Université Pierre et Marie Curie-Paris 6, Centre de Recherche de l’Institut du Cerveau et de la Moëlle épinière/UMR-S975, GH Pitié-Salpêtrière, 47 boulevard de l'Hôpital, Paris, France.
Hum Mol Genet. 2011 Jul 15;20(14):2897-904. doi: 10.1093/hmg/ddr192. Epub 2011 Apr 29.
While gliomas are the most common primary brain tumors, their etiology is largely unknown. To identify novel risk loci for glioma, we conducted genome-wide association (GWA) analysis of two case-control series from France and Germany (2269 cases and 2500 controls). Pooling these data with previously reported UK and US GWA studies provided data on 4147 glioma cases and 7435 controls genotyped for 424 460 common tagging single-nucleotide polymorphisms. Using these data, we demonstrate two statistically independent associations between glioma and rs11979158 and rs2252586, at 7p11.2 which encompasses the EGFR gene (population-corrected statistics, P(c) = 7.72 × 10(-8) and 2.09 × 10(-8), respectively). Both associations were independent of tumor subtype, and were independent of EGFR amplification, p16INK4a deletion and IDH1 mutation status in tumors; compatible with driver effects of the variants on glioma development. These findings show that variation in 7p11.2 is a determinant of inherited glioma risk.
虽然神经胶质瘤是最常见的原发性脑肿瘤，但它们的病因在很大程度上仍是未知的。为了确定神经胶质瘤的新的风险基因座，我们对来自法国和德国的两个病例对照系列进行了全基因组关联（GWA）分析（2269 例病例和 2500 例对照）。将这些数据与先前报道的英国和美国的 GWA 研究数据进行合并，为 4147 例神经胶质瘤病例和 7435 例接受 424460 个常见标记单核苷酸多态性基因分型的对照提供了数据。利用这些数据，我们证明了神经胶质瘤与 7p11.2 上的 rs11979158 和 rs2252586 之间存在两个统计学上独立的关联，该区域包含 EGFR 基因（经人群校正的统计学，P(c)分别为 7.72×10(-8)和 2.09×10(-8)）。这两个关联与肿瘤亚型无关，与肿瘤中 EGFR 扩增、p16INK4a 缺失和 IDH1 突变状态无关；这与变体对神经胶质瘤发展的驱动作用一致。这些发现表明 7p11.2 上的变异是遗传性神经胶质瘤风险的决定因素。
