Southern Liver Health Cohort

南方肝脏健康队列

基本信息

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
项目类别：
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

项目摘要

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.

项目概要/摘要原发性肝癌，其中绝大多数是肝细胞癌（HCC），是少数几种癌症之一自 1980 年以来，美国 HCC 的发病率增加了两倍，这一点尤其令人担忧。肝癌的中位生存期不足两年，发病率增幅最大的是南部地区。农村地区和少数民族中 HCC 的患病率与病毒性肝炎的高发病率相似。近几十年来，非酒精性脂肪性肝病 (NAFLD) 的患病率有所增加，近年来，其进展为伴有纤维化和肝硬化的非酒精性脂肪性肝炎（NASH），加剧了肝癌的发生。然而，仅这些因素并不能解释 HCC 进展的巨大地区和种族差异。未被充分研究但潜在有效的 HCC 危险因素，其患病率不断增加，影响不成比例少数族裔暴露于环境污染物中，因此这些污染物降解缓慢。持续存在于环境中，为人类接触有毒金属（类化合物）提供稳定的外源。镉和砷被列为可能的致癌物，来自小鼠模型的新数据表明该暴露与肝脂肪变性、肝硬化和肝癌有关。此外，越来越多的证据表明，人类接触 PFAS 物质与肥胖和 NASH 相关。表明这些环境暴露可以诱导表观遗传改变，从而可能促进不良反应对肝脏的影响，但我们缺乏纵向人体数据，这些数据强调了纵向人体数据的必要性。评估这些污染物是否以及如何影响 HCC 风险的数据，以弥补这些知识差距。为了回应 RFA-CA-20-049，我们提出了南方肝脏健康研究，这是一项针对两项研究的纵向队列研究子队列由 16,000 名年龄在 40 岁及以上的男性和女性组成，分布于东南部两个州、北卡罗莱纳州和乔治亚州将测试单独的镉或与其他物质的混合物的总体假设。有毒金属和 PFAS 会增加 NAFLD 进展为肝纤维化和 HCC 的风险。从社区诊所招募，包括联邦合格的健康中心和大学健康系统杜克大学、北卡罗来纳大学教堂山分校和埃默里大学的初级保健中心和肝病学项目将包括在内。 10,000 名原本健康的成年人将被跟踪 1-5 年，预计约有 800 例纤维化病例，包括肝硬化，将会发展，第二亚队列将包括 6,000 例晚期纤维化病例，预计约 750 例我们将在队列中进行病例对照研究，评估之间的关联。环境暴露和 HCC 发病率，并识别对污染物有反应的表观遗传标记预测进展为 HCC 的影响：这将是纵向确定这种联系的第一个大规模努力。在居住和种族多样化的环境污染物、肝病和癌症之间此外，我们将创建一个数据和样本存储库，为研究界提供服务。拥有研究 HCC 和其他癌症的宝贵资源。