# Project 1: Molecular Predictors of Prostate Cancer Progression and Mortality

> **NIH NIH P50** · FRED HUTCHINSON CANCER CENTER · 2024 · $475,269

## Abstract

PROJECT SUMMARY
Prostate cancer (PC) remains a leading cause of cancer-related morbidity and mortality and represents one of
the largest health disparities in the US, with men of African ancestry having the highest incidence and mortality
rates. Additional risk factors for PC include older age, family history of PC, and germline genetics. We previously
reported that rare germline variants in DNA repair genes (gDRG) are enriched in men with lethal/metastatic PC.
We have also developed a novel multi-ancestry polygenic risk score (PRSm) that is highly predictive of PC risk
across diverse populations and associated with a younger age at PC diagnosis and conversion from active
surveillance to treatment. The combined impact of gDRG and PRS on PC progression is not well understood,
particularly in multi-ancestry patients. In this Project, we will use a population-based approach to identify and
recruit diverse, non-European, multi-ancestry PC patients, examine the interplay between rare variants in gDRG
(e.g., BRCA2) with PRSm and the association with PC clinical features. To accomplish this, we will also develop
a clinical-grade paired tumor-germline assay, which will additionally enable large-scale examination of gDRG in
combination with high PRSm using tumor molecular profiles. We will also parse out specific, individual variants
that contribute the greatest effect on a high PRSm, Finally, we will conduct a tailored PC screening clinical trial
for individuals at highest risk of PC due to gDRG and determine patterns of interest, enrollment and adherence
to PC screening. Together, we seek to address and mitigate health care disparities related to prostate cancer
genetics, and the factors influencing clinical implementation. Ultimately, we seek a better understanding of the
interplay between rare gDRG variants and PRSm for a combined analysis of germline genetic information to
improve risk prediction and tailored PC screening for men across a broader populations.

## Key facts

- **NIH application ID:** 10919778
- **Project number:** 5P50CA097186-23
- **Recipient organization:** FRED HUTCHINSON CANCER CENTER
- **Principal Investigator:** HEATHER CHENG
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $475,269
- **Award type:** 5
- **Project period:** 2002-09-19 → 2028-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10919778

## Citation

> US National Institutes of Health, RePORTER application 10919778, Project 1: Molecular Predictors of Prostate Cancer Progression and Mortality (5P50CA097186-23). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10919778. Licensed CC0.

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