Biologic Basis of Disparity in Liver Cancer Survival Among Asian Americans

描述（由申请人提供）：肝细胞癌（HCC）是癌症健康差异的一个明显例子，与非西班牙裔白人相比，亚裔美国人的HCC发病率和死亡率不成比例地高。乙型肝炎病毒（HBV）感染是亚裔美国人HCC的主要危险因素。在早期发现并积极治疗的患者中，HCC生存率显著提高，但在晚期和快速进展的疾病患者中，生存率仍然较低。因此，阐明hbv介导的HCC行为的生物学机制将有助于改善监测、治疗、控制和预防。我们的长期目标是了解hbv相关差异的流行病学原因、社会文化障碍和生物学机制，并开发可以减轻亚裔美国人社区这些疾病负担的工具。在这项研究中，我们将比较hbv感染的老挝人和苗族人的病毒因子和免疫反应，他们的HCC死亡率在亚洲人中最高，而hbv感染的中国人和越南人的存活率更高。重要的是，与其他亚洲种族相比，老挝人和苗族人也在更年轻的时候被诊断出患有更晚期的疾病，这表明存在HCC生存差异的生物学基础。我们的中心假设是，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HCC发病更早，侵袭性更强，导致HCC存活率的差异。我们建议使用新一代测序技术，1)比较hbv感染的老挝人/苗族人与hbv感染的中国人和越南人中与HCC预后相关的病毒因子，2)通过促炎反应(包括NF？b相关基因和抗炎反应，如调节性T细胞，以及T细胞受体使用和HLA等位基因频率。这项研究的影响将是提高对亚裔美国人HCC生存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HCC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.