Genetic signatures identified in prostate cancer patients explain ethnic differences in the severity of the disease, particularly in Sub-Saharan Africa, according to two pioneer studies published simultaneously in Nature and Genome Medicine.
According to one of the authors, being of African descent more than doubles the risk of lethal prostate cancer. However, the researchers believe that “genomics holds a critical key to unraveling contributing genetic and non-genetic factors, data for Africa has till now, been lacking.”
“Our understanding of prostate cancer has been severely limited by a research focus on Western populations,” said senior author Professor Vanessa Hayes, genomicist and Petre Chair of Prostate Cancer Research at the University of Sydney’s Charles Perkins Centre and Faculty of Medicine and Health in Australia.
According to Riana Bornman, clinical lead for the Southern African Prostate Cancer Study in South Africa, prostate cancer is a silent killer in South Africa, and a system is needed to include Africans in the genomic revolution.
“We had to start with a grassroots approach, engaging communities with open discussion, establishing the infrastructure for African inclusion in the genomic revolution, while determining the true extent of prostate disease,” Bornman said.
The researchers from the nature study used sophisticated whole genome sequencing to identify over two million cancer-specific genomic variants in 183 untreated prostate tumors from men across the study’s three regions (African, European, African-European admixed). The researchers identified some findings peculiar to African ancestry, including a high tumor mutational burden, increased percentage of genome alteration, a greater number of predicted damaging mutations, and a higher total of mutational signatures.
“We found Africans to be impacted by a greater number and spectrum of acquired (including cancer driver) genetic alterations, with significant implications for ancestral consideration when managing and treating prostate cancer,” said Professor Hayes.
“Using cutting-edge computational data science which allowed for pattern recognition that included all types of cancer variants, we revealed a novel prostate cancer taxonomy which we then linked to different disease outcomes,” said Dr. Weerachai Jaratlerdsiri, a computational biologist from the University of Sydney and first author on the Nature paper. He added that combining their unique dataset with the largest public data source of European and Chinese cancer genomes allowed them to “place the African prostate cancer genomic landscape into a global context for the first time.”
Dr. Tingting Gong, first author of the Genome Medicine paper, as part of how Ph.D. looked through genomic data for major alterations in chromosome structure. Her research found significant disparities in the accumulation of complex genomic variation between African and European tumors. This discovery has “consequences for disease progression and new opportunities for treatment,” according to Dr. Gong.
“Through African inclusion, we have made the first steps not only towards globalizing precision medicine but ultimately to reducing the impact of prostate cancer mortality across rural Africa,” explains Professor Bornman.
Source: Science Daily
Journal source: Nature and Genomedicine