Research has suggested that there may be a link between ancestral heritage and aggressive prostate cancer. Specifically, studies have found that men of African descent have a higher risk of developing and dying from aggressive prostate cancer compared to men of European or Asian descent.
Two groundbreaking studies published today in Nature and Genome Medicine found genetic signatures that explain ethnic differences in the severity of prostate cancer, particularly in Sub-Saharan Africa. The team discovered a new prostate cancer taxonomy (classification scheme) and cancer drivers by genetic sequencing of prostate cancer tumors from Australian, Brazilian, and South African donors, which not only distinguish patients by genetic ancestry, but also predict which cancers are likely to become life-threatening – a task that is currently difficult.
“A research focus on Western populations has severely limited our understanding of prostate cancer,” 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.
“Being of African descent or from Africa increases a man’s risk of developing lethal prostate cancer by more than doubling. While genomics holds the key to unraveling contributing genetic and non-genetic factors, data for Africa has been lacking until now.”
We revealed a novel prostate cancer taxonomy that we then linked to different disease outcomes using cutting-edge computational data science that allowed for pattern recognition that included all types of cancer variants.Dr. Weerachai Jaratlerdsiri
“Prostate cancer is the silent killer in our region,” said Professor Riana Bornman of the University of Pretoria, an international expert in men’s health and clinical lead for South Africa’s Southern African Prostate Cancer Study. “We had to start from the ground up, engaging communities in open discussion, laying the groundwork for African inclusion in the genomic revolution, and determining the true extent of prostate disease.”
Over two million cancer-specific genomic variants were identified in 183 untreated prostate tumors from men living across the three study regions using sophisticated whole genome sequencing (a method of mapping the entire genetic code of cancer cells).
“We discovered that Africans are affected by a greater number and spectrum of acquired (including cancer driver) genetic alterations, which has significant implications for ancestral consideration when managing and treating prostate cancer,” Professor Hayes said.
“We revealed a novel prostate cancer taxonomy that we then linked to different disease outcomes using cutting-edge computational data science that allowed for pattern recognition that included all types of cancer variants,” said Dr. Weerachai Jaratlerdsiri, a computational biologist from the University of Sydney and first author on the Nature paper.
“By combining our unique dataset with the largest public data source of European and Chinese cancer genomes, we were able to place the African prostate cancer genomic landscape into a global context for the first time.”
Dr. Tingting Gong, the paper’s first author, painstakingly sifted through genomic data for large changes in chromosome structure as part of her PhD at the University of Sydney (molecules that hold genetic information). Because of the complexity involved in computationally predicting their presence, these changes are frequently overlooked, despite their critical importance and contribution to prostate cancer.
“We showed significant differences in the acquisition of complex genomic variation in African and European derived tumours, with consequences for disease progression and new opportunities for treatment,” said Dr Gong.
This cancer genome resource is possibly the first and largest to include African data, in the world. “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.
“One of the study’s strengths was the ability to generate and process all data through a single technical and analytical pipeline,” Professor Hayes added. The study published in Nature and Genome Medicine is part of the late Archbishop Emeritus Desmond Tutu’s legacy. He was the first African to have his entire genome sequenced, providing data that would be used in genetic sequencing and prostate cancer research in southern Africa.
The results of the sequencing were published in Nature in 2010. “When the Archbishop was diagnosed with advanced prostate cancer at the age of 66 and died in late December 2021, he was an advocate not only for prostate cancer research in southern Africa, but also for the benefits that genomic medicine would offer all peoples,” Professor Hayes recalled.