Biological Differences in Prostate Cancers of African American and European American Men

An article published in Clinical Cancer Research found that the frequencies of genomic alterations in current therapeutic targets for prostate cancer were similar between African American and European American men, suggesting that existing precision medicine approaches could be equally beneficial if applied equitably.¹

However, the researchers did observe some novel differences between the 2 study populations, indicating that studies that profile large numbers of well-matched tumors from African American and non-African American men from the same clinical setting are necessary to confirm the novel associations reported in this study and to understand the clinical significance.

"These results reinforce the idea that there can be biological differences in prostate cancers between different ancestral groups and that samples from Black Americans need to be included in future molecular studies to fully understand these differences," co-corresponding author Joshua Campbell, PhD, assistant professor of medicine at Boston University School of Medicine, said in a press release.²

In order to identify genomic alterations associated with race, researchers compared the frequencies of somatic alterations in prostate cancer obtained from 4 publicly available datasets comprising 250 African American and 611 European American men, as well as a targeted sequencing dataset from a commercial platform of 436 African American and 3018 European American men.

In tumors from African American men, mutations in ZFHX3 along with focal deletions in ETV3 were more frequent. In addition, TP53 mutations were associated with an increasing Gleason score.

Further, MYC amplifications were more frequent in tumors from African American men with metastatic prostate cancer, whereas deletions in PTEN and rearrangements in TMPRSS2-ERG were less frequent in tumors from African American men. KMT2D truncations and CCND1 amplifications were more frequent in primary prostate cancer from African American men.

Overall, the researchers suggested that genomic features that could potentially impact clinical decision making were not significantly different between the 2 study populations including tumor mutation burden, microsatellite instability (MSI) status, and genomic alterations in select DNA repair genes, CDK12, and in AR.

“The poorer health outcomes we see in Black men with prostate cancer are not easily explained by any of the distinct gene mutations we identified in prostate tumors from men of African ancestry. This highlights the need to examine the environmental and social inequities that are well known to influence health outcomes across the board,” corresponding author Franklin Huang, MD, PhD, an assistant professor in University of California, San Francisco’s (UCSF’s) Division of Hematology/Oncology and member of the UCSF Helen Diller Family Comprehensive Cancer Center, UCSF Institute for Human Genetics, and UCSF Bakar Computational Health Sciences Institute, said in the release. “On the other hand, our tumor genomic analysis also showed that current precision medicine approaches ought to be as effective in Black Americans as they have been for other groups — if we can ensure that these drugs are applied equitably going forward."

Notably, the genomic differences observed in genes such as MYC, ZFHX3, PTEN, and TMPRSS2-ERG suggest that different pathways of carcinogenesis may be active in African American men, which could lead to further disparities if targeted therapies for some of these alterations become available. However, the researchers indicated that determining a comprehensive understanding of the genomic features of African American prostate cancers and how they relate to adverse features or contribute to poorer outcomes overall for African American men could inform future strategies to improve precision medicine for these patients.

“These types of studies will remain important to understand when certain therapies may preferentially benefit Black patients, who continue to remain underrepresented in clinical trials,” said Campbell.

References:

1. Yoga Y, Song H, Chalmers ZR, et al. Genomic Profiling of Prostate Cancers from Men with African and European Ancestry. Clinical Cancer Research. doi: 10.1158/1078-0432.CCR-19-4112.

2. Largest-Ever Study of Prostate Cancer Genomics in Black Men IDs Potential Targets for Precision Therapies [news release]. Published July 10, 2020. Accessed August 13, 2020. https://www.ucsf.edu/news/2020/07/418051/largest-ever-study-prostate-cancer-genomics-black-men-ids-potential-targets