Study highlights need to include more African men in prostate cancer genetic testing
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Key takeaways:
- Researchers identified 39 deleterious variants in 113 Black South African men.
- Results show “the negative impact of continued exclusion of Africans and minorities groups in the genomics era.”
Guidelines are urgently needed to ensure inclusion of men of African ancestry in genetic testing for advanced, early-onset and familial prostate cancers, according to research in Journal of the National Comprehensive Cancer Network.
The findings of the study of southern African men “provide a rationale for considering lowering the pathologic diagnostic inclusion criteria and call for further genome-wide interrogation” to establish the most African-relevant prostate cancer gene panel possible, researchers concluded.
Rationale and methodology
“While running a genetic laboratory within the urology department in South Africa in the early 2000s, I noticed a disparity with regard to patients presenting with aggressive disease,” Vanessa M. Hayes, PhD, researcher at Ancestry & Health Genomics Laboratory of the Charles Perkins Centre at The University of Sydney, told Healio.
“There was a significant skewing toward men of African ancestry. That is when I first became interested in prostate cancer and discovered the research within the United States showing aggressive disease for African American men,” Hayes said.
A decade later, Hayes and colleagues established the Southern African Prostate Cancer Study (SAPCS).
“The goal of that study was to identify the genetic and nongenetic factors associated with this health disparity,” Hayes said. “It took another decade before we would attract international funding to perform the current research. Many pieces of the puzzle had to first be put in place. Africa and Africans were not yet included in the genomics era, with no ethical framework.”
The current first-of-its-kind study included 113 South African men with predominately advanced prostate cancer, for which researchers identified 21,899 single-nucleotide variants, 4,626 small insertions and deletions and 73 structural variants across 20 genes.
They used bioinformatic tools to identify the pathogenicity of the variants.
Findings
Researchers identified 39 deleterious variants. Further computational annotation classified 17 pathogenic and potentially oncogenic variants, including the rare CHEK2 Arg95Ter, BRCA2 Trp31Arg, ATM Arg3047Ter and TP53 Arg282Trp variants.
The cohort had a lower prevalence of rare pathogenic variants than the reported rate among non-African men with metastatic prostate cancer (5.8% vs. 11.8%).
Oncogenic variants of unknown pathogenicity included BRCA2 Leu3038Ile in a patient with early-onset disease. Conversely, those with FANCA Arg504Cys and RAD51C Arg260Gln reported a family history of prostate cancer.
Rare pathogenic and early-onset or familial-associated oncogenic variants occurred in 6.9% of patients presenting with a Gleason score of 8 or greater and 9.2% of patients presenting with a Gleason score 4 + 3.
“Currently, germline testing is proposed for men presenting with advanced prostate cancer, which is characterised as high-risk or very high-risk [pathological grade group 4] disease,” Hayes said. “Our study suggests the inclusion criteria for men of African ancestry be dropped from this pathological diagnostic grade group 4 to include intermediate-risk prostate cancer [pathological grade group 3]. Through the inclusion of intermediate-risk disease, we increased the number of identified pathogenic and early-onset or familial oncogenic variants by 1.3-fold.
“In addition, adopting these loosened criteria, we showed clinical value for only 30% of the gene panel, suggesting the potential of yet-unidentified genes of relevance in men of African ancestry,” Hayes said.
Implications
Although men of African ancestry have increased risk for prostate cancer and almost triple the risk for death, the benefits of germline testing to guide prognosis and treatment, and establish familial prevention strategies, are unavailable purely because of a man’s ethnicity, Hayes told Healio.
“No guidelines exist and germline testing panels have not been designed with the inclusion of men across the African diaspora,” she said. “The direct impact of our findings for African men with prostate cancer are therefore both scientific and moral. While we address the merit and importantly the limitations for African inclusion using current criteria, this study opens the doors to begin to establish new criteria, providing an entire ethnic group with hope that germline testing can change the current disparity in clinical outcomes. In turn, our study highlights the negative impact of continued exclusion of Africans and minorities groups in the genomics era.”
Hayes said oncologists and respective germline screening providers should work to establish a research and development arm tailored directly toward African inclusion.
“We need to move away from the one-size-fits-all model for prostate cancer care, and we need solutions to address African-relevant disparities in prostate cancer outcomes,” she said. “Additionally, there is an urgent need for further inclusion across the African diaspora to ensure a best possible African-relevant prostate cancer germline testing panel, which in turn will begin to address the significant disparity in prostate cancer outcomes for men of African ancestry. Historically, research has been conducted in non-African populations and translated to Africa. We argue for African tailored research to address a significant African-relevant problem.”
For more information:
Vanessa M. Hayes, PhD, can be reached at vanessa.hayes@sydney.edu.au.
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