Biologic Basis of Disparity in Liver Cancer Survival Among Asian Americans

描述(申请人提供)：肝细胞癌(HCC)是一个明显的癌症健康差距的例子，因为与非西班牙裔白人相比，亚裔美国人的肝癌发病率和死亡率高得不成比例。在亚裔美国人中，乙肝病毒感染是罹患肝细胞癌的主要危险因素。在癌症被早期发现并积极治疗的患者中，肝癌存活率显著提高，但在晚期和快速进展疾病的患者中，存活率仍然较低。因此，阐明乙肝病毒介导的肝细胞癌行为的生物学机制可能有助于改进监测、治疗、控制和预防。我们的长期目标是了解乙肝病毒相关差异的流行病学原因、社会文化障碍和生物机制，并开发工具来减轻这些疾病对亚裔美国人社区的负担。在这项研究中，我们将比较感染乙肝病毒的老挝人和苗族人的病毒因素和免疫反应，他们的肝癌死亡率在亚洲人中最高，而感染乙肝病毒的中国人和越南人的存活率更高。重要的是，老挝人和苗族人被诊断的年龄也较小，但与其他亚洲种族相比，他们患有更严重的疾病，这表明这种肝细胞癌存活率的差异有生物学基础。我们的中心假设是，在老挝/苗族人群中存在病毒变异和宿主免疫反应的差异，这在一定程度上导致了更早的发病和更具侵袭性的肝癌，从而导致了肝癌存活率的差异。我们建议使用下一代测序技术来1)比较感染乙肝病毒的老挝/苗族人和感染乙肝病毒的中国人和越南人中与肝癌预后相关的病毒因素，以及2)通过包括核因子B相关基因在内的促炎反应和抗炎反应(如调节性T细胞)的基因表达活性，以及T细胞受体的使用和HLA等位基因频率来评估与这些相同组的肝癌存活相关的免疫反应。这项研究的影响将是提高对亚裔美国人之间肝癌存活率差异的生物学基础的理解，并可能导致更好的风险分层和基于宿主和病毒因素的肝癌治疗定制。

DESCRIPTION (provided by applicant): Hepatocellular carcinoma (HCC) is a blatant example of a cancer health disparity in that HCC is disproportionally higher in incidence and mortality among Asian Americans compared with non-Hispanic Whites. Infection by the Hepatitis B virus (HBV) is the principal risk factor for HCC among Asian Americans. HCC survival rates have significantly improved among those whose cancer is detected early and treated aggressively, but remain short among those with advanced, and rapidly progressive disease. Thus elucidating biological mechanisms underlying the behavior of HBV-mediated HCC will potentially contribute to improved surveillance, treatment, control and prevention. Our long term goal is to understand epidemiologic causes, sociocultural barriers, and biologic mechanisms of HBV-related disparities, and to develop tools which can decrease the burden of these diseases on the Asian American community. In this study, we will compare viral factors and immune responses in HBV-infected Laotian and Hmong, who experience the highest HCC mortality rates among Asians, with HBV-infected Chinese and Vietnamese, who experience better survival rates. Importantly, Laotian and Hmong are also diagnosed at a younger age but with more advanced disease compared to other Asian ethnicities suggesting that there is a biologic basis to this disparity in HCC survival. Our central hypothesis is that differences in viral variants and host immune responses exist within the Laotian/Hmong population, which in part cause an earlier onset and more aggressive form of HCC, resulting in a disparity in HCC survival. We propose using next generation sequencing technologies to 1) compare viral factors associated with HCC prognosis in HBV-infected Laotian/Hmong to HBV-infected Chinese and Vietnamese and 2) assess immune responses associated with HCC survival in these same groups by gene expression activity of pro-inflammatory responses including NF?B-related genes and anti-inflammatory responses such as regulatory T cells, as well as T cell receptor usage and HLA allele frequencies. The impact of this study will be to improve the understanding of the biologic basis of disparities in HCC survival among Asian American ethnicities and may lead to better risk stratification and tailoring of treatment of HCC based upon host and viral factors.