（P<0.05）。
我们的研究结果表明，固有免疫基因中的常见遗传多态性可能与脑膜瘤的发病风险相关。鉴于样本量较小，需要在更大的脑膜瘤研究中对这些结果进行复制。
