An X-chromosomal association study identifies a susceptibility locus at Xq22.1 for hepatitis B virus-related hepatocellular carcinoma
An X-chromosomal association study identifies a susceptibility locus at Xq22.1 for hepatitis B virus-related hepatocellular carcinoma
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一项 X 染色体关联研究确定了 Xq22.1 上乙型肝炎病毒相关肝细胞癌的易感位点。
DOI：
10.1016/j.clinre.2013.09.002
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发表时间：
2013-12-01
影响因子：
2.7
通讯作者：
Huang, Xiao-Wu
中科院分区：
文献类型：
--
作者：
Jiang, Jia-Hao;Gao, Qiang;Huang, Xiao-Wu
背景与目的：肝细胞癌家系的遗传流行病学研究表明，肝细胞癌易感基因存在X连锁隐性遗传。本研究旨在验证X染色体上存在肝癌易感基因的假设。方法：对从肝癌高发区招募的中国男性进行X染色体关联研究。结果：通过对50例肝癌患者和50例正常对照的5454个X染色体单核苷酸多态(SNPs)的分析，我们发现了两个有希望的SNPs聚集区，分别位于Xq22.1和Xq26.2。我们进一步从这两个区域选择了35个标签SNP(TSNP)，用于在另一组独立的290例病例和242名对照中进行额外的基因分型分析。值得注意的是，Xq22.1位的rs5945919 SNP与乙肝相关性肝细胞癌显著相关(优势比[OR]=2.22，95%可信区间[CI]=1.15~4.30，P=0.016)。用qRT-PCR方法分析了rs5945919基因座附近的RAB40AL、BEX1和Nxf3基因在24例肝癌组织和配对的癌旁肝组织中的表达。结论：Xq22.1是肝癌的新易感基因，而Nxf3是相关肝癌的候选危险因素。(C)2013年爱思唯尔·马森公司。版权所有。
Background and objective: Genetic epidemiological data in hepatocellular carcinoma (HCC) pedigrees indicate a pattern of X-linked recessive inheritance of HCC susceptibility genes. This study is designed to test the hypothesis that there are genes conferring susceptibility to HCC located on the X-chromosome.Methods: An X-chromosomal association study was conducted among Chinese men recruited from an area with a high prevalence of HCC. The candidate gene was further investigated by quantitative reverse transcription-polymerase chain reaction (qRT-PCR).Results: By analyzing 5454 X-chromosome single nucleotide polymorphisms (SNPs) in 50 HCC patients and 50 controls, we found two promising regions in which the associated SNPs clustered, located at Xq22.1 and Xq26.2. We further selected 35 tag SNPs (tSNPs) from these two regions for additional genotyping analysis in another independent set of 290 cases and 242 controls. Notably, SNP rs5945919 at Xq22.1 exhibited a significant association with HBV-related HCC (odds ratio [OR] = 2.22, 95% confidence interval [CI] = 1.15-4.30, P = 0.016). The expressions of the three genes near the rs5945919 locus, RAB40AL, BEX1, and NXF3, were analyzed by qRT-PCR between another 24 HCC tissues and paired peritumoral liver tissues. The results indicated that NXF3, rather than RAB40AL and BEX1, mRNA level was found to be more abundant in HCC tissuethan in peritumoral liver tissue.Conclusions: Our findings implicated Xq22.1 as a novel susceptibility locus for HCC and NXF3 as a candidate risk factor for relevant HCC. (C) 2013 Elsevier Masson SAS. All rights reserved.