Genetic variations at loci involved in the immune response are risk factors for hepatocellular carcinoma.
Genetic variations at loci involved in the immune response are risk factors for hepatocellular carcinoma.
复制标题
与免疫反应有关的基因座的遗传变异是肝细胞癌的危险因素。
DOI：
10.1002/hep.23943
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发表时间：
2010-12
期刊：
影响因子：
--
通讯作者：
Buetow KH
中科院分区：
文献类型：
--
作者：
Clifford RJ;Zhang J;Meerzaman DM;Lyu MS;Hu Y;Cultraro CM;Finney RP;Kelley JM;Efroni S;Greenblum SI;Nguyen CV;Rowe WL;Sharma S;Wu G;Yan C;Zhang H;Chung YH;Kim JA;Park NH;Song IH;Buetow KH
Primary liver cancer is the third most common cause of cancer-related death worldwide, with a rising incidence in Western countries. Little is known about the genetic etiology of this disease. To identify genetic factors associated with hepatocellular carcinoma (HCC) and liver cirrhosis (LC), we conducted a comprehensive, genome-wide variation analysis in a population of unrelated Asian individuals. Copy number variation (CNV) and single nucleotide polymorphisms (SNPs) were assayed in peripheral blood with the high-density Affymetrix SNP6.0 microarray platform. We used a two-stage discovery and replication design to control for overfitting and to validate observed results. We identified a strong association with CNV at the T-cell receptor gamma and alpha loci (P < 1 × 10−15) in HCC cases when contrasted with controls. This variation appears to be somatic in origin, reflecting differences between T-cell receptor processing in lymphocytes from individuals with liver disease and healthy individuals that is not attributable to chronic hepatitis virus infection. Analysis of constitutional variation identified three susceptibility loci including the class II MHC complex, whose protein products present antigen to T-cell receptors and mediate immune surveillance. Statistical analysis of biologic networks identified variation in the “antigen presentation and processing” pathway as being highly significantly associated with HCC (P = 1 × 10−11). SNP analysis identified two variants whose allele frequencies differ significantly between HCC and LC. One of these (P = 1.74 × 10−12) lies in the PTEN homolog TPTE2. Combined analysis of CNV, individual SNPs, and pathways suggest that HCC susceptibility is mediated by germline factors affecting the immune response and differences in T-cell receptor processing.
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影响因子：
3.8
作者：
Han W;Han MR;Kang JJ;Bae JY;Lee JH;Bae YJ;Lee JE;Shin HJ;Hwang KT;Hwang SE;Kim SW;Noh DY
通讯作者：
Noh DY
影响因子：
--
作者：
Jeon, Jae-Pil;Shim, Sung-Mi;Han, Bok-Ghee
通讯作者：
Han, Bok-Ghee
影响因子：
2.1
作者：
Olshen, AB;Venkatraman, ES;Wigler, M
通讯作者：
Wigler, M
影响因子：
3.7
作者：
Aarts, M;Dannenberg, H;de Krijger, RR
通讯作者：
de Krijger, RR
影响因子：
5.4
作者：
Daub, H;Blencke, S;Cotten, M
通讯作者：
Cotten, M