Genome-wide association study of hepatocellular carcinoma in Southern Chinese patients with chronic hepatitis B virus infection.
Genome-wide association study of hepatocellular carcinoma in Southern Chinese patients with chronic hepatitis B virus infection.
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DOI：
10.1371/journal.pone.0028798
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Ng IO
中科院分区：
文献类型：
--
作者：
Chan KY;Wong CM;Kwan JS;Lee JM;Cheung KW;Yuen MF;Lai CL;Poon RT;Sham PC;Ng IO
慢性乙型肝炎病毒（HBV）感染是肝细胞癌（HCC）发展最相关的危险因素之一，但只有一小部分慢性HBV携带者发展为HCC，这表明病毒、环境和遗传因素之间的复杂相互作用导致HBV感染患者发生HCC。到目前为止，宿主遗传因素尚未完全被表征。因此，我们使用Illumina Human610-Quad BeadChips在中国南方的一个队列中进行了一项全基因组关联（GWA）研究，该队列包括95名hbv感染的HCC患者（病例）和97名未感染HCC的hbv感染患者（对照组）。然后在500例病例和728例对照的独立队列中验证了顶级单核苷酸多态性（snp）。8p12染色体上的4个snp （rs12682266、rs7821974、rs2275959、rs1573266）在GWA期和复制期均表现出一致的相关性（ORcombined = 1.31-1.39; pcombined = 2.71×10−5-5.19×10−4;PARcombined = 26-31%）。我们利用计算机数据挖掘在该区域发现了一个2.3 kb的表达序列标签（EST），并通过实验验证了全长EST的存在。与相应的非肿瘤肝组织相比，人类HCC肿瘤中EST的表达水平显著降低（P<0.001）。序列分析和体外蛋白翻译研究结果表明，该转录物可能具有长链非编码RNA的功能。总之，我们的研究提示8p12染色体变异可能促进HBV患者发生HCC。进一步研究该区域的功能可能有助于了解hbv相关的肝癌发生。
One of the most relevant risk factors for hepatocellular carcinoma (HCC) development is chronic hepatitis B virus (HBV) infection, but only a fraction of chronic HBV carriers develop HCC, indicating that complex interactions among viral, environmental and genetic factors lead to HCC in HBV-infected patients. So far, host genetic factors have incompletely been characterized. Therefore, we performed a genome-wide association (GWA) study in a Southern Chinese cohort consisting of 95 HBV-infected HCC patients (cases) and 97 HBV-infected patients without HCC (controls) using the Illumina Human610-Quad BeadChips. The top single nucleotide polymorphisms (SNPs) were then validated in an independent cohort of 500 cases and 728 controls. 4 SNPs (rs12682266, rs7821974, rs2275959, rs1573266) at chromosome 8p12 showed consistent association in both the GWA and replication phases (ORcombined = 1.31–1.39; pcombined = 2.71×10−5–5.19×10−4; PARcombined = 26–31%). We found a 2.3-kb expressed sequence tag (EST) in the region using in-silico data mining and verified the existence of the full-length EST experimentally. The expression level of the EST was significantly reduced in human HCC tumors in comparison to the corresponding non-tumorous liver tissues (P<0.001). Results from sequence analysis and in-vitro protein translation study suggest that the transcript might function as a long non-coding RNA. In summary, our study suggests that variations at chromosome 8p12 may promote HCC in patients with HBV. Further functional studies of this region may help understand HBV-associated hepatocarcinogenesis.
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影响因子：
13.5
作者：
Lee, Terence Kin Wah;Castilho, Antonia;Ng, Irene Oi Lin
通讯作者：
Ng, Irene Oi Lin
影响因子：
64.8
作者：
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影响因子：
64.8
作者：
Gong, Chenguang;Maquat, Lynne E.
通讯作者：
Maquat, Lynne E.
影响因子：
23.4
作者：
Aly, Markus;Wiklund, Fredrik;Xu, Jianfeng;Isaacs, William B.;Eklund, Martin;D'Amato, Mauro;Adolfsson, Jan;Gronberg, Henrik
通讯作者：
Gronberg, Henrik
DOI：
10.1186/bcr2608
发表时间：
2010
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Arason A;Gunnarsson H;Johannesdottir G;Jonasson K;Bendahl PO;Gillanders EM;Agnarsson BA;Jönsson G;Pylkäs K;Mustonen A;Heikkinen T;Aittomäki K;Blomqvist C;Melin B;Johannsson OT;Møller P;Winqvist R;Nevanlinna H;Borg A;Barkardottir RB
通讯作者：
Barkardottir RB