Genetic signature that explains racial differences in prostate cancer severity

Senior author Professor Vanessa Hayes, a genomicist and Patras Prostate Cancer Research Chair at the University of Sydney’s Charles Perkins Centre and School of Medicine and Health, said: “Our understanding of prostate cancer has been underpinned by research focused on Western populations. Serious limitation.

Being of African descent or from Africa, men more than double their risk of fatal prostate cancer. While genomics holds the key to unraveling genetic and non-genetic factors, data from Africa have so far been lacking. “

Professor Riana Bornman from the University of Pretoria said: “Prostate cancer is the silent ‘killer’ in our region. We must start at the grassroots level, engaging the community in open discussions and building the infrastructure for Africans to integrate into the genomic revolution, while identifying prostate The true extent of the disease.”

She is an international expert in men’s health and clinical lead for the Southern Africa Prostate Cancer Study in South Africa.

Using advanced whole-genome sequencing (a method of mapping the entire genetic code of cancer cells), researchers identified more than 2 million cancer-specific genomic variants in 183 untreated prostate tumors residing in three study areas .

“Our findings that Africans are affected by a greater number and range of acquired genetic alterations, including cancer drivers, have important implications for ancestry considerations in the management and treatment of prostate cancer,” Professor Hayes said.

Dr Weerachai Jaratlerdsiri, a computational biologist at the University of Sydney and first author of Nature, said: “Using advanced computational data science that allows pattern recognition to include all types of cancer variants, we have revealed a new classification of prostate cancer. method, which we then correlate with different disease outcomes.”

“Combining our unique dataset with the largest public data sources on cancer genomes in Europe and China allows us to place the genomic map of prostate cancer in Africa in a global context for the first time.”

As part of her PhD at the University of Sydney, Dr Tingting Gong, lead author of the Genomic Medicine paper, painstakingly sifted through genomic data looking for dramatic changes in the structure of chromosomes, the molecules that hold genetic information. 

These changes are often overlooked because of the complexity involved in computationally predicting their presence, but this is an area of ​​critical importance and contribution to prostate cancer.

“We show that African- and European-derived tumors differ significantly in their acquisition of complex genomic variations, with implications for disease development and new opportunities for treatment,” said Dr. Gong.

This cancer genome resource is probably the first and largest resource in the world to include African data.

Professor Bornman explained: “By including data from Africa, we are not only taking the first steps towards the globalisation of precision medicine, but ultimately reducing the impact of prostate cancer on rural areas across Africa.”

Prof Hayes added: “One strength of this research is the ability to generate and process all the data through a single technical and analytical pipeline.”

The research in the Nature and Genomic Medicine papers is part of the legacy of the late Archbishop Emeritus Desmond Tutu. 

He was the first African to have his entire genome sequenced, data that will become an integral part of genetic sequencing and prostate cancer research in southern Africa.

 The results of the sequencing were published in the journal Nature in 2010.

Professor Hayes recalled: “The Archbishop, who was diagnosed with advanced prostate cancer at the age of 66 and died at the end of December 2021, was an advocate not only for prostate cancer research in southern Africa, but also for the benefits that genomic medicine will bring to all people. “

“We hope this study is the first step toward that goal.”