Researchers have revealed how the lack of genomic research for individuals with African ancestry—particularly those from the Sub-Saharan region—may be hampering efforts to reduce disparities for patients with prostate cancer, according to a new study published by Gheybi et al in JNCCN–Journal of the National Comprehensive Cancer Network.
Background
In 2020, the GLOBOCON studies identified the regions of the world most impacted by prostate cancer mortality, which include populations with significant African ancestry such as the Caribbean and the regions of Sub-Saharan Africa—with mortality rates 3.4- and 2.5-fold greater, respectively, than the overall U.S. population. Within the United States, Black individuals have a 2.3 to 5 times increased risk of prostate cancer–associated mortality compared with non-Black individuals.
“Although [male patients with] African ancestry have the highest incidence rates for aggressive prostate cancer and associated death globally, [because of a] lack of available data, no tailored testing criteria have been established for such populations at increased risk” stressed lead study author Kazzem Gheybi, MD, PhD, a postdoctoral research fellow at the University of Sydney.
“The African diaspora is highly diverse, so I caution against regarding the most genetically diverse population in ‘singular’ terms,” emphasized senior study author Vanessa M. Hayes, PhD, the Petre Chair of Prostate Cancer Research at the University of Sydney School of Medical Sciences, Extraordinary Professor at the University of Pretoria School of Health Systems & Public Health, and Honorary Professor of Health Sciences at the University of Limpopo. “What is required is [a] concerted effort for inclusion that takes a grassroots approach.”
She added: “We need to build criteria based on population-specific knowledge. We encourage cancer care and germline screening providers to establish a research and development arm tailored specifically for African inclusion. We need to move away from the one-size-fits-all model for prostate cancer care; African solutions should address African-relevant disparities in prostate cancer outcomes.”
Study Methods and Results
In the new study, the researchers evaluated molecular genetic results for 113 Black South African patients diagnosed with advanced prostate cancer to find evidence for increased and potentially unique genetic testing recommendations.
The study involved a close examination of 21,899 single-nucleotide variants, 4,626 small insertions and deletions, and 73 structural variants across 20 genes from the 113 patients. After initially excluding variants that were known not to be cancer-causing, the researchers found 38 mutations across 52 patients and identified a total of 17 variants—4 pathogenic and 13 potentially oncogenic.
The researchers noted that the patients involved in the study had a 5.6% rate of rare cancer-causing variants—which was significantly lower than the established rate of 11.8% for non-African patients with confirmed metastatic prostate cancer. The researchers suggested that a decreased sensitivity of current gene panels for risk assessment in this patient population explained the lower rate of variants.
Conclusions
“This study opens the door to begin to establish new criteria, providing [male patients who have] African ancestry with hope that germline testing can change current disparities in clinical outcomes,” commented Dr. Gheybi.
“This study highlights the poor clinical utility (30%) of the currently most-utilized germline testing panels in [male patients with] African ancestry, largely [because of] minimal inclusion of these groups in the development of the panels,” said Samuel L. Washington III, MD, MAS, the Goldberg-Benioff Endowed Professor of Cancer Biology and Assistant Professor of Urology at the University of California, San Francisco Helen Diller Family Comprehensive Cancer Center as well as a member of the NCCN Clinical Practice Guidelines in Oncology Panel for Prostate Cancer Early Detection.
He concluded: “This study emphasizes two crucial domains: it provides further evidence of the need for greater inclusivity in genetic panel development and it recognizes that disparities in outcomes for [male patients with] African ancestry can’t be explained solely by the findings in 113 Black South African [patients]. Although the NCCN Guidelines for Prostate Cancer Early Detection identify Black identity as a risk factor, the panel notes the contributions of poor access to care, social determinants of health/social risk, and heritable genes to these observations. I look forward to further research in this area that examines how the limitations of our current tools can be improved to better reflect the populations we serve.”
Disclosure: For full disclosures of the study authors, visit jnccn.org.
