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全基因组关联研究揭示 3q27 区域是中国人群 B 细胞非霍奇金淋巴瘤的易感性位点。

Genome-wide association study of B cell non-Hodgkin lymphoma identifies 3q27 as a susceptibility locus in the Chinese population.

机构信息

Human Genetics, Genome Institute of Singapore, Agency for Science, Technology and Research (A*STAR), Singapore.

出版信息

Nat Genet. 2013 Jul;45(7):804-7. doi: 10.1038/ng.2666. Epub 2013 Jun 9.

Abstract

To identify genetic risk factors underlying non-Hodgkin lymphomas (NHLs) from the B cell lineage, we conducted a genome-wide association study (GWAS) of 253 Chinese individuals with B cell NHL (cases) and 1,438 controls and further validation in 1,175 cases and 5,492 controls. We identified a new susceptibility locus, rs6773854, located between BCL6 (encoding B cell lymphoma protein 6) and LPP (encoding lipoma preferred partner) on oncogene-rich chromosome 3q27 that was significantly associated with increased risk of B cell NHL (meta-analysis P = 3.36 × 10⁻¹³, per-allele odds ratio (OR) = 1.44) and with diffuse large B cell lymphoma (DLBCL) in particular (meta-analysis P = 1.14 × 10⁻¹¹, OR = 1.47). We found no evidence of association of rs6773854 with non-B cell NHLs (T cell and natural killer (NK) lineages) (P = 0.17, OR = 1.12) and observed significant heterogeneity between B cell and non-B cell subtypes (Phet = 0.01, I² = 84%). Our results provide insight that germline variation in the intergenic region between BCL6 and LPP has a role in risk of B cell lymphomagenesis.

摘要

为了确定 B 细胞谱系非霍奇金淋巴瘤(NHL)的遗传风险因素,我们对 253 名中国 B 细胞 NHL 患者(病例)和 1438 名对照者进行了全基因组关联研究(GWAS),并在 1175 名病例和 5492 名对照者中进行了进一步验证。我们发现了一个新的易感位点 rs6773854,位于 BCL6(编码 B 细胞淋巴瘤蛋白 6)和 LPP(编码脂肪肉瘤优先伙伴)之间的癌基因丰富的 3q27 染色体上,与 B 细胞 NHL(荟萃分析 P = 3.36×10⁻¹³,每个等位基因的优势比(OR)=1.44)和弥漫性大 B 细胞淋巴瘤(DLBCL)风险增加显著相关(荟萃分析 P = 1.14×10⁻¹¹,OR = 1.47)。我们没有发现 rs6773854 与非 B 细胞 NHL(T 细胞和自然杀伤(NK)谱系)之间存在关联的证据(P = 0.17,OR = 1.12),并且在 B 细胞和非 B 细胞亚型之间观察到显著的异质性(Phet = 0.01,I² = 84%)。我们的研究结果表明,BCL6 和 LPP 之间的基因间区域的种系变异在 B 细胞淋巴瘤发生风险中起作用。

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