Systems analysis of the prostate transcriptome in African-American men compared with European-American men.

AIM: African-Americans (AA) have increased prostate cancer risk and a greater mortality rate than European-Americans (EA). AA exhibit a high prevalence of vitamin D deficiency. We examined the global prostate transcriptome in AA and EA, and the effect of vitamin D3 supplementation. PATIENTS & METHODS: Twenty-seven male subjects (ten AA and 17 EA), slated to undergo prostatectomy were enrolled in the study. Fourteen subjects received vitamin D3 (4000 IU daily) and 13 subjects received placebo for 2 months prior to surgery. RESULTS: AA show higher expression of genes associated with immune response and inflammation. CONCLUSION: Systems level analyses support the concept that Inflammatory processes may contribute to disease progression in AA. These transcripts can be modulated by a short course of vitamin D3 supplementation.

Vitamin D3 supplementation, low-risk prostate cancer, and health disparities.

Vitamin D promotes the differentiation of prostate cancer cells, raising the possibility that vitamin D deficiency over time may contribute to the progression from subclinical prostate cancer to clinical disease. Since low-risk prostate cancers are monitored over time in an effort to determine which progress into clinically important, more aggressive cancers, they provide an excellent model in which to study, over an extended period of time, the effects of enhancing vitamin D status and related changes in tumor progression. This is particularly relevant to African-American men, who exhibit a high prevalence of vitamin D deficiency as well as higher incidence of prostate cancer and higher mortality rates from prostate cancer than Caucasians. Our research team has recently completed an open-label clinical trial aimed at assessing the safety and potential efficacy of vitamin D3 supplementation at 4000 international units (IU) per day for one year in subjects diagnosed with early stage, low-risk prostate cancer. The results of this clinical study suggest that supplementation with vitamin D3 at 4000IU per day may benefit patients with early stage, low-risk prostate cancer on active surveillance, because of the improved outcome (a decreased number of positive cores at repeat biopsy) in more than half of the subjects enrolled in the trial. We also observed that, after one year of supplementation, there was no difference in circulating levels of vitamin D between African-American and Caucasian subjects who completed the study. These clinical results also suggest that robust and sustained vitamin D3 supplementation can reduce prostate cancer-related health disparities in African-American men and that these health disparities are at least in part the result of widespread hypovitaminosis D within the African-American population. This article is part of a Special Issue entitled 'Vitamin D Workshop'.

Vitamin D3 supplementation at 4000 international units per day for one year results in a decrease of positive cores at repeat biopsy in subjects with low-risk prostate cancer under active surveillance.

CONTEXT: We wanted to investigate vitamin D in low-risk prostate cancer. OBJECTIVES: The objective of the study was to determine whether vitamin D(3) supplementation at 4000 IU/d for 1 yr is safe and would result in a decrease in serum levels of prostate-specific antigen (PSA) or in the rate of progression. DESIGN: In this open-label clinical trial (Investigational New Drug 77,839), subjects were followed up until repeat biopsy. SETTING: All subjects were enrolled through the Medical University of South Carolina and the Ralph H. Johnson Veterans Affairs Medical Center, both in Charleston, SC. PATIENTS AND OTHER PARTICIPANTS: All subjects had a diagnosis of low-risk prostate cancer. Fifty-two subjects were enrolled in the study, 48 completed 1 yr of supplementation, and 44 could be analyzed for both safety and efficacy objectives. INTERVENTION: The intervention included vitamin D(3) soft gels (4000 IU). MAIN OUTCOME MEASURES: Adverse events were monitored throughout the study. PSA serum levels were measured at entry and every 2 months for 1 yr. Biopsy procedures were performed before enrollment (for eligibility) and after 1 yr of supplementation. RESULTS: No adverse events associated with vitamin D(3) supplementation were observed. No significant changes in PSA levels were observed. However, 24 of 44 subjects (55%) showed a decrease in the number of positive cores or decrease in Gleason score; five subjects (11%) showed no change; 15 subjects (34%) showed an increase in the number of positive cores or Gleason score. CONCLUSION: Patients with low-risk prostate cancer under active surveillance may benefit from vitamin D(3) supplementation at 4000 IU/d.