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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).

SUBMITTER: Richards Z

PROVIDER: S-EPMC5256134 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature

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Prostatic compensation of the vitamin D axis in African American men.

Richards Zachary Z Batai Ken K Farhat Rachael R Shah Ebony E Makowski Andrew A Gann Peter H PH Kittles Rick R Nonn Larisa L

JCI insight 20170126 2

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 radi ...[more]

PMID: 28138564

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Project description:The incidence and mortality rates of prostate cancer are significantly higher in African-American men when compared to European-American men. We tested the hypothesis that differences in tumor biology contribute to this survival health disparity. Using microarray technology, we obtained gene expression profiles of primary prostate tumors resected from 33 African-American and 36 European-American patients. These tumors were matched on clinical parameters. We also evaluated 18 non-tumor prostate tissues from 7 African-American and 11 European-American patients. The resulting datasets were analyzed for expression differences on the gene and pathway level comparing African-American with European-American patients. Our analysis revealed a significant number of genes, e.g., 162 transcripts at a false-discovery rate less than 5%, to be differently expressed between African-American and European-American patients. Using a disease association analysis, we identified a common relationship of these transcripts with autoimmunity and inflammation. These findings were corroborated on the pathway level with numerous differently expressed genes clustering in immune response, stress response, cytokine signaling, and chemotaxis pathways. Furthermore, a two-gene tumor signature was identified that accurately differentiated between African-American and European-American patients. This finding was confirmed in a blinded analysis of a second sample set. In conclusion, the gene expression profiles of prostate tumors indicate prominent differences in tumor immunobiology between African-American and European-American men. The profiles portray the existence of a distinct tumor microenvironment in these two patient groups. Experiment Overall Design: A total of 69 fresh-frozen prostate tumors were obtained from the NCI Cooperative Prostate Cancer Tissue Resource (CPCTR) and the Department of Pathology at the University of Maryland (UMD). All tumors were resected adenocarcinomas that had not received any therapy prior to prostatectomy. The macro-dissected CPCTR tumor specimens (n = 59) were reviewed by a CPCTR-associated pathologist, who confirmed the presence of tumor in the specimens. These tissues were collected between 2002 and 2004 at four different sites, with each site providing tissues from both African-American and European-American patients. Information on race/ethnicity (33 African-Americans and 36 European-Americans) was either extracted from medical records (CPCTR) or obtained through an epidemiological questionnaire in which race/ethnicity was self-reported (UMD). Only one patient, a European-American, was also Hispanic. Surrounding non-tumor prostate tissue was collected from 18 of the recruited patients in this study. Of those, 7 were African-American men and 11 were European-American men. We also isolated total RNA from 10 needle biopsy specimens collected from patients at the National Naval Medical Center (one African-American and 9 European-Americans) that did not have prostate cancer. From those, we prepared two RNA pools, each representing 5 patients. Clinicopathological characteristics of the patients, including age at prostatectomy, histology, Gleason score, pathological stage, PSA at diagnosis, tumor size, extraprostatic extension, margin involvement, and seminal vesicle invasion were obtained from CPCTR. For UMD cases, this information was extracted from the medical and pathology records, if available. Written informed consent was obtained from all donors. Tissue collection and study design were approved by the institutional review boards of the participating institutions.

Project description:African American men (AA) carry unequal burdens of several conditions including cancer, diabetes, hypertension, and HIV. Engagement of diverse populations including AA men in research and health promotion practice is vital to examining the health disparities that continue to plague many racially and ethnically diverse communities. To date, there is little research on best practices that indicate locations, community areas and settings to engage AA men in research and health promotion. Traditionally, the AA church has been a key area to engage AA men and women. However, changing tides in attendance of AA parishioners require additional information to identify areas where AAs, particularly, AA men congregate. The AA barbershop has been identified as a place of social cohesion, cultural immersion and solidarity for AA men but specific sub-populations of AA men may be underrepresented. To further investigate additional locales where AA men congregate, this study engaged AA barbers and clients in several urban community barbershops in Chicago, Illinois. 127 AA men over age 18y/o receiving grooming services in 25 Chicago area barbershops across 14 predominantly AA communities were consented and recruited for a quantitative survey study. The self-administered surveys were completed in ~15 min and $10 compensation was provided to men. Descriptive statistics were reported for demographic variables and for frequency of responses for locations to find AA men of specific age ranges for health promotion and screening activities. Outside of the traditionally used churches or barbershops, the top recommended recruitment sites by age were: 18-29y/o- city park or a recreational center; 30-39y/o- gym, bars or the street; 40-49y/o- various stores, especially home improvement stores, and the mall; and 50y/o+- fast food restaurants in the mornings, such as McDonalds, and individual's homes. The study participants also reported that locations where AA men congregate vary by age. Findings from this study illustrate that AA barbers and barbershops remain a key stakeholder in health promotion among AA men. The findings also demonstrate the need for additional research to examine best practices for identifying locations where diverse groups of AA men that vary by age and sexual orientation may congregate in order to support increased health promotion among AA men.

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Prostatic compensation of the vitamin D axis in African American men.

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Prostatic compensation of the vitamin D axis in African American men.

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