PreS2 Mutant of Hepatitis B Virus as Early Marker of Hepatocellular Carcinoma

描述(申请人提供)：乙肝病毒(乙肝病毒)是严重肝病的主要原因，包括慢性肝炎，肝硬变和肝细胞癌(肝细胞癌)在世界各地和美国，特别是在少数族裔，如非裔美国人，印第安人和亚裔美国人。最近的临床数据表明，肝细胞癌和乙肝病毒变异与表面基因前S2区域的框内缺失有关。我们假设前S2突变的乙肝病毒基因组在乙肝病毒相关的癌变中起着因果作用，因此这些突变在患者中的出现可以作为肝细胞癌风险的早期标志。我们将通过确认preS2突变与肝癌之间的流行病学联系来检验这一假说，并确定这些突变的存在是否可以用作慢性乙肝患者发生肝癌风险增加的标志。预计这些实验将提供直接证据，证明preS2突变可能用作慢性乙型肝炎肝细胞癌风险的标志，并在未来引导确定预防和/或治疗肝癌的分子靶点。乙肝病毒是世界上痛苦和死亡的主要原因，它会导致肝脏损伤、肝硬变(肝疤痕形成)，最重要的是导致肝癌。目前对肝癌的治疗是不够的，这在很大程度上是因为我们无法及早发现癌症。我们希望我们的研究能够为这些患者的肝癌早期发现和治疗开辟新的途径。

DESCRIPTION (provided by applicant): Hepatitis B virus (HBV) is a major cause of serious liver diseases, including chronic hepatitis, cirrhosis and hepatocellular carcinoma (HCC) throughout the world and the US, especially among minorities such as African Americans, Native Americans, and Asian Americans. Recent clinical data have pointed to an association between HCC and HBV mutants with in-frame deletions in the preS2 region of the surface gene. We hypothesize that preS2 mutant HBV genomes play a causal role in HBV-associated carcinogenesis, and hence the appearance of these mutants in patients can be used as an early marker for risk of HCC. We will test this hypothesis, by confirming an epidemiological link between preS2 mutants and HCC, and determining if the presence of these mutants can be used as a marker for increased risk of HCC development in patients with chronic hepatitis B. It is anticipated that these experiments will provide direct evidence on the possible utility of preS2 mutants as a marker of HCC risk in chronic hepatitis B, as well as lead in the future to the identification of molecular targets for the prevention and/or therapy of HCC. Hepatitis B virus is a major cause of suffering and death in the world, by causing liver injury, cirrhosis (liver scarring) and, most importantly, liver cancer. Current treatment for liver cancer is inadequate, to a large extent because of our inability to detect the cancer early enough. We hope that our research can lead to the development of new ways for the early detection and hence treatment of liver cancer in these patients.