Prostate cancer appears to run in some families, implying that there may be an inherited or genetic factor in some cases. Nonetheless, the majority of prostate cancers occur in men who have no family history of the disease. A man’s risk of developing prostate cancer is more than doubled if his father or brother has the disease.
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.
“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.
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. Our understanding of prostate cancer has been severely limited by a research focus on Western populations.
Professor Hayes
“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.”
“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.”
Through sophisticated whole genome sequencing (a way of mapping the entire genetic code of cancer cells), over two million cancer-specific genomic variants were identified in 183 untreated prostate tumours from men living across the three study regions.
“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.
“Combining our unique dataset with the largest public data source of European and Chinese cancer genomes allowed us to, for the first time, place the African prostate cancer genomic landscape into a global context.”
Dr. Tingting Gong, the paper’s first author, painstakingly sifted through genomic data for large changes in the structure of chromosomes as part of her Ph.D. at the University of Sydney (molecules that hold genetic information). Because of the difficulty in computationally predicting their presence, these changes are frequently overlooked, despite their critical importance and contribution to prostate cancer.
“We found significant differences in the acquisition of complex genomic variation in African and European derived tumors, with implications for disease progression and new treatment options,” Dr. Gong said.
This cancer genome resource is possibly the world’s first and largest to include African data. “Through African inclusion, we have made the first steps not only towards globalising precision medicine but ultimately to reducing the impact of prostate cancer mortality across rural Africa,” explains Professor Bornman.
“A strength of this study was the ability to generate and process all data through a single technical and analytical pipeline,” added Professor Hayes.
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 sequencing results 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.
