ROLE OF HEPATITIS C VIRUS IN HEPATOCELLULAR CARCINOMA

丙型肝炎病毒在肝细胞癌中的作用

• 批准号: 3774941
• 负责人: E TABOR
• 金额: --
• 依托单位: DIVISION OF CANCER EPIDEMIOLOGY AND GENETICS
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3774941
• 关键词: Africa; Japanese American; United States; biochemical evolution; gene mutation; genetic strain; geographic site; hepatitis C virus; hepatocellular carcinoma; human tissue; nucleic acid sequence; polymerase chain reaction; serology /serodiagnosis; virus RNA

It has been suggested that hepatitis C virus (HCV) strain variations could explain differing hepatocellular carcinoma (HCC) prevalences. However, few studies have examined the extent to which such variations occur in patients with HCC. Sera obtained between 1969-1981 from 91 HCC patients from Zambia, 35 from Uganda, and 27 from the United States were screened. A PCR-amplified 163-175 nucleotide segment of the 5'-noncoding region was sequenced by dsDNA cycle sequencing. Eight samples contained HCV-RNA (seven from Zambia; one from Uganda; none from the United States). Compared with the prototype strain HCV-1, at least four patterns of nucleotide variation were found. Variations of 0.5-2.3% were observed in this highly conserved virus gene segment. Some of these could be prevalent strain differences in Africa; three have been reported in >50% of HCV infections in Zaire and South Africa and two in >50% in Egypt. These data suggest HCC is not associated with a unique HCV strain, although critical mutations elsewhere in the HCV genome cannot be excluded. Serum samples collected in the 1970s from 25 HCC patients of Japanese descent from Hawaii and matched controls were tested for antibody to HCV and for the presence of HCV-RNA to determine whether HCV was associated with HCC in these patients as it is in Japan in the current decade. Anti- HCV was not detected in any HCC patients; HCV-RNA was detected in two. Although these results are not conclusive, they suggest that HCC in Hawaii was not highly associated with chronic HCV infection in the 1970s. (This may also have been true of HCC patients in Japan, since the evolution of the high prevalence of HCV-associated HCC in Japan today occurred during the past 25-30 years.)

有研究表明，丙型肝炎病毒(丙型肝炎病毒)株的变异可能 解释不同的肝细胞癌(HCC)发病率。然而， 很少有研究研究这种变异在多大程度上发生在 肝细胞癌患者。1969-1981年91例肝细胞癌患者的血清 来自赞比亚的35人，来自乌干达的35人和来自美国的27人接受了筛查。 扩增出5‘端非编码区163-175个核苷酸片段。 通过dsDNA循环测序进行测序。8份样本中含有丙型肝炎病毒RNA (7个来自赞比亚；1个来自乌干达；没有一个来自美国)。 与丙型肝炎病毒原型株相比，至少有四种模式 发现了核苷酸变异。观测到的偏差为0.5%-2.3% 这个高度保守的病毒基因片段。其中一些可能是 非洲流行的菌株差异；有三个已报告在&gt；50% 扎伊尔和南非的丙型肝炎病毒感染率为50%，埃及有两人感染丙型肝炎病毒。 这些数据表明，肝癌与一种独特的丙型肝炎病毒株无关， 尽管丙型肝炎病毒基因组中其他关键突变不可能是 不包括在内。 20世纪70年代收集的25例日本人肝癌患者的血清样本 来自夏威夷的人和匹配的对照组进行了丙型肝炎病毒抗体检测 而对于丙型肝炎病毒RNA的存在，以确定丙型肝炎病毒是否相关 这些患者中的肝细胞癌与本十年日本的情况一样。反- 所有肝细胞癌患者均未检测到丙型肝炎病毒；2例患者检测到丙型肝炎病毒核糖核酸。 尽管这些结果并不是决定性的，但它们表明夏威夷的肝癌 在20世纪70年代，与慢性丙型肝炎病毒感染的相关性并不高。(这是 日本的肝细胞癌患者可能也是如此，因为 今天日本丙型肝炎相关肝细胞癌的高流行发生在 过去25-30年。)