Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Alterations in the Epigenetic Machinery Associated With Prostate Cancer Health Disparities

Version 1 : Received: 24 May 2023 / Approved: 26 May 2023 / Online: 26 May 2023 (07:24:27 CEST)

A peer-reviewed article of this Preprint also exists.

Craddock, J.; Jiang, J.; Patrick, S.M.; Mutambirwa, S.B.A.; Stricker, P.D.; Bornman, M.S.R.; Jaratlerdsiri, W.; Hayes, V.M. Alterations in the Epigenetic Machinery Associated with Prostate Cancer Health Disparities. Cancers 2023, 15, 3462. Craddock, J.; Jiang, J.; Patrick, S.M.; Mutambirwa, S.B.A.; Stricker, P.D.; Bornman, M.S.R.; Jaratlerdsiri, W.; Hayes, V.M. Alterations in the Epigenetic Machinery Associated with Prostate Cancer Health Disparities. Cancers 2023, 15, 3462.

Abstract

Prostate cancer is driven by acquired genetic alterations, including those impacting the epigenetic machinery. With African ancestry a significant risk factor for aggressive disease, we hypothesize that dysregulation among the roughly 656 epigenetic genes may contribute to prostate cancer health disparities. Interrogating prostate tumor genomic data from 109 men of southern African and 56 men of European Australian ancestry, we found African-derived tumors to present with a longer tail of epigenetic driver gene candidates (72 versus 10). Biased towards African-specific drivers (63 versus 9 shared), many are novel to prostate cancer (18/63) including several putative therapeutic targets (CHD7, DPF3, POLR1B, SETD1B, UBTF and VPS72). Through clustering of all variant types and copy number alterations, we describe two epigenetic PCa taxonomies capable of differentiating patients by ancestry and predicted clinical outcomes. We identified top genes in African and European-derived tumors that represent a multifunctional “generic machinery”, alteration to which may be instrumental in epigenetic dysregulation and prostate tumorigenesis. In conclusion, numerous somatic alterations in the epigenetic machinery drive prostate carcinogenesis but African-derived tumors appear to achieve this with greater diversity amongst such alterations. The greater novelty observed in African-derived tumors illustrates the significant clinical benefit to be derived from a much needed African tailored approach to prostate cancer healthcare aimed at reducing prostate cancer health disparities.

Keywords

prostate cancer; somatic alteration; epigenomics; epigenetic machinery; African ancestry; southern Africa; health disparity

Subject

Medicine and Pharmacology, Urology and Nephrology

Comments (0)

We encourage comments and feedback from a broad range of readers. See criteria for comments and our Diversity statement.

Leave a public comment
Send a private comment to the author(s)
* All users must log in before leaving a comment
Views 0
Downloads 0
Comments 0
Metrics 0


×
Alerts
Notify me about updates to this article or when a peer-reviewed version is published.
We use cookies on our website to ensure you get the best experience.
Read more about our cookies here.