Studies Reveal Aggressive Prostate Cancer Linked to Ancestral Heritage

By Leah Lawrence - Last Updated: September 7, 2022

Researchers have identified genetic signatures that may explain the ethnic differences in the severity of prostate cancer, particularly in sub-Saharan Africa.

In two studies published in Nature and Genome Medicine, researchers detailed how they used genetic sequencing of prostate cancer tumors from Australian, Brazilian, and South African donors to identify a new prostate cancer taxonomy and cancer drivers that not only distinguish patients by genetic ancestry, but also predict which cancers are likely to become life-threatening.

“Our understanding of prostate cancer has been severely limited by a research focus on Western populations,” said senior author 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, more than doubles a man’s risk for lethal prostate cancer. While genomics holds a critical key to unravelling contributing genetic and non-genetic factors, data for Africa has till now, been lacking.”

In the Nature study, the researchers used whole-genome sequencing of treatment-naïve prostate cancer samples from 183 ancestrally and globally distinct patients. They generated a large cancer genomics resource for sub-Saharan Africa, identifying around 2 million somatic variants.

“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 Hayes.

Among the significant findings were elevated tumor mutational burden, increased percentage of genome alteration, a greater number of predicted damaging mutations, and a higher total of mutational signatures. Additionally, they identified driver genes NCOA2, STK19, DDX11L1, PCAT1 and SETBP1.

In the Genome Medicine study, the researchers used whole genome sequencing and best practice workflows to analyze structural variations for 180 prostate tumors derived from 115 African, 61 European, and four ancestrally admixed patients.

In African-derived tumors there was a 1.6- to 2.5-fold increase in duplication events. African-derived tumors were also twofold more likely to present with a hyper-SV subtype.

“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 University of Pretoria’s Professor Riana Bornman, an international expert in men’s health and clinical lead for the Southern African Prostate Cancer Study in South Africa.

References

Study reveals aggressive prostate cancer linked to ancestral heritage

African-specific molecular taxonomy of prostate cancer

Genome-wide interrogation of structural variation reveals novel African-specific prostate cancer oncogenic drivers

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