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Southern Liver Health Cohort

南方肝脏健康队列

基本信息

批准号：
10905062
负责人：
Cathrine Hoyo
金额：
$ 249万
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 2027-08-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10905062
关键词：
Address Adult Adverse effects Affect African American population Age Air Alcohol consumption Animals Arsenic Biological Specimen Banks Body Burden Cadmium Cancer Etiology Carcinogens Case/Control Studies Cessation of life Chemicals Chronic Cirrhosis Classification Communities DNA Methylation Data Data Collection Disparity Dose Environment Environmental Exposure Environmental Pollutants 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 Care Primary Malignant Neoplasm of Liver Primary carcinoma of the liver cells Probability Protocols documentation Reporting Research Resources Risk Risk Factors Role Rural Rural Minority Sampling Source Susceptibility Gene 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 exposed human population fatty liver disease follow-up human data insight male mouse model non-alcoholic non-alcoholic fatty liver disease nonalcoholic steatohepatitis participant enrollment pollutant programs progression risk 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.

项目总结/文摘