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

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 3

Movement toward a proactive prostate cancer risk stratification approach to disease control for improvement of prostate cancer mortality and elimination of disparities.

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Movement toward a proactive prostate cancer risk stratification approach...
(A) Guidelines differ as to when men in the general US population should undergo prostate cancer screening via PSA test and digital rectal examination; and how Black men should best be screened has also been debated (165–167). Screening detects prostate cancer at an early stage, at a cost of significant overdiagnosis and overtreatment. The use of active surveillance approaches for low-risk prostate cancer to mitigate this problem is not evenly distributed between White and Black men or among men of higher versus lower socioeconomic status (167). (B) A future paradigm might feature risk stratification, using germline genetic testing (for risk alleles associated with European or African ancestry), midlife PSA testing, and an inventory of diet, lifestyle, and family history. Men at high risk could be steered toward more vigilant prostate cancer screening regimens and coached to pursue substantive dietary modification, weight loss, and exercise, while men at low risk might not need such aggressive intervention. Prostate cancer screening itself is somewhat limited by health care access, and this new precision paradigm of risk ascertainment and intervention could be even more sensitive to social determinants of health and health care inequities.