The First African Genome and the Search for Answers on Prostate Cancer Disparities

Vanessa M. Hayes, PhD, grew up in South Africa during apartheid, when every citizen was assigned numbers that dictated where they could live, what school they could attend, who they could marry, and more. As a white South African, her number was on the privileged side of things, but she witnessed the violence and turmoil this system created. The experience left her deeply opposed to exclusion in any form, including in science.

While studying genetic susceptibility to HIV in South Africa in the early 2000s, Hayes noticed a troubling pattern: Drugs developed and tested in the United States were often less effective in African patients. Soon after, the Human Genome Project released its first draft of the human genome, yet this map of DNA included genetic data from just one African individual. For Hayes, these examples underscored a deeper problem: Science was being done “back to front.”

“So many studies are done on white people and then the results are interpreted onto African people, which was never going to work because it is doing research backwards,” Hayes, who is now head of the Ancestry and Health Genomics Laboratory at the Charles Perkins Centre at the University of Sydney in Australia, explained to Cancer Research Catalyst. “Instead, I knew if we worked on African people and translated findings the other way around, it would work better because Africans have more diversity. But Africans were just purely excluded from genomics and precision medicine.”

Hayes wanted to change that.

Following the widely condemned remarks about Africans’ genetics and intelligence by James D. Watson, PhD, FAACR, the first person to sequence the human genome using the then brand-new technology called next-generation sequencing (NGS), Hayes told a colleague, “We’re going to sequence Nelson Mandela.” That colleague’s institution had just acquired NGS technology.

A few years later, Hayes and her colleagues published the first complete African human genome. And while they didn’t sequence Nelson Mandela’s genome, the study did include another well-known South African: Nobel Peace Prize winner Archbishop Desmond Tutu.

For Hayes, sequencing the first African genome was never the end goal, it was a starting point. Her passion is in understanding why men of African ancestry face disproportionate burdens from prostate cancer. Today, mortality rates for Black men with prostate cancer are two times higher compared with white men in the United States and three times higher in sub-Saharan Africa compared with global estimates. But long before any statistics like that were known, Hayes witnessed this disparity firsthand while working in the genetics lab of a Cape Town hospital’s urology department.

“Even though this hospital served a predominantly mixed-race population, what we call Cape Coloured, almost all of the patients I would see walking past my lab with prostate cancer were Black,” Hayes told Cancer Research Catalyst.

Her desire to understand why—and shed light on a disparity few people were talking about back then—has led to several groundbreaking discoveries that have fundamentally changed how scientists understand the relationship between ancestry, genetics, and disease. For her contributions to this field, Hayes was awarded the 2026 AACR Distinguished Lectureship during the 19th AACR Conference on The Science of Cancer Health Disparities where she shared updates about her research and efforts to close the gap in prostate cancer outcomes.

Assembling the First African Genome

Hayes started her lecture with a look back at her past research, including the launch of the Southern African Prostate Cancer Study (SAPCS) in 2008 to examine potential genetic and environmental factors driving the aggressive form of this disease in African men. The program began in the rural South African province of Limpopo, which Hayes explained is about the same size as Mississippi but with double the population. While Mississippi has about 100 urologists today, Limpopo only had one at that time for its 6 million people.

So, Hayes and her team started from scratch by training community health care members and engaging with tribal elders, healers, and herbalists to get the various tribes on board. As a child, her parents would take her on trips through remotes part of Africa, during which she learned how to respect different cultures. Those experiences came in handy as Hayes worked to build trust with the indigenous communities.

“I think the biggest mistake people make is they think that because someone can’t read or write, they’re not intelligent,” Hayes told Cancer Research Catalyst. “In fact, these are highly, highly intelligent people.”

By treating the people in these communities with respect, she found they were eager to participate in the study. When Hayes was looking for participants willing to sequence their genome for her landmark African genome study, she recruited four indigenous hunter-gatherers—!Gubi, G/aq’o, D#kgao, and !Aî. But getting Archbishop Tutu to participate was a little more challenging.

As a prominent religious figure—which was very important in Africa—Tutu checked a lot of the boxes to be the first African to have their genome sequenced. He understood what Hayes was trying to accomplish. He knew about the Human Genome Project. He knew what the significance of this would be for Africa. And, he had prostate cancer. But his advisors didn’t want him to do it.

During an hour-long meeting filled with many arguments, Tutu spoke to end a particularly heated exchange. “Gentlemen,” Hayes recalled him saying, “no fighting in my office. I won the Peace Prize!” Then, once the hour came to an end, he got up, pointed to each member of his council, and said, “You, you, and you say no. But I say yes.”

Thanks to this study, and Tutu’s participation, Hayes and her team identified 1.3 million genetic variants that were new to the Single Nucleotide Polymorphism Database (dbSNP). But Hayes said so much more work is needed to fully understand the African genome.

“What is shocking is still today, only roughly 2% of all whole genomes actually represent the African continent,” she said. “We can’t just restrict our analysis to African Americans because that means we are not capturing the African continent.”

What is shocking is still today, only roughly 2% of all whole genomes actually represent the African continent.

What Genomics Revealed About Prostate Cancer Disparities

One of the messages that Hayes wanted to get across during her lecture is the need to demystify the term “African.”

“This is a continent of 2,000 languages. This is the continent where we all come from,” she said to help illustrate both the diversity and prevalence of the African genome.

Hayes likened the genetic diversity of the world to a family tree with Africa at the roots because it is the origin of the human species. Hayes then explained how the earliest known indigenous people of Southern Africa (the Khoe-San)—who would be closer to the base of the tree—have the greatest amount of genome variation. But as smaller groups left Africa for other continents, like Europe or Asia, those branches had less genetic diversity.

So, why does this matter when it comes to prostate cancer? Hayes’ work examining the African genome is providing a more comprehensive understanding of prostate cancer biology across a diverse patient population.

For example, in one study, her team found that compared with white and Black Americans, South-East African patients with prostate cancer are threefold more likely to be diagnosed with advanced disease. But within Africa, men from the east are 1.5 times more likely to present with advanced disease than those from the south.

They also found that current germline testing panels used to identify risk and potential treatment options for prostate cancer are less effective for Southern African men compared with European men. However, her team was able to identify potential gene variants that may improve these germline testing panels for African men. Other current tests that they found less suitable for African men include the commonly used prostate-specific antigen (PSA) for screening as well as prediction tools for polygenic risk and to determine if a variant is pathogenic or not.

“We have to go back to the drawing board and design our tools and our workflows to be appropriate for African populations,” Hayes said.

While prostate cancer typically has a low tumor mutational burden, her team discovered that men of African ancestry are prone to tumors with high mutational burden. This can be an indicator of environmental factors playing a role in cancer’s development, Hayes said.

“A tumor genome carries a scar of your past, so everything you are exposed to in utero all the way to the time your tissue is taken is evidence of what has happened,” she explained. “We call these tumor mutational signatures.”

This brings Hayes back to the overarching goal of SAPCS: to discover all the potential drivers of prostate cancer in African men. She is now continuing that work thanks to a Health Equity Research Outcomes and Improvement Consortium (HEROIC) Award funded by the U.S. Department of Defense. Through the HEROIC Prostate Cancer Precision Health Africa1K study, her team is merging genomics data with clinical, lifestyle, and biochemical/environmental data to generate the largest prostate cancer resource of its kind in Africa to ultimately help deliver advances that could make an impact for patients everywhere.

Archbishop Tutu passed away from cancer in 2021, before he could see how his contributions to science help benefit patients like him. But his words, nevertheless, have become a motto for Hayes’ research: “There comes a point where we need to just stop pulling people out of the river. We need to go upstream and find out why they are falling in.”