Yuen Man-Fung, Tanaka Yasuhito, Mizokami Masashi, Yuen John Chi-Hang, Wong Danny Ka-Ho, Yuan He-Jun, Sum Siu-Man, Chan Annie On-On, Wong Benjamin Chun-Yu, Lai Ching-Lung
Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong.
Carcinogenesis. 2004 Sep;25(9):1593-8. doi: 10.1093/carcin/bgh172. Epub 2004 Apr 16.
The role of hepatitis B virus (HBV) genotypes, core promoter (CP) and precore mutants on hepatocellular carcinoma (HCC) is still controversial. We aimed to determine their role on the development and clinical features of HCC. HBV genotypes and CP/precore mutations were determined in 90 HCC patients and 180 matched control patients. In the 90 HCC patients, 22 (24.4%) and 68 (75.6%) had subtype Ba and genotype C, respectively. The prevalence of genotype C and CP mutations was significantly higher in HCC patients compared with controls (75.6 versus 57.8%, P = 0.004; 90.9 versus 74.8%, respectively, P = 0.007). Among carriers of genotype C, 91.8% of the HCC patients and 88.8% of controls had CP mutations. Among carriers of subtype Ba, HCC patients had a higher prevalence of CP mutations compared with controls (88.2 versus 54.5%, respectively, P = 0.02). By logistic regression analysis, the only factor associated with HCC was a mutation of the CP region (P = 0.032). There were no differences in the clinical features on presentation, the chance of receiving treatment and the cumulative survival rate for chemoembolization-treated patients between patients with subtype Ba and genotype C. There was too small a number of CP wild-type to do a similar comparison with CP mutants. In conclusion, there was a significantly higher prevalence of both genotype C and CP mutations in patients with HCC. The association between HBV genotype C and HCC was probably not genuine but was due to the high percentage of CP mutations in patients with genotype C.
乙型肝炎病毒(HBV)基因型、核心启动子(CP)和前核心突变体在肝细胞癌(HCC)中的作用仍存在争议。我们旨在确定它们在HCC发生发展及临床特征中的作用。对90例HCC患者和180例匹配的对照患者进行了HBV基因型及CP/前核心突变检测。在90例HCC患者中,分别有22例(24.4%)和68例(75.6%)为Ba亚型和C基因型。与对照组相比,HCC患者中C基因型和CP突变的发生率显著更高(分别为75.6%对57.8%,P = 0.004;90.9%对74.8%,P = 0.007)。在C基因型携带者中,91.8%的HCC患者和88.8%的对照者存在CP突变。在Ba亚型携带者中,HCC患者CP突变的发生率高于对照者(分别为88.2%对54.5%,P = 0.02)。通过逻辑回归分析,与HCC相关的唯一因素是CP区域突变(P = 0.032)。Ba亚型和C基因型患者在临床表现、接受治疗的机会以及经化疗栓塞治疗患者的累积生存率方面无差异。CP野生型数量过少,无法与CP突变体进行类似比较。总之,HCC患者中C基因型和CP突变的发生率均显著更高。HBV C基因型与HCC之间的关联可能并非真实存在,而是由于C基因型患者中CP突变的比例较高。