Researching Answers in Africa

If your ancestors and relatives were dying from cancer at twice the rate of the rest of the population, wouldn’t you want someone to figure out why — and how to stop it?

This medical mystery makes cancer more deadly for a significant portion of Moffitt’s patients. To unravel the clues, Moffitt physician-scientists are reaching out to another continent: Africa. More than 5,500 miles from Tampa in Ghana, Moffitt is working on a collaboration that could help us understand why cancer is so much more prevalent — and deadly — among African American patients.

Consider: African American men are more than twice as likely as whites to die of prostate cancer. African American women are nearly twice as likely as whites to develop deadly triple-negative breast cancer. Both prostate and breast cancer are among the most common and aggressive forms of cancer in Ghana, where 98% of the population is Black. The same holds true for cancer in other parts of Africa.

What role might African heritage play in these cancers on separate continents? And how could understanding the biology of these cancers improve the odds for patients of African descent, here and worldwide?

“At Moffitt, our mission is to contribute to the prevention and cure of cancer. Understanding the disease and treating it better is in the wheelhouse of our mission. And quite often, we can learn a lot about cancer and its treatment by studying populations different than ours,” says Dr. Louis Harrison, chair of Moffitt’s Radiation Oncology Department. In addition to treating patients, Harrison is Moffitt’s chief partnership officer. “Nowhere in Moffitt’s mission statement does it limit our efforts to Tampa, Hillsborough County, Florida, or even the United States. We aspire to help everybody.”

Harrison and his fellow Moffitt radiation oncologist Dr. Kosj Yamoah, traveled to Ghana’s capitol city of Accra in November 2019 to further solidify this collaboration with several Ghanaian hospitals and universities. During a whirlwind week of seminars and meetings, they updated physician colleagues on the latest advances in radiation therapy. They formalized an agreement to allow select Ghanaian oncology residents to complete part of their studies at Moffitt. And they met with small groups of Ghanaian physician researchers to discuss next steps, publishing studies together and even someday conducting clinical trials collaboratively.

Why Ghana? It turns out that this Moffitt collaboration — as well as the complex tangle of African American genetic heritage — both trace origins back to this chunk of West Africa once known as the Gold Coast.

Moffitt Collaborator’s African Roots

At an age when most American kids are starting second grade, Kosj Yamoah was already the subject of news headlines in Ghana. The youngest of four, he taught himself to read by borrowing his siblings’ textbooks. He quickly surpassed his peers and made national news after acing Ghana’s high school entrance exam — at age 7. At boarding school with his siblings, Kosj became a de facto health officer by age 10. He routinely accompanied older students to the nearby hospital to act as a liaison with their physicians, fueling his interest in a medical career. “As much as I enjoyed studying and making my own discoveries,” he reflects, “I felt most alive when I was helping people recover.”

Yamoah was still completing his radiation oncology residency and fellowship in Philadelphia when he was awarded two highly competitive research grants. He’d already discovered the perfect intersection for his research and clinical interests: prostate cancer and its inordinate incidence and mortality among Black men, both in the U.S. and Africa.

“It made sense to focus my efforts on this disease,” says Yamoah. “I wanted to work with people globally to look at one common problem from both the advanced world and the developing world. So I started by looking at the landscape of prostate cancer in Ghana through the eyes of a tertiary institution, the Korle Bu Teaching Hospital in Accra. That’s really where the collaboration started.”

One of his first collaborators, fellow radiation oncologist Dr. Joel Yarney, now runs Ghana’s National Radiotherapy Oncology and Nuclear Medicine Centre at Korle Bu. He recalls Yamoah, then barely in his 30s, visiting the center to befriend him in research. “It didn’t require any formal ‘memorandum of understanding’ letters,” Yarney says with a laugh. “We became friends and started cooperating.”

Over the past nine years, Yamoah has made Yarney’s office his first stop on multiple trips to Ghana annually. The pair has even published studies together and share similar long-range visions of improving Black people’s odds against cancer no matter where they live. Getting there will take a series of steps. But Yamoah says it starts with simply showing up year after year.

“Having face-to-face interactions and the exposure to understand what you’re dealing with by being there, these are the things that build success,” notes Yamoah. “You also need time to build shared intellectual integrity and know that we’re here to help each other. It cannot be rushed.”

Despite spending half of his life in the U.S., Yamoah says he can still easily relate to his Ghanaian colleagues. “The lessons of childhood and understanding the culture don’t go away,” he says. Nor does his appreciation for what Ghanaians can do despite limits on resources and technology.

That, says Yarney, gives his Ghana-born colleague an edge in developing this collaboration. “When you’ve never been to a place like this, you can have the wrong perceptions about Africa and the underdeveloped world,” observes Yarney. “I think some of it stems from ignorance. All that the press would have us believe is the pictures they show in the media. But there is wide variation. Within a country, there may be resources, expertise that could be capitalized on for doing collaborative work.”

Once you’ve been to a place, you see many things you can no longer ignore — no matter how heart-wrenching they are.

Mapping the Source of African American Genes

They’re called castles; centuries-old fortified buildings with sweeping views of the Gulf of Guinea. The beauty of the setting belies their hideous history. They were built by Europeans as safe places to stash treasured African timber, ivory and gold before shipping it elsewhere for sale. But in the 1600s, as European colonization of the Americas grew, castle storerooms became dungeons to hold a newly valuable commodity: slaves — 17 million over four centuries, by some estimates — for shipment and sale in the New World.

The Cape Coast Castle 100 miles west of Accra is the second largest of 25 slave castles still standing along Ghana’s coast. Here, visitors descend 10 feet underground into a four-room dungeon lit only by small ventilation shafts high in one wall. The dungeon could hold hundreds of male prisoners, who sat and slept on bare rock with only a trench to carry away their wastes. Traces of their blood, urine, feces and even flesh are ground into the top layers of the dungeon floor. Conditions in the female slave dungeon are equally horrific, with the perverse addition of a hole in the wall for merchants and military to survey and select captives to rape.

Near the female dungeon, twin doors open to the sea and the last glimpse those captives who’d survived the castle would ever see of their native land. The “Door of No Return” led to ships that would carry them to lifelong servitude in the Americas.

“It’s a visit that leaves you speechless,” observed Harrison, who toured the castle along with Yamoah and more than 20 Korle Bu residents and students on their way to Harrison’s lecture at nearby University of Cape Coast. “This is a visit that makes you contemplate the generations that were lost to such depravity, captivity and unfairness. And it makes you want to redouble your efforts to try to give back what you can never give back, which is all that’s been taken away.”

Upstairs in the Cape Coast Castle, a museum recounts the pre-colonial cultures that populated this region. An auction block stands beside objects traded for slaves: glass beads, whisky bottles and the firearms to fight tribal wars that produced captives for sale.

But it’s a display map that drew Yamoah’s interest. The Triangular Slave Trade Route plots the path of European traders to various ports in Africa, where they’d trade weapons and baubles for enslaved people. Traders then sailed various transatlantic routes to ports in the Caribbean, and North and South America, where slaves were sold and ships were loaded with sugar, cotton, coffee and tobacco for the European market — and the triangular track started all over again.

“You’ll see versions of this same map in epidemiological studies,” says Yamoah. The routes illustrate how African genes were introduced to the Americas from colonial days through the Civil War.

Clearly, African Americans owe the bulk of their genetic makeup (82% by some estimates1) to ancestors who lived in Africa prior to the trans-Atlantic slave trade. There is European ancestry mixed in as well (16-17%1) — partly, it’s presumed, from the offspring of slaves and masters. But the native African genetic component is by no means uniform. It, too, is a stew of tribal lineage from across the world’s most genetically diverse continent2. The various paths laid out in Triangular Slave Trade Route maps provide clues as to where African captives might have been loaded onto ships for sale, but not where they originally came from.

In short, African Americans’ genetic makeup is a hodgepodge we don’t yet understand.

That’s critical to 21st century cancer care, with its focus on genetic mutations that drive cancer and genetic biomarkers that give clues to its treatment. Most of what we know and have harnessed to fight cancers in specific populations (like BRCA mutations and breast cancer) has been based on work with patients of European ancestry.

What might researchers uncover if they could understand African Americans’ complicated genetic heritage? For Yamoah, a key step is being able to draw comparisons to the source, in Africa. That means comparing not only their genetic makeup but also the epigenetic changes in similar tumors from both continents. The comparisons might lead to subtle changes in diagnosis and treatment that could reduce cancer disparities for all patients of African descent.

“We are moving very rapidly to an era where medicine will be practiced at an individual level,” says Yamoah. “I believe that, if the African continent is not at the forefront of these discoveries, we will only stand to worsen the disparities gap, where we will not know how to treat people of African origin because we haven’t done the work when it was time to.”

Thanks to the progress being made by this collaborative effort, that time is near.

Medical students, professors and physicians at the University of Cape Coast attend a special lecture, one of several presented by Drs. Louis Harrison and Kosj Yamoah at universities and hospitals during their November 2019 visit.

The Foundation Laid Thus Far

It may be years before physician scientists in Ghana have the tools to preserve tissue samples and data in a biorepository that could foster international collaborative research into all types of cancers in patients of African descent. But thanks to Yamoah and Moffitt’s collaborative efforts with Yarney and the National Radiotherapy Oncology and Nuclear Medicine Centre at Korle Bu, a solid foundation has been laid.

During last November’s visit, Yamoah and Harrison witnessed some major milestones.

• A retrospective clinical database with diagnosis and treatment details of all Korle Bu prostate and breast cancer patients from 2003 to 2019 has been culled from thousands of paper medical charts. The Korle Bu staff and trainees who assembled the database under Yamoah’s and Yarney’s guidance now know much more about how data needs to be tracked for future research and clinical trials.
• Ghana now boasts 15 radiation oncologists whose skills can be deployed to fight all types of cancers, unlike surgical or chemotherapy approaches. To put it in perspective, Ghana’s 15 radiation oncologists must serve a nation of 30 million, while Moffitt alone has 15 radiation oncologists on its staff.
• Six more radiation oncology residents are in the education pipeline, and the Ghana College of Physicians and Surgeons formalized an agreement to allow select residents to earn credit for studying at Moffitt for six months to a year.
• The first two Ghanaian physicians who traveled to Moffitt for study, Drs. Francis Asamoah and Hannah Ayettey-Anie, have now returned to Korle Bu with deepened skills on newer technologies and exciting ideas for the future.
• After years of lobbying Ghana’s Ministry of Health for funding, the National Radiotherapy Oncology and Nuclear Medicine Centre at Korle Bu has a new building and new equipment to provide radiation therapy to more than 1,600 patients per year. This includes five new planning systems, an on-site CT scanner and the center’s new linear accelerator. It’s capable of delivering radiation more precisely to tumors deeper in the human anatomy than the workhorse cobalt-60 machine that has served patients for more than 20 years. The new technology means Korle Bu will be able to deliver treatments comparable to many of those provided at Moffitt, opening the way to greater comparative research within the Moffitt/Korle Bu collaboration.
• Some of the trainees that Yamoah and Yarney have worked with through the years are now faculty at institutions throughout Ghana, and they maintain a willingness to be part of research efforts going forward. In fact, some have even helped to gather data and biopsy samples from Ghanaian prostate cancer patients for comparative analysis with those of African American patients treated at Moffitt.

As the collaboration deepens and progresses, Yamoah can see a future that will benefit patients at Moffitt and in Ghana and well beyond.

“Ten years down the line, I want to see that we understand the biology now and we can actually offer the personalized care to every human being on the planet as needed. I think that’s the responsibility whether you are Black or white: to make sure that whatever scientific exploration you’re doing is helping humanity in an equitable way. That’s what I want to see.”

Citations:

1. Baharian S, Barakatt M, Gignoux CR, Shringarpure S, Errington J, Blot WJ, et al. (2016) The Great Migration and African-American Genomic Diversity. PLoS Genet 12(5): e1006059. doi:10.1371/ journal.pgen.1006059
2. Stefflova K, Dulik MC, Barnholtz-Sloan JS, Pai AA, Walker AH, et al. (2011) Dissecting the Within-Africa Ancestry of Populations of African Descent in the Americas. PLoS ONE 6(1): e14495. doi:10.1371/journal.pone.0014495