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The complex interplay of modifiable risk factors affecting prostate cancer disparities in African American men

Nature Reviews Urology (2024)Cite this article

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Abstract

Prostate cancer is the second most commonly diagnosed non-skin malignancy and the second leading cause of cancer death among men in the USA. However, the mortality rate of African American men aged 40–60 years is almost 2.5-fold greater than that of European American men. Despite screening and diagnostic and therapeutic advances, disparities in prostate cancer incidence and outcomes remain prevalent. The reasons that lead to this disparity in outcomes are complex and multifactorial. Established non-modifiable risk factors such as age and genetic predisposition contribute to this disparity; however, evidence suggests that modifiable risk factors (including social determinants of health, diet, steroid hormones, environment and lack of diversity in enrolment in clinical trials) are prominent contributing factors to the racial disparities observed. Disparities involved in the diagnosis, treatment and survival of African American men with prostate cancer have also been correlated with low socioeconomic status, education and lack of access to health care. The effects and complex interactions of prostate cancer modifiable risk factors are important considerations for mitigating the incidence and outcomes of this disease in African American men.

Key points

  • Current data emphasize the need for the United States Preventive Services Task Force (USPSTF) to re-evaluate their guidelines by recommending prostate cancer screening in high-risk populations to attenuate the upward trends of prostate cancer fatalities and reduce disparities.

  • 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhiP)–DNA adducts can facilitate mutagenesis that may result in tumorigenesis. Data suggest that African American men might have diets that include higher amounts of red meat and sources of PhiP than European American men, contributing to the prostate cancer disparities observed.

  • Vitamin D deficiency has been shown to be associated with aggressive prostate cancer and mortality, especially in African American men. Elucidating vitamin D signalling pathways that underlie prostate carcinogenesis might aid mitigation of prostate cancer disparities between African American and European American men.

  • Glucocorticoid receptors have emerged as a major driver of prostate cancer progression and resistance to treatments. Clinicians must consider the possibility of differential responses to prostate cancer treatments, including glucocorticoid treatments in African American men.

  • Increasing the number of studies investigating immunity and inflammatory regulation in prostate tumours and adjacent tumour microenvironment is imperative for high-risk under-represented populations.

  • Sensitive and strategic initiatives to advance inclusive research are needed to increase clinical trial participation by minority individuals.

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Fig. 1: Global prostate cancer incidence and mortality by world areas.
Fig. 2: US prostate cancer incidence and mortality rates by race.

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Acknowledgements

The authors thank Morehouse School of Medicine and the Division of Health Equities at City Hope for support. J.R.J. acknowledges the support received from NIH/NCI: U54CA118638 and NIH/NIMHD 2U54MD007602-36. L.W.-B. is grateful for the support received from 1T32CA186895, the Prostate Cancer Foundation Young Investigator award (20YOUN04), the Department of Defense Prostate Cancer Research Program Early Investigator award (W81XWH2110038), and the NIH KL2TR002381.

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Authors and Affiliations

  1. Department of Microbiology, Biochemistry & Immunology, Morehouse School of Medicine, Atlanta, GA, USA

    Jabril R. Johnson

  2. Department of Physiology, Morehouse School of Medicine, Atlanta, GA, USA

    Nicole Mavingire & Leanne Woods-Burnham

  3. Department of Diabetes and Cancer Metabolism, Beckman Research Institute, City of Hope Comprehensive Cancer Center, Duarte, CA, USA

    Mya Walker

  4. Department of Community Health and Preventive Medicine, Morehouse School of Medicine, Atlanta, GA, USA

    Deyana Lewis, Brian Rivers & Rick A. Kittles

  5. Department of Population Sciences, Division of Health Equities, City of Hope Comprehensive Cancer Center, Duarte, CA, USA

    Stanley E. Hooker & Dorothy Galloway

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Contributions

J.R.J., N.M., L.W.-B., M.W., D.L. and B.R. researched data for the article. J.R.J., N.M., L.W.-B., M.W., D.L. and B.R. wrote the article. J.R.J., N.M., L.W.-B., M.W., D.L. and B.R. substantially contributed to the discussion of content. J.R.J., N.M., L.W.-B., D.L., S.E.H., D.G., B.R. and R.A.K. reviewed and edited the manuscript before submission.

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Johnson, J.R., Mavingire, N., Woods-Burnham, L. et al. The complex interplay of modifiable risk factors affecting prostate cancer disparities in African American men. Nat Rev Urol (2024). https://doi.org/10.1038/s41585-023-00849-5

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