Division of Genetics and Epidemiology, Institute of Cancer Research, Sutton, Surrey SM2 5NG, UK.
Nat Commun. 2013;4:2549. doi: 10.1038/ncomms3549.
In addition to HLA, recent genome-wide association studies (GWASs) of Hodgkin's lymphoma (HL) have identified susceptibility loci for HL at 2p16.1, 8q24.21 and 10p14. In this study, we perform a GWAS meta-analysis with published GWAS (totalling 1,465 cases and 6,417 controls of European background), and follow-up the most significant association signals in 2,024 cases and 1,853 controls. A combined analysis identifies new HL susceptibility loci mapping to 3p24.1 (rs3806624; P=1.14 × 10(-12), odds ratio (OR)=1.26) and 6q23.3 (rs7745098; P=3.42 × 10(-9), OR=1.21). rs3806624 localizes 5' to the EOMES (eomesodermin) gene within a p53 response element affecting p53 binding. rs7745098 maps intergenic to HBS1L and MYB, a region previously associated with haematopoiesis. These findings provide further insight into the genetic and biological basis of inherited susceptibility to HL.
除了 HLA 之外,最近对霍奇金淋巴瘤 (HL) 的全基因组关联研究 (GWAS) 已经确定了 HL 在 2p16.1、8q24.21 和 10p14 上的易感性位点。在这项研究中,我们对已发表的 GWAS 进行了 GWAS 荟萃分析(共包括 1465 例病例和 6417 例对照,均为欧洲背景),并对 2024 例病例和 1853 例对照中的最显著关联信号进行了随访。综合分析确定了新的 HL 易感性位点,位于 3p24.1(rs3806624;P=1.14×10(-12),比值比(OR)=1.26)和 6q23.3(rs7745098;P=3.42×10(-9),OR=1.21)。rs3806624 位于 EOMES(eomesodermin)基因的 5'端,该基因位于影响 p53 结合的 p53 反应元件内。rs7745098 位于 HBS1L 和 MYB 之间的基因间区,该区域先前与造血相关。这些发现为遗传易感性 HL 的遗传和生物学基础提供了进一步的见解。