Yang Zongguo, Zhuang Liping, Lu Yunfei, Xu Qingnian, Tang Bozong, Chen Xiaorong
Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
Fudan University Shanghai Cancer Center, Shanghai, China.
Oncotarget. 2016 Mar 15;7(11):12525-36. doi: 10.18632/oncotarget.7123.
Basal core promoter (BCP) A1762T/G1764A dual mutations in hepatocarcinogenesis remain controversial. Published studies up to June 1, 2015 investigating the frequency of A1762T/G1764A dual mutations from chronic hepatitis B virus (HBV) infection, including hepatocellular carcinoma (HCC), were systematically identified. A total of 10,240 patients with chronic HBV infection, including 3729 HCC cases, were included in 52 identified studies. HCC patients had a higher frequency of BCP A1762T/G1764A dual mutations compared with asymptomatic HBsAg carriers (ASC) and patients with chronic hepatitis B (CHB) and liver cirrhosis (LC) (OR = 5.59, P < 0.00001; OR = 2.87, P < 0.00001; OR = 1.55, P = 0.02, respectively). No statistically significant difference was observed in the frequency of A1762T/G1764A dual mutations in cirrhotic HCC versus non-cirrhotic HCC patients (OR = 2.06, P = 0.05). Chronic HBV-infected patients and HCC patients with genotype B had a significantly lower risk of A1762T/G1764A dual mutations compared with patients with genotype C (OR = 0.30, P < 0.0001 and OR = 0.34, P = 0.04, respectively). In HBV genotype C subjects, A1762T/G1764A dual mutations contributed to significantly higher risk for HCC developing compared with non-mutation ones (OR = 3.47, P < 0.00001). In conclusion, A1762T/G1764A dual mutations increase the risk of HBV-related hepatocellular carcinoma, particularly in an HBV genotype C population, even without progression to cirrhosis.
肝癌发生过程中，基础核心启动子（BCP）A1762T/G1764A双突变仍存在争议。系统检索了截至2015年6月1日发表的研究，这些研究调查了慢性乙型肝炎病毒（HBV）感染（包括肝细胞癌（HCC））中A1762T/G1764A双突变的频率。52项纳入研究共纳入10240例慢性HBV感染患者，其中包括3729例HCC病例。与无症状HBsAg携带者（ASC）、慢性乙型肝炎（CHB）患者和肝硬化（LC）患者相比，HCC患者BCP A1762T/G1764A双突变的频率更高（OR分别为5.59，P<0.00001；OR为2.87，P<0.00001；OR为1.55，P=0.02）。在肝硬化HCC患者与非肝硬化HCC患者中，A1762T/G1764A双突变的频率未观察到统计学显著差异（OR=2.06，P=0.05）。与C基因型患者相比，B基因型慢性HBV感染患者和HCC患者发生A1762T/G1764A双突变的风险显著更低（OR分别为0.30，P<0.0001和OR为0.34，P=0.04）。在HBV C基因型受试者中，与未发生突变者相比，A1762T/G1764A双突变导致HCC发生的风险显著更高（OR=3.47，P<0.00001）。总之，A1762T/G1764A双突变增加了HBV相关肝细胞癌的风险，特别是在HBV C基因型人群中，即使没有进展为肝硬化。
