# The ODC A allele as a driver and therapeutic target of aggressive prostate cancer in African American men

> **NIH NIH R21** · H. LEE MOFFITT CANCER CTR & RES INST · 2022 · $196,934

## Abstract

Project Summary
 The rates of prostate cancer (PCa) incidence and mortality are much higher in African American men (AAM)
versus European American men (EAM), and genetic variations between these races play a critical role. Our
studies have shown that expression of genes that direct polyamine biosynthesis are significantly elevated in
AAM versus EAM PCa, suggesting this pathway may play important roles in driving this cancer health
disparity.
 Ornithine decarboxylase (ODC) is the first and rate-limiting enzyme of polyamine biosynthesis. Notably, the
ODC gene has a single nucleotide polymorphism (SNP) at base +316 in which adenine (A) is substituted for
guanine (G), and this SNP augments ODC promoter activity. Importantly, the ODC A allele is more common in
AAM than EAM, suggesting prostate tumors in AAM having an ODC A allele will have increased ODC levels
and that this drives aggressive prostate tumor biology. Furthermore, difluoromethylornithine (DFMO), a
selective ODC inhibitor, is a highly effective chemoprevention agent in high-risk men harboring at least one
ODC A allele, suggesting the ODC A allele will predict AAM PCa patients that benefit from DFMO treatment.
 These data support our hypothesis that the ODC A allele is both a driver of aggressive prostate tumor
biology and a targetable vulnerability in African American men. To test this hypothesis, in Aim 1 we will
use an allelic discrimination assay to test ~3,800 DNA samples (~1,520 AAM: ~2,280 EAM) from PCa cases
and controls for the presence of the ODC A allele to: (i) establish its frequency in both races; and (ii) assess if
the ODC A allele connotes worse patient outcomes. In Aim 2, we will generate three sets of isogenic PCa cell
lines by CRISPR-based prime editing, where we will test if PCa cells with an ODC A allele have increased
levels of ODC and polyamines and have more aggressive biological phenotypes compared to isogenic PCa
cells with ODC G alleles. In Aim 3, we will test if treatment of our isogenic cells with DFMO and a polyamine
transport inhibitor (polyamine blockage therapy) has differential effects on the phenotypes of PCa cells having
ODC A versus ODC G alleles. Finally, we will also test if there are differential effects of polyamine blocking
therapy on primary PCa tissue explants from AAM having an ODC A allele versus AAM with only ODC G
alleles.
 We submit the proposed studies will benefit African American PCa patients by establishing the ODC A
allele as a prognostic biomarker that will be useful for doctors to assess patient risk, and as a predictive
biomarker that forecasts the success of DFMO as a chemotherapeutic treatment.

## Key facts

- **NIH application ID:** 10356251
- **Project number:** 1R21CA253343-01A1
- **Recipient organization:** H. LEE MOFFITT CANCER CTR & RES INST
- **Principal Investigator:** Jong Y. Park
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $196,934
- **Award type:** 1
- **Project period:** 2022-02-02 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10356251

## Citation

> US National Institutes of Health, RePORTER application 10356251, The ODC A allele as a driver and therapeutic target of aggressive prostate cancer in African American men (1R21CA253343-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10356251. Licensed CC0.

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