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Genetic and biological drivers of prostate cancer disparities in Black men

Nature Reviews Urology (2023)Cite this article

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Abstract

Black men with prostate cancer have historically had worse outcomes than white men with prostate cancer. The causes of this disparity in outcomes are multi-factorial, but a potential basis is that prostate cancers in Black men are biologically distinct from prostate cancers in white men. Evidence suggests that genetic and ancestral factors, molecular pathways involving androgen and non-androgen receptor signalling, inflammation, epigenetics, the tumour microenvironment and tumour metabolism are contributing factors to the racial disparities observed. Key genetic and molecular pathways linked to prostate cancer risk and aggressiveness have potential clinical relevance. Describing biological drivers of prostate cancer disparities could inform efforts to improve outcomes for Black men with prostate cancer.

Key points

  • Black men have higher rates of prostate cancer and more aggressive disease than white men.

  • Black men have biologically distinct prostate cancers from white men, including genetic alterations, protein differences, tumour microenvironment, and even circulating hormones and vitamins that might contribute to the differing phenotype of prostate cancers from Black men compared with white men.

  • Socioeconomic status has an important role in the disparities in prostate cancer seen in Black men compared with white men, but it does not fully explain the differences.

  • The biological differences between prostate cancers from Black men and white men could provide targets for therapies and precision medicine for Black men that can aid in addressing disparities in treatment outcomes between the two groups.

  • More research focused on Black men to elucidate how these biological differences can be used to develop targeted treatments, including increased clinical trial participation, is needed.

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Fig. 1: Racial differences in environmental risk factors, genetics and therapy access lead to disparity in response.
Fig. 2: Differential drivers of carcinogenesis and therapy sensitivity in Black men with prostate cancer.

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Acknowledgements

This work was supported by grants from the Prostate Cancer Foundation (2022 PCF Young Investigator Award to J.G.), Department of Defense (Health Disparity Research Award W81XWH-19-1-0748 to J.G.), and American Cancer Society (Research Scholar Grant RSG-18-018-01-CPHPS to J.G.).

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Authors and Affiliations

  1. Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA

    Jun Gong, Daniel M. Kim, Michael R. Freeman, Hyung Kim, Leigh Ellis, Bethany Smith, Dan Theodorescu, Edwin Posadas, Robert Figlin, Neil Bhowmick & Stephen J. Freedland

  2. Department of Urology, Cedars-Sinai Medical Center, Los Angeles, CA, USA

    Michael R. Freeman, Hyung Kim, Dan Theodorescu & Stephen J. Freedland

  3. Section of Urology, Durham VA Medical Center, Durham, NC, USA

    Stephen J. Freedland

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Contributions

J.G. and D.M.K. researched data for the article. J.G., D.M.K. and S.J.F. contributed substantially to discussion of the content. All authors wrote the article and reviewed and/or edited the manuscript before submission.

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Correspondence to Jun Gong.

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Competing interests

J.G.: consulting or advisory role — EMD Serono, Elsevier, Exelixis, QED Therapeutics, Natera, Basilea, HalioDx, Eisai, Janssen, Astellas and Amgen. D.T.: consulting or advisory role — Aurora Oncology, Machavert Pharmaceuticals, Merck and Urogen Pharma. E.P.: consulting or advisory role — CytoLumina, Genentech/Roche, Janssen Oncology, Janssen Oncology and Novartis; speakers’ bureau — Bayer; research funding — Pfizer; patents, royalties, other intellectual property — patent on NanoVelcro Assay for circulating tumour cells in prostate cancer; and travel, accommodations, expenses — TRACON Pharma. R.F.: leadership — 4Dx and Apollomics; consulting or advisory role — Bristol-Myers Squibb, CBT Pharmaceuticals and Johnson & Johnson; and research funding — Bristol-Myers Squibb (institution), Calithera Biosciences (institution), Exelixis (institution), Merck (institution) and Peloton Therapeutics (institution). N.B.: leadership — Kairos Pharma Lmt. and Armida Labs, Inc; consulting — TRACON Pharma, Cellgene and Xencor; research funding — Xencor. S.J.F.: consulting or advisory role — Merck, Astellas, AstraZeneca, Pfizer, Janssen, Bayer, Clovis, Sanofi, Myovant and Exact Sciences. All other authors declare no competing interests.

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Gong, J., Kim, D.M., Freeman, M.R. et al. Genetic and biological drivers of prostate cancer disparities in Black men. Nat Rev Urol (2023). https://doi.org/10.1038/s41585-023-00828-w

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