Prostatic compensation of the vitamin D axis in African American men
Zachary Richards, Ken Batai, Rachael Farhat, Ebony Shah, Andrew Makowski, Peter H. Gann, Rick Kittles, Larisa Nonn
Zachary Richards, Ken Batai, Rachael Farhat, Ebony Shah, Andrew Makowski, Peter H. Gann, Rick Kittles, Larisa Nonn
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Clinical Research and Public Health Endocrinology Oncology

Prostatic compensation of the vitamin D axis in African American men

Abstract

BACKGROUND. African American (AA) men are disproportionately affected by both prostate cancer (PCa) and vitamin D deficiency compared with European American (EA) men. Vitamin D deficiency is linked to increased PCa aggressiveness and mortality. Therefore, it has been hypothesized that vitamin D deficiency may contribute to the PCa disparity between AA and EA men.

METHODS. We studied a cross sectional group of 60 PCa patients (AA, n = 31; EA, n = 29) who underwent radical prostatectomy. Vitamin D metabolites 25-hydroxyvitamin D (25(OH)D) and 1,25-dihydroxyvitamin D (1,25(OH)2D) were measured in the serum and tissue by uHPLC-MS-MS. Tissue was laser capture microdissected, and gene expression was quantified by microarray. DNA isolated from whole blood was genotyped for West African ancestry markers and vitamin D–related SNPs.

RESULTS. Serum concentrations of 25(OH)D were lower in AAs, but concentrations of 1,25(OH)2D in the prostate tissue were higher compared with EAs. Expression of the vitamin D receptor was higher in prostate tissue from AAs. Expression of the extracellular receptor of vitamin D binding protein, LRP2, was positively associated with West African ancestry and inversely associated with tissue 25(OH)D concentrations in AAs.

CONCLUSIONS. The relationships between vitamin D binding protein LRP2 and vitamin D metabolites suggest that the prohormone is actively transported into the prostate, followed by intraprostatic conversion to the active hormone, rather than passive diffusion. These findings support the presence of a compensatory response in prostate tissue to vitamin D deficiency in AAs and reveal a previously unknown complexity involving tissue distribution of vitamin D metabolites.

FUNDING. Department of Defense Prostate Cancer Research Program Idea Award for Disparities Research PC121923 (LN and RK) and the NIH 1R01MD007105 (RK).

Authors

Zachary Richards, Ken Batai, Rachael Farhat, Ebony Shah, Andrew Makowski, Peter H. Gann, Rick Kittles, Larisa Nonn

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Figure 2

Radical prostatectomy patients of African ancestry had lower 25-hydroxyvitamin D (25(OH)D) in the serum but higher 1,25-dihydroxyvitamin D (1,25(OH)2D) in the prostate.

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Radical prostatectomy patients of African ancestry had lower 25-hydroxyv...
(A) comparison of serum levels of 25(OH)D (European American [EA], n = 29; African American [AA], n = 30) and 1,25(OH)2D (EA, n = 26; AA, n = 29) measured by uHPLC-MS-MS between radical prostatectomy patients of AA and EA ancestry. (B) Correlation between vitamin D metabolites 25(OH)D and 1,25(OH)2D in the serum by ancestry (EA, n = 26; AA, n = 29). (C) Comparison of prostate tissue (benign area) levels of 25(OH)D (EA, n = 29; AA, n = 30) and 1,25(OH)2D (EA, n = 24; AA, n = 19) measured by uHPLC-MS-MS. (D) Correlation between prostatic levels of 25(OH)D and 1,25(OH)2D (EA, n = 24; AA, n = 19). (E) Serum levels of vitamin D binding protein (DBP) quantified by polyclonal antibody ELISA and correlation with 25(OH)D levels in the (F) serum and (G) prostate tissue (EA, n = 24; AA, n = 19). P <0.1; differences by ancestry were determined by 2-sided Wilcoxon signed-rank test and correlations determined by Spearman’s rank coefficient.