Further evidence for the existence of major susceptibility of nasopharyngeal carcinoma in the region near HLA-A locus in Southern Chinese.

Further evidence for the existence of major susceptibility of nasopharyngeal carcinoma in the region near HLA-A locus in Southern Chinese.
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进一步证明中国南方人HLA-A基因座附近存在鼻咽癌的高易感性

DOI:
10.1186/1479-5876-10-57
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发表时间:
2012-03-22
影响因子:
7.4
通讯作者:
Li X
Li X
中科院分区:
医学2区
文献类型:
--
作者:
Zhao M;Cai H;Li X;Zheng H;Yang X;Fang W;Zhang L;Wei G;Li M;Yao K;Li X

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鼻咽癌(Nasopharyngeal carcinoma,NPC)是一种多因素恶性肿瘤,与环境因素、遗传因素和EB病毒感染密切相关。人类白细胞抗原(human leukocyte antigen,HLA)复合物,特别是HLA-A位点附近的区域,被认为是鼻咽癌遗传易感性位点的主要候选区域,包括最近的两项全基因组关联(genome wide association,GWA)研究。为了在前人研究的基础上进一步证明HLA-A位点附近地区鼻咽癌的易感性,我们对广东省535例散发性鼻咽癌患者和525例无癌对照者进行了两阶段的病例对照研究,方法应用Heploview软件从HLA-A位点附近片段中筛选出38个标签SNPs(从D 6S 211到D 6S 510),并在GenomeLab SNPstream平台上对第1阶段中的206例病例和180例对照进行基因分型。随后,在另一个平台上(Sequenom iPlex Assay)在另一组独立的研究人群(包括329例病例和345名对照)中检测第1阶段显著的SNPs和17个额外的SNPs。两个最重要的SNPs(rs 9260734和rs 2517716)分别位于HLA-A和HCG 9附近,与之前两项GWA研究报道的该区域的其他一些SNPs存在强LD。同时发现了与HLA-G相近的新的独立易感基因位点(rs 9404952,Pcombined = 6.6 × 10-5,OR combined = 1.45)。结论HLA复合体区D 6S 211 ~ D 6S 510可能含有鼻咽癌易感基因,有待进一步研究。
BackgroundNasopharyngeal carcinoma (NPC) is a multi-factorial malignancy closely associated with environmental factors, genetic factors and Epstein-Barr virus infection. Human leukocyte antigen (HLA) complex, specially the region near HLA-A locus, was regarded as a major candidate region bearing NPC genetic susceptibility loci in many previous studies including two recent genome-wide association (GWA) studies. To provide further evidence for the NPC susceptibility in the region near HLA-A locus based on other previous studies, we carried out a two-stage hospital-based case control association study including 535 sporadic NPC patients and 525 cancer-free control subjects from Guangdong, a high prevalence area of NPC in China.Methods38 tag SNPs were initially selected by Heploview from the segment around HLA-A locus (from D6S211 to D6S510) and genotyped on GenomeLab SNPstream platform in 206 cases and 180 controls in the stage 1. Subsequently, the stage 1 significant SNPs and 17 additional SNPs were examined on another platform (Sequenom iPlex Assay) in another independent set of study population including 329 cases and 345 controls.ResultsTotally eight SNPs from the segment from D6S211 to D6S510 within HLA complex were found to be significantly associated with NPC. Two of the most significant SNPs (rs9260734 and rs2517716) located near to HLA-A and HCG9 respectively were in strong LD with some other SNPs of this region reported by two previous GWA studies. Meanwhile, Meanwhile, novel independent susceptibility loci (rs9404952, Pcombined = 6.6 × 10-5, OR combined = 1.45) was found to be close to HLA-G.ConclusionTherefore, our present study supports that the segment from D6S211 to D6S510 in HLA complex region might contain NPC susceptibility loci which indeed needs to be fully investigated in the future.
DOI: 10.1038/gene.2009.109
发表时间: 2010-06
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