State Key Laboratory of Oncology in Southern China, Guangzhou, China.
Nat Genet. 2010 Jul;42(7):599-603. doi: 10.1038/ng.601. Epub 2010 May 30.
To identify genetic susceptibility loci for nasopharyngeal carcinoma (NPC), a genome-wide association study was performed using 464,328 autosomal SNPs in 1,583 NPC affected individuals (cases) and 1,894 controls of southern Chinese descent. The top 49 SNPs from the genome-wide association study were genotyped in 3,507 cases and 3,063 controls of southern Chinese descent from Guangdong and Guangxi. The seven supportive SNPs were further confirmed by transmission disequilibrium test analysis in 279 trios from Guangdong. We identified three new susceptibility loci, TNFRSF19 on 13q12 (rs9510787, Pcombined=1.53x10(-9), odds ratio (OR)=1.20), MDS1-EVI1 on 3q26 (rs6774494, Pcombined=1.34x10(-8), OR=0.84) and the CDKN2A-CDKN2B gene cluster on 9p21 (rs1412829, Pcombined=4.84x10(-7), OR=0.78). Furthermore, we confirmed the role of HLA by revealing independent associations at rs2860580 (Pcombined=4.88x10(-67), OR=0.58), rs2894207 (Pcombined=3.42x10(-33), OR=0.61) and rs28421666 (Pcombined=2.49x10(-18), OR=0.67). Our findings provide new insights into the pathogenesis of NPC by highlighting the involvement of pathways related to TNFRSF19 and MDS1-EVI1 in addition to HLA molecules.
为了鉴定鼻咽癌（NPC）的遗传易感性基因座，我们对 1583 名 NPC 患者（病例）和 1894 名中国南方裔对照者的 464328 个常染色体 SNP 进行了全基因组关联研究。从全基因组关联研究中获得的前 49 个 SNP 在来自广东和广西的 3507 名中国南方裔病例和 3063 名对照者中进行了基因分型。在广东的 279 个三口中，通过传递不平衡测试分析进一步确认了 7 个支持性 SNP。我们鉴定出了三个新的易感基因座，13q12 上的 TNFRSF19（rs9510787，Pcombined=1.53x10(-9)，比值比（OR）=1.20）、3q26 上的 MDS1-EVI1（rs6774494，Pcombined=1.34x10(-8)，OR=0.84）和 9p21 上的 CDKN2A-CDKN2B 基因簇（rs1412829，Pcombined=4.84x10(-7)，OR=0.78）。此外，我们通过揭示 HLA 中的独立关联 rs2860580（Pcombined=4.88x10(-67)，OR=0.58）、rs2894207（Pcombined=3.42x10(-33)，OR=0.61）和 rs28421666（Pcombined=2.49x10(-18)，OR=0.67），证实了 HLA 的作用。我们的研究结果通过强调 TNFRSF19 和 MDS1-EVI1 相关途径以及 HLA 分子在 NPC 发病机制中的参与，为 NPC 的发病机制提供了新的见解。
