Understanding the Determinants of Racial/Ethnic Disparities in Liver Cancer and Chronic Liver Disease in Understudied and High-Risk Populations

摘要 肝细胞癌(HCC)和慢性肝病(CLD)是 美国对种族/少数民族的影响不成比例。在多种族队列(MEC)研究中，一项长期的- 站在不同种族的未来队列(20万名参与者)上，我们观察到了显著的种族差异 在肝癌发病率中，拉丁裔发病率最高，其次是夏威夷原住民、非裔美国人、 日裔美国人和白人。在美国出生的拉美裔人，特别是男性，患肝癌的几率最高 队列中的发病率。我们还发现，非酒精性脂肪肝(NAFLD)是最常见的原因 在日裔美国人和夏威夷原住民中，NALFD的患病率出人意料地高。这些 研究结果为阐明造成健康差距的因素提供了基础。 这些种群。到目前为止，还没有肝病研究包括日裔美国人和夏威夷原住民； 因此，在了解肝细胞癌和非酒精性肝病之间差异的因素方面仍然存在很大的知识差距。 这些未被充分研究的高危人群。MEC及其全面的生活方式、环境和遗传 数据为阐明造成这些健康差异的决定因素提供了一个独特的机会。在这 我们将研究生活方式、遗传、社会和环境因素与肝细胞癌和非酒精性脂肪肝的关系。 在MEC参与者中，更好地了解高危少数群体的疾病病因和潜在因素 种族差异。我们将利用MEC的现有资源，提供详细的人口统计、生活方式、社区- 来自SEER癌症登记处的水平数据、健康状况数据以及癌症发病率和死亡率信息 以及州和国家死亡率数据库，以及一个大型血样生物储存库。这些数据有 在所有MEC参与者中以一致的方式收集，以便进行有效的种族比较。我们的 具体目标是1)量化已知风险因素(慢性丙型肝炎和乙型肝炎、肥胖、 代谢综合征、饮酒和吸烟)与肝癌发病率的种族差异 其他危险因素(生活方式和社会/背景因素)解释了肝细胞癌剩余的种族差异 2)评估特定种族的生活方式， 社会和背景因素以及遗传因素与五个民族和地区的NAFLD相关 量化他们对NALFD风险的种族/民族差异的贡献。在这项研究完成后，我们会 增进对某些民族最重要的风险因素和潜在差异因素的了解 在肝癌和非酒精性脂肪肝中。确定和界定危险因素对种族/民族差异的贡献 肝癌和非酒精性脂肪肝将是改善这些疾病初级预防战略的最重要因素。

ABSTRACT Hepatocellular carcinoma (HCC) and chronic liver diseases (CLD) and are significant health problems in the United States affecting racial/ethnic minorities disproportionately. In the Multiethnic Cohort (MEC) Study, a long- standing ethnically diverse prospective cohort (>200,000 participants), we observed striking ethnic differences in HCC incidence with Latinos having the highest incidence followed by Native Hawaiians, African Americans, Japanese Americans, and whites. US-born Latinos, particularly men, experience the highest rates of HCC incidence in the cohort. We also found nonalcoholic fatty liver disease (NAFLD) to be the most common cause of CLD and an unexpectedly high NALFD prevalence in Japanese Americans and Native Hawaiians. These findings provide the groundwork for studies to elucidate the factors that account for health disparities across these populations. To date, no liver disease studies have included Japanese Americans and Native Hawaiians; thus, a large knowledge gap remains in understanding the factors underlying disparities in HCC and NALFD in these understudied high-risk populations. The MEC with its comprehensive lifestyle, environmental, and genetic data offers a unique opportunity to elucidate the determinants that account for these health disparities. In this study we will examine the association of lifestyle, genetic, social, and contextual factors with HCC and NAFLD among MEC participants to better understand disease etiology in high-risk minorities and the factors underlying ethnic disparities. We will use existing resources of the MEC with detailed demographic, lifestyle, neighborhood- level data, health condition data, and cancer incidence and mortality information from SEER Cancer registries and state and national mortality databases, as well as a large biorepository of blood samples. These data have been collected in a consistent fashion amongst all MEC participants to permit valid ethnic comparisons. Our specific aims are 1) To quantify the contribution of known risk factors (chronic hepatitis C and B, adiposity, metabolic syndrome, alcohol intake and tobacco smoking) to ethnic differences in HCC incidence and identify additional risk factors (lifestyle and social/contextual factors) explaining the remaining ethnic variation in HCC incidence which would suggest novel or ethnic-specific mechanisms; 2) To evaluate ethnic-specific lifestyle, social and contextual factors and genetic factors that are associated with NAFLD across five ethnic groups and quantify their contributions to racial/ethnic differences in NALFD risk. Upon completion of this study, we will improve understanding of risk factors most important in certain ethnic groups and factors underlying disparities in HCC and NAFLD. The identification and defining the contribution of risk factors to racial/ethnic differences in HCC and NAFLD will be paramount for improving strategies for primary prevention of these diseases.