非同源末端连接修复通路基因遗传变异与肝细胞癌易感性及其机制研究

Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. Chronic infection with hepatitis B (HBV) is the main risk factor for HCC. Integration of the HBV genome, the process of double-strand breaks (DSBs) and non-homologous end-joining (NHEJ) repairs in both host genome and circular HBV-DNA, is usually considered as an irreversible in the progression to HCC. Host genetic variations that influence the NHEJ repair pathway may determine the outcome of HBV infection. Thus, it is crucial to investigate genetic risk factors which closely related with NHEJ repair. In this study, we aim to evaluate the associations between genetic variants in NHEJ repair genes and risk of HCC. We further explore the potential mechanism of those variants with significant associations by expression analysis and functional studies. The findings of this study will be helpful for determining HCC-related genetic factors, interpreting their molecular mechanisms in HCC development, and screening high-risk population for HCC.

肝癌是威胁全球及我国居民生命和健康的重大疾病。其中慢性乙型肝炎病毒（HBV）感染是HCC发生最为重要的危险因素，HBV DNA整合入肝细胞基因组被认为是乙肝相关性HCC发生发展过程中的重要步骤。HBV整合的实质是双链DNA的断裂并与宿主DNA发生双链断裂修复的过程。其中非同源末端连接(NHEJ)修复是导致双链断裂出现错误修复和DNA整合的重要机制。非同源末端连接修复通路相关基因的遗传差异可能与HBV整合几率及肝细胞癌发病相关。本课题通过病例-对照研究设计，探讨非同源末端连接修复通路相关基因遗传变异与肝细胞癌易感性的关系，对于阳性关联位点进行表达分析和功能研究。本研究有助于对肝细胞癌实施更为有效的危险度评价和个体预防，对今后肝细胞癌的早期诊断和治疗等均具有重要的意义。

肝癌是威胁全球及我国居民生命和健康的重大疾病。其中慢性乙型肝炎病毒（HBV）感染是HCC发生最为重要的危险因素，HBV DNA整合入肝细胞基因组被认为是乙肝相关性HCC发生发展过程中的重要步骤。HBV整合的实质是双链DNA的断裂并与宿主DNA发生双链断裂修复的过程。其中非同源末端连接(NHEJ)修复是导致双链断裂出现错误修复和DNA整合的重要机制。非同源末端连接修复通路相关基因的遗传差异可能与HBV整合几率及肝细胞癌发病相关。本课题通过病例-对照研究设计，探讨非同源末端连接修复通路相关基因遗传变异与肝细胞癌易感性的关系。结果发现rs2267437、rs1051677、rs6941及rs3814175多态性与中国汉族人群肝细胞肝癌易感性有关。本研究有助于对肝细胞癌实施更为有效的危险度评价和个体预防，对今后肝细胞癌的早期诊断和治疗等均具有重要的意义。