Prostate Cancer in African Americans: Study Focuses on Vitamin D Receptor Function and Genomic Ancestry

By: Amanda E. Ruffino, BA
Posted: Monday, June 26, 2023

Moray J. Campbell, PhD, of Cedars-Sinai Medical Center, Los Angeles, and colleagues focused on investigating the genomic actions of the vitamin D receptor (VDR) in prostate cancer in African Americans, which has been associated with vitamin D3 deficiency. Their findings, which identified that genomic ancestry drives the VDR complex composition and is disrupted by BAZ1A (a novel driver for prostate cancer in African Americans), were published in Cancer Research Communications.

The investigators analyzed VDR proteogenomic data from prostate cell lines in African Americans and European Americans and four clinical cohorts. The results showed that nonmalignant prostate cells from African Americans had the highest protein content in the VDR complex. Cells from African Americans also exhibited greater regulation of chromatin accessibility by 1α,25(OH)₂D₃ (active form of vitamin D3), significant enhancer-enriched VDR cistrome (genomic binding sites), and the largest 1α,25(OH)₂D₃-dependent transcriptome compared with cells from European Americans. However, these VDR functions were compromised in prostate cancer cells (RC43T) from African Americans and were significantly distinct from cell models from European Americans.

In addition, the study identified reduced expression of a chromatin remodeler called BAZ1A in prostate cancer cohorts of African Americans and RC43T cells compared with nonmalignant prostate cells (RC43N) from African Americans. Restoring BAZ1A expression increased 1α,25(OH)₂D₃-regulated VDR-dependent gene expression in RC43T cells.

The clinical relevance of VDR cistrome-transcriptome relationships was examined in three different clinical prostate cancer cohorts. Of note, in African American patients with prostate cancer, the genes bound by VDR and/or associated with 1α,25(OH)₂D₃-dependent open chromatin were found to predict disease progression, respond to vitamin D3 supplementation in tumors, and exhibit differential responses to 25(OH)D3 serum levels. Furthermore, correlation analyses revealed that BAZ1A and components of the VDR complex identified by proteogenomic analyses significantly strengthened the correlation between VDR and target gene specifically in prostate cancer in African Americans.

Disclosure: For full disclosures of the study authors, visit aacrjournals.org.

Cancer Research Communications

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