Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, the University of Tokyo, Tokyo, Japan.
J Hum Genet. 2011 Jun;56(6):436-9. doi: 10.1038/jhg.2011.35. Epub 2011 Apr 7.
Diffuse large B-cell lymphoma (DLBCL) is one of the most aggressive cancers of B-lymphocytes. To investigate genetic susceptibility factors for DLBCL, we performed single-nucleotide polymorphism based genome-wide association study (GWAS) in a total of 399 DLBCL cases and 4243 controls of Japanese population. By following two-stage GWAS approach and an independent replication study, we identified disease susceptibility locus within intron 3 of the CDC42BPB gene on 14q32 (rs751837; P=3.30 × 10(-7) and odds ratio (OR) of 3.5), a region of frequent chromosomal translocations in lymphoma, and variant on 13q12 (rs7097; P=6.57 × 10(-6) and OR of 1.43) which harbors the notch signaling mediator, LNX2 gene. Our findings would contribute to the understanding of DLBCL risk and also may lead to the elucidation of its molecular pathogenesis.
弥漫性大 B 细胞淋巴瘤（DLBCL）是最具侵袭性的 B 淋巴细胞癌之一。为了研究 DLBCL 的遗传易感性因素，我们在日本人群中对总共 399 例 DLBCL 病例和 4243 例对照进行了基于单核苷酸多态性的全基因组关联研究（GWAS）。通过两阶段 GWAS 方法和独立的复制研究，我们在淋巴瘤中频繁染色体易位的 14q32 上的 CDC42BPB 基因内含子 3 内（rs751837；P=3.30×10(-7)，优势比（OR）为 3.5）和包含 notch 信号介质 LNX2 基因的 13q12 上（rs7097；P=6.57×10(-6)，OR 为 1.43）确定了疾病易感性位点。我们的发现将有助于理解 DLBCL 的风险，也可能阐明其分子发病机制。
