The prostate cancer androgen receptor cistrome in African American men associates with upregulation of lipid metabolism and immune response.

African American (AA) men are more likely to be diagnosed with and die from prostate cancer (PCa) than European American (EA) men. Despite the central role of the androgen receptor (AR) transcription factor in PCa, little is known about the contribution of epigenetics to observed racial disparities. We performed AR ChIP-seq on primary prostate tumors from AA and EA men, finding that sites with greater AR binding intensity in AA relative to EA PCa are enriched for lipid metabolism and immune response genes. Integration with transcriptomic and metabolomic data demonstrated coinciding upregulation of lipid metabolism gene expression and increased lipid levels in AA PCa. In a metastatic prostate cancer cohort, upregulated lipid metabolism associated with poor prognosis. These findings offer the first insights into ancestry-specific differences in the PCa AR cistrome. The data suggest a model whereby increased androgen signaling may contribute to higher levels of lipid metabolism, immune response, and cytokine signaling in AA prostate tumors. Given the association of upregulated lipogenesis with PCa progression, our study provides a plausible biological explanation for the higher incidence and aggressiveness of PCa observed in AA men.

Cancer research. 2022 Jun 22 [Epub ahead of print]

Jacob E Berchuck, Elio Adib, Sarah Abou Alaiwi, Amit K Dash, Jin Na Shin, Dallin Lowder, Collin McColl, Patricia Castro, Ryan Carelli, Elisa Benedetti, Jenny Deng, Matthew Robertson, Sylvan C Baca, Connor Bell, Heather M McClure, Talal El Zarif, Matthew P Davidsohn, Gitanjali Lakshminarayanan, Kinza Rizwan, Darlene G Skapura, Sandra L Grimm, Christel M Davis, Erik A Ehli, Kaitlin M Kelleher, Ji-Heui Seo, Nicholas Mitsiades, Cristian Coarfa, Mark M Pomerantz, Massimo Loda, Michael Ittmann, Matthew L Freedman, Salma Kaochar

Dana-Farber Cancer Institute, Boston, MA, United States., Brigham and Women's Hospital, Boston, United States., Brigham and Women's Hospital, Boston, MA, United States., Baylor College of Medicine, Houston, Texas, United States., Baylor College of Medicine, Houston, TX, United States., Baylor College of Medicine, United States., Baylor College of Medicine, Houston, United States., Weill Cornell Medicine, New York, New York, United States., Weill Cornell Medicine, New York, United States., Hungarian Academy of Sciences, Boston, United States., Dana-Farber Cancer Institute, Brookline, United States., Dana-Farber Cancer Institute, Brookline, MA, United States., One Baylor Plaza, Houston, TX, United States., Avera McKennan Hospital & University Health Center, Sioux Falls, SD, United States., Avera McKenn Hospital & University Health System, Sioux Falls, SD, United States., Dana-Farber Cancer Institute, BOSTON, Massachusetts, United States., Dana-Farber Cancer Institute, Boston, United States., Weill Cornell Medicine, New York, NY, United States., Baylor College of Medicine and Michael E. DeBakey Veterans Association Medical Center, Houston, TX, United States.

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