一项对霍奇金淋巴瘤的荟萃分析显示，19p13.3染色体上的TCF3是一个新的易感基因座。
A meta-analysis of Hodgkin lymphoma reveals 19p13.3 TCF3 as a novel susceptibility locus.
作者信息
Cozen W, Timofeeva M N, Li D, Diepstra A, Hazelett D, Delahaye-Sourdeix M, Edlund C K, Franke L, Rostgaard K, Van Den Berg D J, Cortessis V K, Smedby K E, Glaser S L, Westra H-J, Robison L L, Mack T M, Ghesquieres H, Hwang A E, Nieters A, de Sanjose S, Lightfoot T, Becker N, Maynadie M, Foretova L, Roman E, Benavente Y, Rand K A, Nathwani B N, Glimelius B, Staines A, Boffetta P, Link B K, Kiemeney L, Ansell S M, Bhatia S, Strong L C, Galan P, Vatten L, Habermann T M, Duell E J, Lake A, Veenstra R N, Visser L, Liu Y, Urayama K Y, Montgomery D, Gaborieau V, Weiss L M, Byrnes G, Lathrop M, Cocco P, Best T, Skol A D, Adami H-O, Melbye M, Cerhan J R, Gallagher A, Taylor G M, Slager S L, Brennan P, Coetzee G A, Conti D V, Onel K, Jarrett R F, Hjalgrim H, van den Berg A, McKay J D
机构信息
1] USC Keck School of Medicine, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California 90089-9175, USA [2].
1] International Agency for Research on Cancer (IARC), 69372 Lyon, France [2] Institute of Genetics and Molecular Medicine, University of Edinburgh, EH4 2XU Edinburgh, UK [3].
出版信息
Nat Commun. 2014 Jun 12;5:3856. doi: 10.1038/ncomms4856.
Recent genome-wide association studies (GWAS) of Hodgkin lymphoma (HL) have identified associations with genetic variation at both HLA and non-HLA loci; however, much of heritable HL susceptibility remains unexplained. Here we perform a meta-analysis of three HL GWAS totaling 1,816 cases and 7,877 controls followed by replication in an independent set of 1,281 cases and 3,218 controls to find novel risk loci. We identify a novel variant at 19p13.3 associated with HL (rs1860661; odds ratio (OR)=0.81, 95% confidence interval (95% CI) = 0.76-0.86, P(combined) = 3.5 × 10(-10)), located in intron 2 of TCF3 (also known as E2A), a regulator of B- and T-cell lineage commitment known to be involved in HL pathogenesis. This meta-analysis also notes associations between previously published loci at 2p16, 5q31, 6p31, 8q24 and 10p14 and HL subtypes. We conclude that our data suggest a link between the 19p13.3 locus, including TCF3, and HL risk.
近期针对霍奇金淋巴瘤（HL）的全基因组关联研究（GWAS）已确定其与HLA和非HLA基因座的遗传变异有关联；然而，大部分可遗传的HL易感性仍无法解释。在此，我们对三项HL的GWAS进行荟萃分析，共纳入1816例病例和7877例对照，随后在另一组独立的1281例病例和3218例对照中进行重复验证，以寻找新的风险基因座。我们在19p13.3处鉴定出一个与HL相关的新变异（rs1860661；优势比（OR）=0.81，95%置信区间（95%CI）=0.76 - 0.86，合并P值 = 3.5×10⁻¹⁰），该变异位于TCF3（也称为E2A）的内含子2中，TCF3是B细胞和T细胞谱系定向分化的调节因子，已知其参与HL的发病机制。该荟萃分析还指出，先前报道的位于2p16、5q31、6p31、8q24和10p14的基因座与HL亚型之间存在关联。我们得出结论，我们的数据表明包括TCF3在内的19p13.3基因座与HL风险之间存在联系。
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