Risk of meningioma and common variation in genes related to innate immunity.
Risk of meningioma and common variation in genes related to innate immunity.
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DOI：
10.1158/1055-9965.epi-09-1151
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发表时间：
2010-05
期刊：
影响因子：
--
通讯作者：
Inskip PD
中科院分区：
文献类型：
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作者：
Rajaraman P;Brenner AV;Neta G;Pfeiffer R;Wang SS;Yeager M;Thomas G;Fine HA;Linet MS;Rothman N;Chanock SJ;Inskip PD
脑膜瘤是美国第二常见的成人脑肿瘤，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风险。为了确定先天免疫相关基因中脑膜瘤的遗传标记，我们对101例脑膜瘤病例和330例频率匹配的欧洲血统对照进行了一项探索性关联研究，研究对象来自国家癌症研究所进行的一项以医院为基础的研究。我们在HapMap 1中根据高加索人r2> 0.8和次要等位基因频率> 5%选择的148个遗传区域中对1407个“标签”单核苷酸多态性（SNP）进行基因分型。脑膜瘤的风险通过比值比和95%置信区间来估计。分布在12个基因区域的17个SNP（NFKB 1（3）、FCER 1G（3）、CCR 6（2）、VCAM 1、CD 14、TNFRSF 18、RAC 2、XDH、C1 D、TLR 1/TLR 10/TLR 6、NOS 1、DEFA 5）与脑膜瘤的风险相关，p<0.01。虽然在控制多重比较后，单个SNP检验不显著，但基于基因区域的检验对于TNFRSF 18、NFKB 1、FCER 1G、CD 14、C1 D、CCR 6和VCAM 1具有统计学显著性（p<0.05）。我们的研究结果表明，先天免疫基因中常见的遗传多态性可能与脑膜瘤的风险有关。由于样本量小，需要在更大的脑膜瘤研究中重复这些结果。
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 1407 “tag” single nucleotide polymorphisms (SNPs) in 148 genetic regions chosen on the basis of an r2> 0.8 and minor allele frequency > 5% in Caucasians in HapMap1. Risk of meningioma was estimated by odds ratios and 95% confidence intervals. Seventeen SNPs distributed across twelve genetic regions (NFKB1 (3), FCER1G (3), CCR6 (2), VCAM1, CD14, TNFRSF18, RAC2, XDH, C1D, TLR1/TLR10/TLR6, NOS1, DEFA5) were associated with 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.