# Germline Determinants of Prostate Cancer Evolution

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2024 · $597,235

## Abstract

Abstract
Prostate cancer is the most commonly diagnosed non-skin cancer in men, and the second most common cause
of cancer death for men. It is a high-incidence, high-fatality, high-morbidity and high-cost cancer that is growing
increasingly frequent in our aging population. Clinically, the majority of prostate cancers present as indolent, and
are unlikely to significantly influence a man’s health over his lifetime. Nevertheless, a significant number of
prostate tumors are diagnosed while localized but have substantial metastatic potential. Once these colonize
distant sites, they become almost uniformly lethal. Current standard of care for clinical risk-stratification involves
serum abundance of prostate specific antigen (PSA), a digital rectal exam and biopsy. While these are beneficial,
~30-40% of men are over- or under-treated. Therefore, a central problem in prostate cancer remains
understanding this dramatic variability in the aggressiveness of localized prostate cancers. We hypothesize
that the clinical and molecular evolution of localized prostate cancers are shaped by germline genomic
features. Strong preliminary data support this idea. Prostate cancer is the most heritable solid cancer. It shows
strong variability across ancestries, and specific genetic features predict both risk of incidence and disease
aggression. We will test our hypothesis with three complementary aims. Aim #1 quantifies germline-somatic
interactions using transcriptome-wide association studies (TWAS) and pathway-somatic interaction analysis.
Aim #2 then identifies ancestry-based germline-somatic interactions. Finally Aim #3 will assess the
generalizability of germline-somatic interactions for clinical risk prediction by developing a targeted DNA-
sequencing panel and evaluating biomarker potential in large patient cohorts. To achieve these aims, we will
leverage publicly available datasets as well as biobanking repositories at UCLA, linked to both established and
novel bioinformatics methods. Together, these aims provide three complementary strategies to quantify how the
specific clinical and molecular evolutionary features of localized prostate cancer are influenced by specific
germline polymorphisms.

## Key facts

- **NIH application ID:** 10817097
- **Project number:** 5R01CA270108-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Paul Christopher Boutros
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $597,235
- **Award type:** 5
- **Project period:** 2023-04-01 → 2028-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10817097

## Citation

> US National Institutes of Health, RePORTER application 10817097, Germline Determinants of Prostate Cancer Evolution (5R01CA270108-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10817097. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*