# The Impact of Genetic Ancestry on Racial Disparities in Hepatocellular Carcinoma Risk and Mortality

> **NIH NIH K08** · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · 2023 · $237,065

## Abstract

PROJECT SUMMARY
Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death in the United States and worldwide.
There are significant racial disparities in HCC risk. Blacks, Hispanics and Asians all have increased risk of HCC
compared to non-Hispanic Whites. Also, Blacks consistently have the lowest survival after HCC diagnosis. Likely,
genetic variation and gene-environment interactions modify HCC risk and may also contribute to racial
differences in HCC survival. The objective of this proposal is to leverage our established cohort of diverse
patients with chronic liver disease, cirrhosis and HCC to identify how genetic variation, including genetic
ancestry, drives disparities in HCC risk and mortality, in the context of known risk factors and social determinants
of health. This career development award will provide Dr. Patricia Jones, a skilled hepatologist with experience
in clinical epidemiology, with the opportunity to gain additional training in genetic epidemiology, genetic analysis,
longitudinal data analysis and predictive modeling. Understanding how genetic ancestry drives HCC risk
and outcomes is the first step towards identifying specific ancestry-associated genes and pathways that
are linked to increased risk and/or poor survival. In Aim 1, we will define the relationship between genetic
ancestry and HCC risk by genotyping 200 participants with HCC, 400 participants with chronic liver disease ±
cirrhosis and 400 healthy controls from the NIH All of Us study. We will define how HCC risk differs based on
genetic ancestry across the genome (global) and at specific chromosomal locations for commonly mutated genes
in HCC, e.g. TERT, ARID1A, RB, CTNNB1, TP53, PNPLA3, and IDH1/2. We will also explore new genetic
targets as they emerge from ongoing genetic studies. We will build and validate an HCC risk-prediction model
that incorporates genetic ancestry. By integrating genetic and clinical data with individual social factors and social
determinants of health, the proposed project will improve our ability to accurately predict HCC risk. By
distinguishing patients at highest risk, our risk stratification tool could transform the current HCC screening
paradigm. In Aim 2, we will use genotype data from 200 participants with HCC to develop a survival prediction
model that incorporates genetic ancestry, social determinants and clinical data. We will validate the final survival
model in two separate cohorts of HCC patients. The knowledge gained from our comprehensive survival analysis
in Aim 2 will improve our understanding of the genetic determinants of survival disparities and could lead to more
precise estimates of prognosis, a key patient-centered outcome. The formal and experiential training received
through coursework, internships and workshops will enable Dr. Jones to develop an ancestry-informed HCC risk
prediction model that will form the basis of a future R01 application. With guidance from a strong multidisciplinary
mentor...

## Key facts

- **NIH application ID:** 10705026
- **Project number:** 5K08CA255413-02
- **Recipient organization:** UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
- **Principal Investigator:** Patricia Denise Jones
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $237,065
- **Award type:** 5
- **Project period:** 2022-09-15 → 2027-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10705026

## Citation

> US National Institutes of Health, RePORTER application 10705026, The Impact of Genetic Ancestry on Racial Disparities in Hepatocellular Carcinoma Risk and Mortality (5K08CA255413-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10705026. Licensed CC0.

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