# Project 1: Epigenetic variations associated with aggressiveness in prostate cancer among Puerto Rican men

> **NIH NIH U54** · H. LEE MOFFITT CANCER CTR & RES INST · 2024 · $184,602

## Abstract

ABSTRACT | FULL RESEARCH PROJECT 1
Puerto Rican (PR) Hispanic/Latino (H/L) men have the highest prostate cancer (PCa) mortality among Hispanic
populations. According to the recent PR Cancer Registry data, PCa is the leading cancer type in terms of
incidence (35% of all cancer cases) and mortality (17% of all cancer deaths) in PR H/L men. They have
significantly higher PCa-specific mortality than non-Hispanic white (NHW) and non-Hispanic Black (NHB) men;
addressing this gap constitutes our central efforts. While socioeconomic status and access to healthcare are
contributors, manifest differences in molecular features between racial groups highlight the role of tumor biology
in racially disparate outcomes in PCa. Our long-term goal is to identify DNA methylation biomarkers driving gene
expression changes that underly PCa therapy resistance and aggressiveness in at-risk populations, particularly
PR H/L men. The central hypothesis is that differences in tumor DNA methylation patterns and population
admixture are associated with drug response and aggressiveness in PCa in PR H/L men. The rationale is that
identifying the molecular basis of PCa disparities will serve to reduce the burden of lethal PCa disparities affecting
PR H/L men. Our goals will be accomplished through two Specific Aims: Aim 1) Investigate associations between
aggressiveness and methylated genes in PCa among the PR H/L population and the impact of methylation on
their expression. (1a) Investigate differentially methylated genes associated with drug resistance and
aggressiveness among PR H/L PCa patients and compare with methylation data from NHB from the Florida PCa
biobank, NHW PCa patients from MCC, and TCGA. (1b) Evaluate differential DNA methylation on gene
expression patterns. We will establish comparisons with previous data obtained from NHW men from MCC and
TCGA. (1c) Evaluate whether population admixture will modify the methylation level of PR-specific methylated
genes. Further, we will investigate whether genes that contain ancestry determinants are associated with the
aggressiveness of PCa and disparity. Aim 2. Assess the contribution of DNA methylation to PCa resistance to
standard therapies using drug-resistant PCa sublines and liquid biopsies from PCa patients progressing after
treatment. (2a) Identify differentially methylated genes associated with drug-resistant phenotypes using cell-
based models of drug resistance including castration resistance, enzalutamide resistance, and docetaxel
resistance. (2b) Evaluate the expression of differentially methylated genes in resistant sublines compared to
sensitive cell lines. (2c) Assess the effect of DNA methylation inhibition on drug sensitivity in resistant
phenotypes. (2d) As an exploratory aim, we will evaluate resistance-associated methylation profiles in blood
samples from PR and MCC patients previously treated with androgen deprivation therapy, androgen receptor-
targeting agents, or taxane-based chemotherapy. The ident...

## Key facts

- **NIH application ID:** 10931481
- **Project number:** 5U54CA163068-12
- **Recipient organization:** H. LEE MOFFITT CANCER CTR & RES INST
- **Principal Investigator:** Jong Y. Park
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $184,602
- **Award type:** 5
- **Project period:** 2012-09-24 → 2028-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10931481

## Citation

> US National Institutes of Health, RePORTER application 10931481, Project 1: Epigenetic variations associated with aggressiveness in prostate cancer among Puerto Rican men (5U54CA163068-12). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10931481. Licensed CC0.

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