Abstract A079: Genetic ancestry and vitamin D may predict degree of prostatic apoptosis in prostate tumor and benign epithelium among men undergoing radical prostatectomy

Abstract

Abstract There is evidence that vitamin D metabolites such as 25 hydroxyvitamin D [25(OH)D], may be protective against prostate cancer (PCa). Vitamin D and its analogs are hypothesized to have pro-apoptotic effects in multiple cell lines. Blacks have higher rates of vitamin D deficiency, higher tumor progression rates 1,2, and higher apoptosis rates3 compared to Whites. West African ancestry (WAA) may confound this relationship if it is associated with both vitamin D status and apoptosis rates. Our objective is to assess for independent associations between in vivo vitamin D status, genetic ancestry, and degree of apoptosis using prostatic epithelial Terminal deoxynucleotide transferase dUTP Nick End Labeling (TUNEL) staining. Radical prostatectomy specimens of men with clinically localized PCa were stained for TUNEL. Prostatic and serum levels of 25(OH)D and serum levels of 1,25 hydroxyvitamin D were assessed at the time of surgery. Ancestry informative markers were used to estimate the percentage of genetic West African, Native American, and European ancestry. Continuous variables were compared using medians tests across three groups of vitamin D status. Categorical variables were compared using the Chi-Squared test. Correlations between the degree of TUNEL staining and vitamin D metabolites were assessed using Spearman correlations. Linear regressions were used to access the bivariant associations between tumor and benign epithelial TUNEL staining with quartiles of ancestry, and serum and prostatic vitamin D metabolite levels. Multivariate linear regressions for the percentage of benign and tumor TUNEL staining were used to test the independent associations of vitamin D metabolites and genetic ancestry. Overall, 121 men, age 40-79, who underwent radical prostatectomy were enrolled between 2013-2018. 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) prostatic tissue TUNEL staining. Relative to West African ancestry, Native American ancestry was more strongly 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 significant predictors of tumor TUNEL staining. Physiologic levels of serum and prostatic 25(OH)D and percentage of Native American ancestry are positively associated with the degree of apoptosis in tumor and benign prostatic epithelium from men with clinically localized PCa. Vitamin D may have secondary chemoprevention benefits in preventing PCa progression in localized disease. Citation Format: Cordero L. McCall, James Stinson, Ryan W. Dobbs, Neil Mistry, Adrian Rosenberg, Oluwarotimi Nettey, Pooja Sharma, Michael Dixon, Jamila Sweis, Virgilia Macias, Roohollah Sharifi, Rick A. Kittles, Andre Kajdacsy Balla, Adam B. Murphy. Genetic ancestry and vitamin D may predict degree of prostatic apoptosis in prostate tumor and benign epithelium among men undergoing radical prostatectomy [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr A079.