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

> **NIH NIH P50** · FRED HUTCHINSON CANCER RESEARCH CENTER · 2021 · $188,956

## Abstract

PROJECT SUMMARY/ABSTRACT 
Prostate cancer (PC) is a major cause of cancer-related morbidity and mortality. Prostate-specific antigen (PSA) 
screening is controversial, and current consideration of high-risk men is inadequate. Additionally, 
clinicopathological criteria are insufficient to differentiate indolent versus aggressive disease. The recent 
discovery of a high prevalence of high-to-moderate penetrance germline cancer risk mutations in metastatic PC 
(mPC) will lead to increased genetic testing and cascade testing of unaffected male relatives, thus identifying 
men at high risk for developing aggressive PC. Preliminary evidence suggests the need for refined cancer 
screening in this high-risk group. The overall intent of this project is to find men with germline mutations of 
interest, both those with mPC as well as their male first-degree relatives who are at high risk for aggressive PC. 
We seek to further characterize PC in the context of germline DNA repair gene (gDRG) defects using evaluation 
of clinical, pathologic and molecular features, including targeted next generation sequencing methods; to recruit 
at-risk male first-degree relatives through cascade genetic testing; and to offer a novel PC early detection clinical 
trial incorporating novel biomarkers, including age-adjusted PSA thresholds, imaging, novel urine biomarkers 
and the tumor prognostic biomarkers we discovered and validated in the past grant period, and to further 
understand the crucial process of cascade genetic testing that will be required for optimal outcomes. The 
proposed aims are: 
Specific Aim 1: Determine clinical, pathologic and molecular predictors of gDRG mutation carriers 
 among men with mPC. 
Specific Aim 2: Conduct an early detection study for male gDRG mutation carriers at high risk for mPC. 
Specific Aim 3: Characterize the stepwise cascade genetic testing process from index cases to their at 
 risk first-degree relatives (FDRs). 
This effort builds upon our current population-based SPORE work focused on finding and validating novel 
prognostic biomarkers for aggressive PC (e.g., tumor DNA methylation and mRNA expression biomarkers for 
distinguishing men at high risk for metastatic progression and PC-specific mortality) and transitions towards a 
more direct clinical applicability. We believe our approach will be of high interest and relevance to men with 
mPC and gDRG, and their sons and brothers who may be at increased risk for mPC due to carrying the same 
gDRG mutation. At present, no unified PC early detection recommendations exist for men at increased PC risk 
defined by inherited gDRG mutations. Our PC early detection clinical study will use established and novel 
minimally invasive biomarkers with a goal of changing the standard of care for this high-risk group.

## Key facts

- **NIH application ID:** 10247715
- **Project number:** 5P50CA097186-19
- **Recipient organization:** FRED HUTCHINSON CANCER RESEARCH CENTER
- **Principal Investigator:** JANET L STANFORD
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $188,956
- **Award type:** 5
- **Project period:** 2002-09-19 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10247715

## Citation

> US National Institutes of Health, RePORTER application 10247715, Project 1: Molecular Predictors of Prostate Cancer Progression and Mortality (5P50CA097186-19). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10247715. Licensed CC0.

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