A genome-wide association study of nasopharyngeal carcinoma identifies three new susceptibility loci
A genome-wide association study of nasopharyngeal carcinoma identifies three new susceptibility loci
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DOI：
10.1038/ng.601
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发表时间：
2010-07-01
期刊：
影响因子：
30.8
通讯作者：
Zeng, Yi-Xin
中科院分区：
文献类型：
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作者：
Bei, Jin-Xin;Li, Yi;Zeng, Yi-Xin
为了确定鼻咽癌（NPC）的遗传易感性位点，研究人员在1583例鼻咽癌患者和1894例中国南方血统的对照人群中使用464,328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3507例病例和3063例对照中进行了基因分型。通过对广东279对三胞胎的传播不平衡检验分析，进一步证实了这7个支持性snp。我们发现了3个新的易感位点，分别是13q12上的TNFRSF19 (rs9510787, P-combined = 1.53 × 10（-9)，比值比(OR) = 1.20）、3q26上的MDS1-EVI1 （rs6774494, P-combined = 1.34 × 10(-8), OR = 0.84）和9p21上的CDKN2A-CDKN2B基因簇（rs1412829, P-combined = 4.84 × 10(-7), OR = 0.78）。此外，我们通过揭示rs2860580 （P-combined = 4.88 × 10(-67), OR = 0.58）、rs2894207 （P-combined = 3.42 × 10(-33), OR = 0.61）和rs28421666 （P-combined = 2.49 × 10(-18), OR = 0.67）的独立相关性，证实了HLA的作用。我们的研究结果通过强调除了HLA分子外与TNFRSF19和MDS1-EVI1相关的通路的参与，为NPC的发病机制提供了新的见解。
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, P-combined = 1.53 x 10(-9), odds ratio (OR) = 1.20), MDS1-EVI1 on 3q26 (rs6774494, P-combined = 1.34 x 10(-8), OR = 0.84) and the CDKN2A-CDKN2B gene cluster on 9p21 (rs1412829, P-combined = 4.84 x 10(-7), OR = 0.78). Furthermore, we confirmed the role of HLA by revealing independent associations at rs2860580 (P-combined = 4.88 x 10(-67), OR = 0.58), rs2894207 (P-combined = 3.42 x 10(-33), OR = 0.61) and rs28421666 (P-combined = 2.49 x 10(-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.