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

Award Number: R01CA290811
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 05/08/2024
PERIOD OF PERFORMANCE END DATE: 04/30/2029

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


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $369,337 )
2025	2025	UNIVERSITY OF ILLINOIS	809 S MARSHFIELD AVE M/C 551	CHICAGO	IL	60612	COOK	USA	Cancer Biology Research	000	2	4/15/2025	NON-COMPETING CONTINUATION	$332,403
2025	2025	UNIVERSITY OF ILLINOIS	809 S MARSHFIELD AVE M/C 551	CHICAGO	IL	60612	COOK	USA	Cancer Biology Research	001	2	5/22/2025	NON-COMPETING CONTINUATION	$36,934
														Subtotal = $369,337

Issue Date FY: 2024 ( Subtotal = $366,242 )
2024	2024	UNIVERSITY OF ILLINOIS	809 S MARSHFIELD AVE M/C 551	CHICAGO	IL	60612	COOK	USA	Cancer Biology Research	000	1	5/8/2024	NEW	$366,242
														Subtotal = $366,242

Grand Total All Awards = $735,579

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

Award Number: R01CA290811

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 05/08/2024

PERIOD OF PERFORMANCE END DATE: 04/30/2029

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