Racial disparities in prostate cancer occurrence may be partly explained by vitamin D deficiency, according to researchers at the Medical University of South Carolina (MUSC) and the Ralph H. Johnson VA Medical Center, who recently shed light on the mechanisms through which vitamin D deficiency may be associated with prostate cancer risk.
The study, “Systems analysis of the prostate transcriptome in African–American men compared with European–American men,” was published in Pharmacogenomics.
It is well documented that African-American (AA) men have a higher risk of developing and dying from prostate cancer than European American (EA) men. Although the mechanisms underlying the disparities are not fully understood, vitamin D is thought to play an important part. Studies have shown that AA men exhibit a high prevalence of vitamin D deficiency, and that vitamin D can regulate the immune system to prevent prostate cancer initiation and progression. But the biological mechanisms underlying such association have not been uncovered.
To understand the role of vitamin D in prostate cancer, the research team developed a prospective, placebo-controlled study with 27 patients (10 AA and 17 EA patients) who were already planning to undergo prostatectomy (surgery to remove all or part of the prostate). Each were assigned to receive either vitamin D (4,000 IU) or placebo for two months. The team aimed to identify gene expression differences between AA and EA men that could explain the disparities in prostate cancer outcomes and whether vitamin D supplementation could affect those differences.
“A lot of previous work shows that D3 levels are much lower in African-Americans than in European Americans and it’s well established that prostate cells are very sensitive to vitamin D levels,” Dr. Sebastiano Gattoni-Celli, professor of radiation oncology at MUSC, said in a press release. “So this raised the possibility that long-term vitamin D deficiency may contribute to the progression of prostate cancer, especially among African-American men. We began to wonder whether eliminating racial disparities in circulating levels of vitamin D, through supplementation, could help reduce the disparities we see in prostate cancer outcomes.”
The researchers found that 8,238 genetic transcripts were differentially expressed in AA and EA men, as assessed by RNA sequencing. AA patients were also found to have higher expression of transcripts involved in immune responses and inflammation.
“The number of genes expressed differently in AA and EA was a really big surprise–we found differences in over 8,000 genes,” said Gattoni-Celli. “I expected something but not this massive difference and it was not a fluke. When we compared our results with previous studies using a less advanced technology, we saw that they, too, found these differences, but not as many.”
When the team compared prostate biopsies of AA men who received vitamin D supplement with those of AA men receiving placebo, there were 817 genes differentially expressed. However, vitamin D administration did not affect gene expression in EA men, possibly because the men already had optimal levels of vitamin D.
When the investigators compared the 817 genes that changed with vitamin D administration to the 8,238 differentially expressed transcripts between EA and AA men, they found an overlap of 346 genes.
The results suggest that vitamin D supplementation in AA patients can affect many genes that are differentially expressed across racial groups. Although it remains to be investigated whether vitamin D supplements can be used as an early-stage therapeutic option for AA men with prostate cancer, the results set the stage for further studies investigating the role of vitamin D in such settings.
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