Southern Liver Health Cohort

南方肝脏健康队列

• 批准号: 10336820
• 负责人: Cathrine Hoyo
• 金额: $ 113.84万
• 依托单位: NORTH CAROLINA STATE UNIVERSITY RALEIGH
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-21 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10336820
• 关键词: Address; Adult; Adverse effects; Affect; African American; Age; Air; Alcohol consumption; Animals; Arsenic; Biological Specimen Banks; Body Burden; Cadmium; Cancer Etiology; Carcinogens; Case-Control Studies; Cessation of life; Chemicals; Chronic; Cirrhosis; Communities; DNA Methylation; Data; Data Collection; Dose; Enrollment; Environment; Environmental Exposure; Environmental Pollutants; Environmental Pollution; Epigenetic Process; Ethnic Origin; Excretory function; Exposure to; Fatty Liver; Federally Qualified Health Center; Female; Fibrosis; Food Packaging; General Population; Geography; Health; Health system; Hepatology; Hispanic Americans; House Dust; Human; Incidence; Industrialization; International Agency for Research on Cancer; Knowledge; Link; Liquid substance; Liver; Liver Cirrhosis; Liver Fibrosis; Liver diseases; Longitudinal cohort study; Malignant Neoplasms; Malignant neoplasm of liver; Mass Spectrum Analysis; Measures; Mediating; Metals; Molecular; Mycotoxins; National Health and Nutrition Examination Survey; Nested Case-Control Study; North Carolina; Not Hispanic or Latino; Obesity; Outcome; Participant; Phase; Poison; Poly-fluoroalkyl substances; Population Heterogeneity; Prevalence; Primary Health Care; Primary Malignant Neoplasm of Liver; Primary carcinoma of the liver cells; Protocols documentation; Reporting; Research; Resources; Risk; Risk Factors; Role; Rural; Rural Minority; Sampling; Source; Testing; Textiles; Time; United States; Universities; Variant; Viral hepatitis; Water; aged; alcohol exposure; bioaccumulation; cancer diagnosis; cancer risk; case control; cohort; community clinic; data modeling; data repository; design; disease registry; environmental chemical; ethnic diversity; ethnic minority population; exposed human population; follow-up; human data; insight; male; mouse model; non-alcoholic; non-alcoholic fatty liver disease; nonalcoholic steatohepatitis; pollutant; programs; recruit; response; rural dwellers; sex; toxic metal

PROJECT SUMMARY/ABSTRACT Primary liver cancer, the vast majority of which is hepatocellular carcinoma (HCC) is one of the few cancers with increasing incidence in the US. Incidence of HCC has tripled since 1980, which is particularly worrisome given that HCC confers a median survival of less than two years. The steepest increases in incidence are in Southern rural states and among ethnic minorities. While the prevalence of HCC had paralleled high rates of viral hepatitis in the last several decades, recent increases in the prevalence of nonalcoholic fatty liver disease (NAFLD) and its progression to nonalcoholic steatohepatitis (NASH) with fibrosis and cirrhosis, has fueled HCC in recent years. Yet, these factors alone do not explain the substantial regional and ethnic variation in HCC progression. One understudied but potentially potent HCC risk factor with increasing prevalence that disproportionately affects ethnic minorities, is exposure to environmental contaminants. These contaminants degrade slowly and therefore persist in the environment, providing a stable exogenous source for human exposure. Toxic metal(oid)s such as cadmium and arsenic are classified as probable carcinogens, and emerging data from murine models suggest that exposure is associated with hepatic steatosis, cirrhosis and liver cancer. Per- and poly-fluoroalkyl substances (PFAS) exposure in humans is associated with obesity and NASH. Further, emerging evidence indicates that these environmental exposures can induce epigenetic alterations that may promote adverse effects on the liver, but we lack longitudinal human data. These data underscore the need for longitudinal human data to assess whether and how these contaminants impact HCC risk. To address these knowledge gaps, and in response to RFA-CA-20-049, we propose the Southern Liver Health Study, a longitudinal cohort study of two sub-cohorts comprising 16,000 males and females aged 40 years and older in two Southeastern states, North Carolina and Georgia. We will test the overarching hypothesis that cadmium alone or in a mixture with other toxic metals and PFAS increases the risk of progression from NAFLD to liver fibrosis and HCC. The cohort will be recruited from community clinics including Federally Qualified Health Centers and University Health Systems’ Primary Care Centers and Hepatology programs at Duke, UNC Chapel Hill and Emory. Sub-cohort I will comprise 10,000 otherwise healthy adults who will be followed for 1–5 years, anticipating that ~800 fibrosis cases, including cirrhosis, will develop, and sub-cohort II will comprise 6,000 advanced fibrosis cases, anticipating ~750 HCC cases will develop. We will nest case-control studies within the cohorts, evaluate associations between environmental exposures and HCC incidence, and identify epigenetic marks responsive to contaminants that predict progression to HCC. Impact: This will be the first large-scale effort to longitudinally determine the link between environmental contaminants, liver disease and cancer in a residentially and ethnically diverse population. Additionally, we will create a data and specimen repository that will provide the research community with an invaluable resource to study HCC and other cancers.

项目摘要/摘要 原发性肝癌，其中绝大多数是肝细胞癌（HCC）是为数不多的癌症之一 在美国的事件增加。自1980年以来，HCC的发病率增加了两倍，这尤其令人担忧 HCC承认中位数不到两年。发病率的钢龙车增加在南部 农村国家和少数民族。虽然HCC的患病率与高病毒肝炎的高率平行 在过去的几十年中，非酒精性脂肪肝病（NAFLD）和 近年来，它伴有纤维化和肝硬化的非酒精性脂肪性肝炎（NASH）助长了HCC。 然而，仅这些因素并不能解释HCC进展的大量区域和种族变化。一 研究的但潜在潜在的HCC风险因素，患病率不成比例地影响 少数民族是暴露于环境污染物的。这些污染物缓慢降解，因此 坚持在环境中，为人类暴露提供了稳定的外源性来源。有毒金属（OID） 镉和砷被归类为可能的致癌物，来自鼠模型的新兴数据表明 这种暴露与肝脂肪变性，肝硬化和肝癌有关。每个和多氟烷基 人类中的物质（PFA）暴露与肥胖和NASH有关。此外，新兴的证据 表明这些环境暴露会引起表观遗传改变，这可能会促进不利 对肝脏的影响，但我们缺乏纵向人类数据。这些数据强调了对纵向人类的需求 数据以评估这些污染物是否以及如何影响HCC风险。解决这些知识差距，并 为了响应RFA-CA-20-049 在两个东南部州，北部两个州及其40岁以上的男性和女性的亚霍尔特人，北部 卡罗来纳州和佐治亚州。我们将检验一个总体假设，即单独或与其他混合物中的镉 有毒金属和PFA会增加从NAFLD到肝纤维化和HCC的进展风险。队列将 可以从包括联邦合格的卫生中心和大学卫生系统在内的社区诊所招募 Duke，UNC Chapel Hill和Emory的初级保健中心和肝病学计划。我将完成 10,000名其他健康的成年人将被关注1 - 5年，预计约800例纤维化病例， 包括肝硬化在内，会发展，亚果II将包括6,000例晚期纤维化病例，预计约750例 HCC病例将发展。我们将在队列中嵌套案例对照研究，评估关联 环境暴露和HCC事件，并确定对污染物响应的表观遗传标记 预测向HCC的发展。影响：这将是纵向确定链接的第一个大规模努力 在环境污染物，肝病和癌症之间 人口。此外，我们将创建一个数据和标本存储库，以提供研究社区 有一个宝贵的资源来研究HCC和其他癌症。