title: 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 proteinLRP2and 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.affiliation: Department of Pathology, University of Illinois at Chicago (UIC), Chicago, Illinois, USA.
authors.forename: Zachary
authors.initials: Z
authors.lastname: Richards
authors.affiliation: Division of Urology, Department of Surgery, University of Arizona College of Medicine, Tucson, Arizona, USA.
authors.forename: Ken
authors.initials: K
authors.lastname: Batai
authors.affiliation: Department of Pathology, University of Illinois at Chicago (UIC), Chicago, Illinois, USA.
authors.forename: Rachael
authors.initials: R
authors.lastname: Farhat
authors.affiliation: Division of Urology, Department of Surgery, University of Arizona College of Medicine, Tucson, Arizona, USA.
authors.forename: Ebony
authors.initials: E
authors.lastname: Shah
authors.affiliation: Heartland Assays LLC, Ames, Iowa, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Makowski
authors.affiliation: Department of Pathology, University of Illinois at Chicago (UIC), Chicago, Illinois, USA.
authors.forename: Peter H
authors.initials: PH
authors.lastname: Gann
authors.affiliation: Division of Urology, Department of Surgery, University of Arizona College of Medicine, Tucson, Arizona, USA.
authors.forename: Rick
authors.initials: R
authors.lastname: Kittles
authors.affiliation: Department of Pathology, University of Illinois at Chicago (UIC), Chicago, Illinois, USA.|University of Illinois Cancer Center, Chicago, Illinois, USA.
authors.forename: Larisa
authors.initials: L
authors.lastname: Nonn
mesh_terms: D000354:Africa, Western; D001741:Black or African American / Q000235:genetics*; D000368:Aged; D002117:Calcitriol / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D026561:Low Density Lipoprotein Receptor-Related Protein-2 / Q000235:genetics; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011467:Prostate / Q000378:metabolism* / Q000601:surgery; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000208:ethnology / Q000235:genetics / Q000378:metabolism* / Q000601:surgery; D018167:Receptors, Calcitriol / Q000235:genetics; D053719:Tandem Mass Spectrometry; D059467:Transcriptome; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000378:metabolism; D014808:Vitamin D Deficiency / Q000378:metabolism*; D044465:White People / Q000235:genetics
chemical_list: C000597357:LRP2 protein, human; D026561:Low Density Lipoprotein Receptor-Related Protein-2; D018167:Receptors, Calcitriol; C579457:VDR protein, human; D014807:Vitamin D; C104450:25-hydroxyvitamin D; D002117:Calcitriol