# Men of African Ancestry are primed for aggressive prostate cancer by high prostate androgens driven by vitamin D deficiency and megalin

> **NIH NIH R01** · UNIVERSITY OF ILLINOIS AT CHICAGO · 2024 · $366,242

## Abstract

SUMMARY
African American (AA) men have twice the risk of aggressive lethal prostate cancer (PCa) and are diagnosed
younger than white men. Epidemiologic studies demonstrate an increased risk of aggressive PCa with vitamin
D deficiency. AA men tend to be deficient in vitamin D because melanin absorbs UV radiation, reducing sunlight-
induced cutaneous vitamin D synthesis. Mounting evidence from my lab demonstrates that vitamin D deficiency
alters the hormone levels of the prostate, which may contribute to the disparity of PCa observed in AA men. Our
recent publications and preliminary data show that vitamin D status regulates prostate dihydrotestosterone
levels, which connects these two disparities and provides a mechanism by which vitamin D affects PCa
aggressiveness. We further implicate megalin as mediating the effect of vitamin D on prostate androgens.
Our long-term goal is to thoroughly examine the relationship between vitamin D and androgen hormones
systemically and how that may vary by ancestry. Here, we propose to examine megalin as a critical protein
involved in prostate hormone regulation. The project includes three complementary, yet independent aims and
the approach combines analysis of patient-derived models and mouse studies with clinical samples from AA and
white men for megalin. This proposal aims to test the hypothesis that vitamin D deficiency leads to increased
prostatic androgens in African American men via megalin, resulting in an increased risk of aggressive PCa.
In contrast to serum levels, there is a paucity of information regarding regulation of intra-tissue levels of
hormones. Given that megalin regulates prostate T levels AND that megalin is regulated by vitamin D, further
understanding this mechanism will provide crucial new insight into the consequences of vitamin D deficiency
which may underpin PCa disparities in African American men. New insight that directly links vitamin D status to
prostate androgens has the potential to move the needle for general practitioners who would then take vitamin
D deficiency seriously for African American patients. Our findings may lead to increased screening for and
treatment of vitamin D deficiency, ultimately decreasing the burden of aggressive and lethal PCa in African
American men.

## Key facts

- **NIH application ID:** 10903496
- **Project number:** 1R01CA290811-01
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT CHICAGO
- **Principal Investigator:** LARISA NONN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $366,242
- **Award type:** 1
- **Project period:** 2024-05-08 → 2029-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10903496

## Citation

> US National Institutes of Health, RePORTER application 10903496, Men of African Ancestry are primed for aggressive prostate cancer by high prostate androgens driven by vitamin D deficiency and megalin (1R01CA290811-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10903496. Licensed CC0.

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