# Investigating the mechanisms of aggressive prostate cancer in African American Veterans

> **NIH VA I01** · VETERANS AFFAIRS MED CTR SAN FRANCISCO · 2023 · —

## Abstract

African American (AA) men have the highest incidence and mortality rate from prostate cancer in
the United States. We recently showed that AA men with low-risk prostate cancer have a two-fold
increased risk of death compared to men of other racial groups. While the causes of this stark
disparity are multifactorial, we hypothesize that prostate cancers in AA men harbor unique
genomic alterations that give rise to more aggressive prostate cancer. Towards this end, we have
performed an initial meta-analysis of existing sequencing studies and found candidate driver
genes associated with ancestry. However, the ability to determine the effect of these candidates
on prostate cancer biology is limited due to the lack of biological cell models from different
ancestral backgrounds. In Aim 1, we will find additional molecular alterations associated with
grade using whole genome sequencing of prostate cancer cases from 100 AA veteran men seen
at the San Francisco Veterans Affairs Health Care System. In Aim 2, we will characterize the
transcriptomic states of different prostate epithelial cell populations by performing single-cell RNA-
seq of organoids derived from AA and EA men. In Aim 3, we will develop new prostate cell models
from AA patients using prostate organoids. We will then perturb ancestry-associated driver genes
and determine whether the functional effects of these genes are augmented in different ancestral
backgrounds. At the conclusion of these studies we will have expanded our understanding of the
molecular pathways that are associated with aggressiveness in different ancestral backgrounds.
We will also generate a resource of prostate cell models from AA men for the scientific community
to investigate prostate cancer disparities. This project will generate substantial knowledge of the
mechanisms that underlie prostate cancer disparities that could ultimately lead to improved
treatment of AA men with prostate cancer and the reduction of cancer health disparities.

## Key facts

- **NIH application ID:** 10370188
- **Project number:** 1I01CX002444-01
- **Recipient organization:** VETERANS AFFAIRS MED CTR SAN FRANCISCO
- **Principal Investigator:** Franklin W Huang
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2023
- **Award amount:** —
- **Award type:** 1
- **Project period:** 2022-10-01 → 2026-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10370188

## Citation

> US National Institutes of Health, RePORTER application 10370188, Investigating the mechanisms of aggressive prostate cancer in African American Veterans (1I01CX002444-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10370188. Licensed CC0.

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