Volume 83, Issue 4 pp. 352-363
ORIGINAL ARTICLE

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

James Stinson MD

James Stinson MD

Division of Urology, Cook County Health and Hospitals System, Chicago, Illinois, USA

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Cordero McCall MBA, MPH

Cordero McCall MBA, MPH

Department of Urology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA

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Ryan W. Dobbs MD

Ryan W. Dobbs MD

Division of Urology, Cook County Health and Hospitals System, Chicago, Illinois, USA

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Neil Mistry MD

Neil Mistry MD

Department of Urology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA

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Adrian Rosenberg BA

Adrian Rosenberg BA

Department of Urology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA

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Oluwarotimi S. Nettey MD

Oluwarotimi S. Nettey MD

Department of Urology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA

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Pooja Sharma BS, BA, BMS

Pooja Sharma BS, BA, BMS

Department of Urology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA

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Michael Dixon BS

Michael Dixon BS

Department of Urology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA

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Jamila Sweis BS

Jamila Sweis BS

Department of Urology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA

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Virgilia Macias MD

Virgilia Macias MD

Department of Pathology, University of Illinois at Chicago School of Medicine, Chicago, Illinois, USA

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Roohollah Sharifi MD

Roohollah Sharifi MD

Section of Urology, Jesse Brown VA Medical Center, Chicago, Illinois, USA

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Rick A. Kittles PhD

Rick A. Kittles PhD

Department of Population Sciences, Division of Health Equities, City of Hope Cancer Center, Duarte, California, USA

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Andre Kajdacsy-Balla MD, PhD

Andre Kajdacsy-Balla MD, PhD

Department of Pathology, University of Illinois at Chicago School of Medicine, Chicago, Illinois, USA

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Adam B. Murphy MD, MBA, MSCI

Corresponding Author

Adam B. Murphy MD, MBA, MSCI

Division of Urology, Cook County Health and Hospitals System, Chicago, Illinois, USA

Department of Urology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA

Section of Urology, Jesse Brown VA Medical Center, Chicago, Illinois, USA

Correspondence Adam B. Murphy, Department of Urology, Northwestern University Feinberg School of Medicine, 303 E Chicago Ave, Tarry Bldg 16-729, Chicago, IL 60611, USA.

Email: [email protected]

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First published: 07 December 2022

James Stinson and Cordero McCalls contributed equally to this study.

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.

CONFLICT OF INTEREST

The authors declare no conflict of interest.

DATA AVAILABILITY STATEMENT

A deidentified version of the analytic database would be made available as an SPSS or an Excel database for interested parties. Researchers should have a credible research idea and data sharing will be subject to Northwestern University's Data Use agreement.

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