Racial Differences in Genomic Profiles of Primary and Metastatic Prostate Cancer
In a letter to the editor published in The New England Journal of Medicine, Brandon A. Mahal, MD, and colleagues described genomic differences in prostate cancer in Black, White, and Asian men.
Brandon A. Mahal, MD
Study Details
The study involved next-generation sequencing data from patients who had been treated for prostate cancer at Memorial Sloan Kettering Cancer Center or Dana-Farber Cancer Institute. Among the total of 2,393 patients, 2,109 were White; 204, Black; and 80, Asian. A total of 1,484 patients had primary disease (1,308 White, 133 Black, and 43 Asian) and 909 had metastatic disease (801 White, 71 Black, and 37 Asian).
Key Findings in Primary Disease
- Among patients with primary disease, a higher proportion of Asian patients had more than 20 mutations (11.5%) compared with Black or White men (< 5% each).
- FOXA1 mutations were found more frequently in Black (18.6%, P = .003) and Asian men (37.8%, P < .001) vs White men (11.9%). TP53 mutations were more common in White men vs Black men (20.6% vs 14.2%, P = 0.045). Mutations in the androgen receptor (AR) gene were uncommon, irrespective of race (< 3%).
- The frequency of genes with actionable mutations (approximately 17%–22%) and the frequency of mutations in DNA-repair genes (approximately 10%–14%) did not markedly differ among groups.
Key Findings in Metastatic Disease
- Among men with metastatic disease, a higher proportion of Black men had more than 20 mutations (6.8%) compared with White or Asian men (< 3%).
- AR mutations were more frequent in Black vs White men (18.3% vs 8.1%, P = .004; approximately 5% in Asian men). TP53 mutations were more common in Asian men (62.0%) vs Black men (22.5%, P = .008) or White men (36.4%, P = .004).
- Genes with actionable mutations (26.7% vs 18.0%, P = .05) and mutations in DNA repair genes (22.5% vs 15.6%, P = .05) were more common in Black men vs White men. Frequencies in Asian men were approximately 18% and 8%, respectively.
- BRAF mutations were more common in Black men vs White men (7.0% vs 1.5%, P = .002). As noted by the investigators, such mutations are rare in prostate cancer and are considered to be actionable for many tumor sites.
The investigators concluded, “Clinically significant alterations may occur at different frequencies across races. Notably, Black men with metastatic prostate cancer were more likely than either White or Asian men to have tumor mutations in AR, along with mutations in DNA-repair genes and actionable genetic mutations. This finding could have implications for prognosis, response to therapy, and enrollment of minority populations in clinical trials and precision oncology studies…To support and further explore the implications of these findings, we will need studies involving a larger number of non-White men for whom data are available regarding the effects of treatment and results from histopathological analysis on outcomes. The evaluation of such data could help to prevent a worsening of racial disparities in the diagnosis and treatment of prostate cancer.”
Disclosure: The study was supported by the American Society for Radiation Oncology, Prostate Cancer Foundation, U.S. Department of Defense, and National Institutes of Health. For full disclosures of the study authors, visit nejm.org.
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