Human Genetics, Genome Institute of Singapore, Agency for Science, Technology and Research (A*STAR), Singapore.
Nat Genet. 2013 Jul;45(7):804-7. doi: 10.1038/ng.2666. Epub 2013 Jun 9.
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.
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。
