Genetic Epidemiology of Hepatocellular Carcinoma in African Americans

非裔美国人肝细胞癌的遗传流行病学

• 批准号: 10734530
• 负责人: Aaron Peter Thrift
• 金额: $ 36.6万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-26 至 2028-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10734530
• 关键词: Affect; African American; African American population; African ancestry; Alleles; American; Architecture; Asian ancestry; Attention; Biological Specimen Banks; Cancer Etiology; Cancer Patient; Case/Control Studies; Categories; Cessation of life; Cirrhosis; Clinical; Data; Development; Disease; Disparity; Early Diagnosis; Environmental Risk Factor; Epidemiology; Ethnic Origin; Etiology; European; Evaluation; Genetic; Genetic Markers; Genetic Predisposition to Disease; Genetic Risk; Genetic Variation; Genetic study; Genotype; Germ-Line Mutation; Goals; Incidence; Individual; Infrastructure; Intervention; Investigation; Knowledge; Machine Learning; Malignant Neoplasms; Modeling; Molecular; Not Hispanic or Latino; Nucleotides; Pathway interactions; Patients; Pattern; Phase; Policies; Population; Predisposition; Prevalence; Prevention; Primary carcinoma of the liver cells; Race; Relative Risks; Research; Research Personnel; Resources; Risk; Risk Factors; Role; Survival Rate; Texas; Underserved Population; Validation; Variant; alpha-Fetoproteins; blood-based biomarker; cancer site; clinical application; cohort; comparison group; cost efficient; design; ethnic difference; ethnic disparity; follow-up; genetic epidemiology; genetic information; genetic risk factor; genetic variant; genome wide association study; genome-wide; high risk; high risk population; insight; liver cancer model; next generation sequencing; non-genetic; novel; polygenic risk score; prospective; racial difference; racial disparity; risk prediction; risk prediction model; risk stratification; risk variant; screening

Project Summary/Abstract Over the past three decades, hepatocellular carcinoma (HCC) emerged as the fastest growing cancer in the U.S. With cure being possible in less than 10% of patients and 5 year survival rates less than 20%, attention to HCC prevention is paramount. Large racial/ethnic disparities exist in the incidence of HCC in the U.S. where the incidence rates are now 2-fold higher in African Americans than non-Hispanic whites. Differences in prevalence of established HCC risk factors do not fully explain the disproportionately high HCC burden in African Americans, and clinical interventions and policies to close these racial gaps have been largely ineffective because fundamental questions about how this disparity arises remain unanswered. We hypothesize that host genetic factors may predict HCC risk in African Americans and may contribute to the racial disparities in HCC incidence. Genome-wide association studies (GWAS) in European and Asian descent populations have been successful in revealing common genetic risk alleles for HCC. However, germline genetics of HCC varies by the underlying disease etiology and by genetic ancestry. To date, no HCC GWAS has been performed in African Americans. A barrier to genetic studies of HCC in African Americans is the lack of comprehensive genetic, epidemiological and environmental risk factor data from a large cohort of cases. We propose a GWAS of HCC in African Americans using a proven state-wide (Texas) cancer patient contact study approach. In a case-control study, we will investigate the relationship between common genetic variation genome-wide and the risk of HCC in African Americans (Aim 1); these data will provide first insights into the germline genetics of HCC in an African ancestry population. We will use independent GWAS data to validate our top hits and to perform cross-race comparisons to assess the transferability of genetic findings across populations. It is plausible that host genetic factors may also confer susceptibility to HCC risk among patients with cirrhosis, the precursor for HCC. Therefore, in Aim 2, we will identify genetic risk factors for cirrhosis progression to HCC using two parallel case-control studies: comparing cirrhosis patients with controls, and comparing HCC cases with cirrhosis patients. If variants associate with HCC in the HCC versus control comparison (Aim 1) but not the cirrhosis versus control comparison (Aim 2), we may also identify genetic risk factors associated with HCC in the absence of cirrhosis, a potentially growing sub-population of HCC cases. Because early detection of HCC is critical, our last aim (Aim 3) will use information on genetic and non-genetic risk factors to derive clinically applicable comprehensive prediction models for risk stratification. This will be the largest study to date of HCC and cirrhosis in African Americans. Our comprehensive evaluation of novel genetic markers underlying HCC risk in an unmatched cohort of African Americans with HCC will have major translational implications for HCC prevention and early detection.