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Health inequity drives disease biology to create disparities in prostate cancer outcomes
William G. Nelson, … , Tamara L. Lotan, Angelo M. De Marzo
William G. Nelson, … , Tamara L. Lotan, Angelo M. De Marzo
Published February 1, 2022
Citation Information: J Clin Invest. 2022;132(3):e155031. https://doi.org/10.1172/JCI155031.
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Review

Health inequity drives disease biology to create disparities in prostate cancer outcomes

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Abstract

Prostate cancer exerts a greater toll on African American men than on White men of European descent (hereafter referred to as European American men): the disparity in incidence and mortality is greater than that of any other common cancer. The disproportionate impact of prostate cancer on Black men has been attributed to the genetics of African ancestry, to diet and lifestyle risk factors, and to unequal access to quality health care. In this Review, all of these influences are considered in the context of the evolving understanding that chronic or recurrent inflammatory processes drive prostatic carcinogenesis. Studies of inherited susceptibility highlight the contributions of genes involved in prostate cell and tissue repair (BRCA1/2, ATM) and regeneration (HOXB13 and MYC). Social determinants of health appear to accentuate these genetic influences by fueling prostate inflammation and associated cell and genome damage. Molecular characterization of the prostate cancers that arise in Black versus White men further implicates this inflammatory microenvironment in disease behavior. Yet, when Black and White men with similar grade and stage of prostate cancer are treated equally, they exhibit equivalent outcomes. The central role of prostate inflammation in prostate cancer development and progression augments the impact of the social determinants of health on disease pathogenesis. And, when coupled with poorer access to high-quality treatment, these inequities result in a disparate burden of prostate cancer on African American men.

Authors

William G. Nelson, Otis W. Brawley, William B. Isaacs, Elizabeth A. Platz, Srinivasan Yegnasubramanian, Karen S. Sfanos, Tamara L. Lotan, Angelo M. De Marzo

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Figure 2

Pro-carcinogenic prostate microenvironment.

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Pro-carcinogenic prostate microenvironment.
Prostate epithelium is assau...
Prostate epithelium is assaulted by inflammatory ROS and reactive nitrogen species (RNS), by activated dietary carcinogens, and by inflammatory cytokines. The result is cell and genome damage leading to activation of stress response pathways, reduced terminal differentiation, and regenerative proliferation characteristic of the prostate cancer precursor proliferative inflammatory atrophy. Adapted with permission from the New England Journal of Medicine (31).

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

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