# Genetic predictors of prostate cancer survival

> **NIH NIH R01** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2022 · $109,052

## Abstract

PROJECT SUMMARY/ABSTRACT
The underlying scientific premise of the parent grant is that the risk factors and mechanisms that drive prostate
cancer development likely differ from those that drive prostate cancer mortality. Here, the proposed supplement
project seeks to understand whether race-specific risk factor associations and mechanisms contribute to long-
standing, poorly understood excess prostate cancer disease burden among Black men. The proposed project
focuses on prostate cancer risk in Black men in this context through examination of a risk factor – vitamin D –
previously found to be associated with an increased risk of prostate cancer incidence, but a decreased risk of
prostate cancer mortality based primarily on data from White men. Although the complex relationship of vitamin
D with prostate cancer has been well-studied in white men, there is limited research focused on elucidating this
relationship among Black men. This is notable given the well-established: 1) higher risk of developing and dying
from prostate cancer for Black compared to White men; 2) Black-White differences in vitamin D profiles defined
by circulating concentrations of 25-hydroxyvitamin D (25(OH)D) – the metabolite used to define vitamin D status
– with chronically low concentrations in Black populations, and Black-White differences in genetic variants in
multiple vitamin D-related genes; and 3) the identification of genetic variants in vitamin D related genes
associated with prostate cancer risk. The persistent gaps in the vitamin D-prostate cancer research focused on
Black men likely perpetuate existing disparities as vitamin D, a modifiable factor, is known to influence several
molecular processes that drive carcinogenesis in the prostate. This knowledge gap highlights the importance of
cancer health disparities research and research translation in reducing the overall cancer burden. Given this, the
proposed project will implement the gene-centered approach used in the parent grant to determine whether and
how genetic variants (single nucleotide polymorphisms (SNPs)) in genes from the vitamin D pathway influence
prostate cancer in an understudied group at high risk for both vitamin D deficiency and prostate cancer.
Specifically, the proposed supplement project examines the role of genes involved in vitamin D synthesis
(CYP27A1 and CYP27B1), transport (GC), activity (VDR and RXR), and metabolism (CYP24A1) in relation to
prostate cancer risk (Aim #1) and mortality (Aim #2). Additionally, both aims will include validation analyses of
the identified SNP associations in an independent sample of Black men (Aims 1b and 2b), and in silico analyses
to identify the functional basis for the identified SNP associations based on normal (Aim 1c) and malignant
prostate tissue (Aim 2c). This proposal is a distinctly valuable career development opportunity for the candidate
as it will provide mentorship and training in cancer genomics and genetic epidemiology, a new area for the...

## Key facts

- **NIH application ID:** 10599501
- **Project number:** 3R01CA244948-02S2
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** ROBERT J. KLEIN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $109,052
- **Award type:** 3
- **Project period:** 2021-01-15 → 2025-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10599501

## Citation

> US National Institutes of Health, RePORTER application 10599501, Genetic predictors of prostate cancer survival (3R01CA244948-02S2). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10599501. Licensed CC0.

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