# Genomic and environmental drivers of HCC in Non-Hispanic Blacks: Nature and nurture

> **NIH NIH U01** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2024 · $325,920

## Abstract

Genomicand environmental drivers of HCC in Non-Hispanic Blacks: Nature and nurture:
Non-Hispanic Black Americans (Blacks) develop hepatocellular carcinoma (HCC) at about twice the rate of
Whites and have far higher mortality. HCC has an atypical presentation in Blacks, with lower cirrhosis stage at
the time of HCC diagnosis and more advanced and aggressive HCC. Blacks have higher exposure to
environmental pollutants than Whites and these exposures are associated with liver damage. Although heavy
metals and toxins are known to cause liver injury and cancer, they are often overlooked. This project addresses
the need to understand the genomic and environmental factors causing the atypical presentation of HCC in
Blacks so that effective prevention and treatment strategies can be implemented. It is responsive to RFA-CA-
23-023 in the topic area: Liver cancer in underserved minority populations. This innovative collaboration between
experts in the Liver Cirrhosis Network and liver cancer researchers is expected to yield actionable mechanistic
insights into environmental exposures, tumor immunophenotype, and genetic factors driving the atypical
presentation of HCC in Blacks and may identify new targets for intervention and prevention. The study will also
yield a polygenic risk score for cirrhosis for use among ancestrally diverse populations. The results will alert
patients and providers to the fact that HCC risk is disproportionate to cirrhosis stage in Blacks, raising awareness
of the threat and encouraging early enrollment in surveillance. This project will expand HCC tumor sequencing
and transcriptomic data from Black patients over 4-fold. The Cancer Genome Atlas (TCGA) has only 17 HCCs
from Blacks.
Aim I: Hypothesis: Mutational signatures of toxic damage are more prevalent in HCCs of Blacks than in HCCs
of Whites. We will perform whole exome sequencing on paired HCC/non-HCC specimens from Blacks and use
our in-house pipeline to identify somatic single nucleotide variants (SNVs), to find known and novel mutational
signatures, to define the tumor mutational burden, and to identify mutated genes.
Aim II: Hypothesis: The HCC tumor cells and surrounding microenvironment in Blacks are primed for pro-tumor
activity. We will perform global transcriptomic analysis on paired HCC/non-HCC specimens of Blacks to identify
oncogenic drivers and computationally immunophenotype the microenvironment. Multiplexed IHC will be used
to map the molecular findings onto the histological architecture of the patient's human liver specimens.
Aim III: Hypothesis: Blacks with HCC have a lower prevalence of cirrhosis risk variants than Whites with HCC,
but they have a high prevalence of cancer risk variants, including rare penetrant variants. We will compare the
prevalence of cancer predisposition variants in Blacks with HCC vs. healthy controls, develop
score
cirrhosis
a polygenic risk
for cirrhosis, compare cirrhosis risk between Blacks and Whites with HCC, and explore genetic...

## Key facts

- **NIH application ID:** 10933003
- **Project number:** 5U01CA288425-02
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** Andrea D. Branch
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $325,920
- **Award type:** 5
- **Project period:** 2023-09-21 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10933003

## Citation

> US National Institutes of Health, RePORTER application 10933003, Genomic and environmental drivers of HCC in Non-Hispanic Blacks: Nature and nurture (5U01CA288425-02). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10933003. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*