Vitamin D and genetic ancestry are associated with apoptosis rates in benign and malignant prostatic epithelium

James Stinson, Cordero McCall, Ryan W. Dobbs, Neil Mistry, Adrian Rosenberg, Oluwarotimi S. Nettey, Pooja Sharma, Michael Dixon, Jamila Sweis, Virgilia Macias, Roohollah Sharifi, Rick A. Kittles, Andre Kajdacsy-Balla, Adam B. Murphy*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Purpose: Vitamin D metabolites may be protective against prostate cancer (PCa). We conducted a cross-sectional analysis to evaluate associations between in vivo vitamin D status, genetic ancestry, and degree of apoptosis using prostatic epithelial terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. Experimental design: Benign and tumor epithelial punch biopsies of participants with clinically localized PCa underwent indirect TUNEL staining. Serum levels of 25 hydroxyvitamin D [25(OH)D] and 1,25 dihydroxyvitamin D were assessed immediately before radical prostatectomy; levels of prostatic 25(OH)D were obtained from the specimen once the prostate was extracted. Ancestry informative markers were used to estimate the percentage of genetic West African, Native American, and European ancestry. Results: One hundred twenty-one newly diagnosed men, age 40–79, were enrolled between 2013 and 2018. Serum 25(OH)D correlated positively with both tumor (ρ = 0.17, p = 0.03), and benign (ρ = 0.16, p = 0.04) prostatic epithelial TUNEL staining. Similarly, prostatic 25(OH)D correlated positively with both tumor (ρ = 0.31, p < 0.001) and benign (ρ = 0.20, p = 0.03) epithelial TUNEL staining. Only Native American ancestry was positively correlated with tumor (ρ = 0.22, p = 0.05) and benign (ρ = 0.27, p = 0.02) TUNEL staining. In multivariate regression models, increasing quartiles of prostatic 25(OH)D (β = 0.25, p = 0.04) and Native American ancestry (β = 0.327, p = 0.004) were independently associated with tumor TUNEL staining. Conclusions: Physiologic serum and prostatic 25(OH)D levels and Native American ancestry are positively associated with the degree of apoptosis in tumor and benign prostatic epithelium in clinically localized PCa. Vitamin D may have secondary chemoprevention benefits in preventing PCa progression in localized disease.

Original languageEnglish (US)
Pages (from-to)352-363
Number of pages12
JournalProstate
Volume83
Issue number4
DOIs
StatePublished - Mar 2023

Keywords

  • apoptosis
  • chemoprevention
  • genetic ancestry
  • prostate cancer
  • vitamin D

ASJC Scopus subject areas

  • Urology
  • Oncology

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