Host and Viral Genetic Variation in HBV-Related Hepatocellular Carcinoma.
Host and Viral Genetic Variation in HBV-Related Hepatocellular Carcinoma.
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DOI：
10.3389/fgene.2018.00261
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发表时间：
2018
影响因子：
3.7
通讯作者：
Winkler CA
中科院分区：
文献类型：
--
作者：
An P;Xu J;Yu Y;Winkler CA
肝细胞癌（HCC）是男性第五大常见癌症，也是全球癌症死亡的第二大原因。HCC的高患病率部分是由于慢性HBV感染的高患病率，而高死亡率是由于缺乏早期检测的生物标志物和晚期HCC的治疗选择有限。观察到的HCC发展的个体差异可归因于HBV基因型和突变的差异，宿主易感的种系遗传变异，肿瘤特异性体细胞突变的获得以及环境因素。HBV基因型C和preS、基本核心启动子（BCP）或HBx区域的突变与HCC风险增加相关。全基因组关联研究已经确定了KIF1B、HLA-DQ、STAT4和GRIK1的共同多态性与hbv相关HCC的风险改变。HBV整合到生长控制基因（如TERT）、促癌基因或抑癌基因中，以及截断的HBx的致癌活性促进了肝癌的发生。TERT启动子和经典癌症信号通路的体细胞突变，包括Wnt （CTNNB1）、细胞周期调节（TP53）和表观遗传修饰（ARID2和MLL4）在肝脏肿瘤组织中经常被检测到。识别与肿瘤发生和进展相关的HBV和宿主变异对改善早期诊断和预后具有临床价值；而识别驱动肿瘤发生的体细胞突变有望为HCC患者的精确治疗提供信息。
Hepatocellular carcinoma (HCC) is the fifth most common cancer in men and the second leading cause of cancer deaths globally. The high prevalence of HCC is due in part to the high prevalence of chronic HBV infection and the high mortality rate is due to the lack of biomarkers for early detection and limited treatment options for late stage HCC. The observed individual variance in development of HCC is attributable to differences in HBV genotype and mutations, host predisposing germline genetic variations, the acquisition of tumor-specific somatic mutations, as well as environmental factors. HBV genotype C and mutations in the preS, basic core promoter (BCP) or HBx regions are associated with an increased risk of HCC. Genome-wide association studies have identified common polymorphisms in KIF1B, HLA-DQ, STAT4, and GRIK1 with altered risk of HBV-related HCC. HBV integration into growth control genes (such as TERT), pro-oncogenic genes, or tumor suppressor genes and the oncogenic activity of truncated HBx promote hepatocarcinogenesis. Somatic mutations in the TERT promoter and classic cancer signaling pathways, including Wnt (CTNNB1), cell cycle regulation (TP53), and epigenetic modification (ARID2 and MLL4) are frequently detected in hepatic tumor tissues. The identification of HBV and host variation associated with tumor initiation and progression has clinical utility for improving early diagnosis and prognosis; whereas the identification of somatic mutations driving tumorigenesis hold promise to inform precision treatment for HCC patients.