Colorectal cancer is common — and deadly — around the world.
But too often, major population groups are not represented in colorectal cancer research, which focuses mainly on patients in America and Western Europe.
A team of researchers from Memorial Sloan Kettering Cancer Center, joined by colleagues in Nigeria, recently published important research in Nature Communications that provides surprising insights into colorectal cancer in Nigeria and West Africa.
This research compared the tumor genomics and other differentiating factors of colorectal cancer patients in Nigeria with patients at MSK, who closely mirror patients across the United States.
What the team found has implications for treating patients in West Africa and provides a roadmap for understanding how different population groups may require very different approaches to save lives.
Peter Kingham is an MSK surgeon who cares for people with colorectal and other gastrointestinal cancers. He has spent decades visiting sub-Saharan Africa as a surgeon and medical educator. As the Director of MSK’s Global Cancer Disparities Initiatives, he led the teams that conducted this new research.
What stood out in your comparison of Nigerian colorectal cancer patients with those in America?
There were significant differences. In Nigeria, the average age of colorectal patients is younger: early 50s versus mid-60s in America.
Patients in Nigeria are also usually diagnosed at a more advanced stage of the disease. Most have stage 3 and 4 cancer when diagnosed. In America, only about 1 in 5 patients have advanced colorectal when first diagnosed.
Patients in Nigeria also are more likely to have rectal cancer than patients in America, who are more likely to have colon cancer. Rectal cancers sometimes can’t be operated on because the tumor sits inside the narrow part of the pelvis and is very close to organs like the bladder or vagina or the spine.
In comparison, a colon tumor in the middle of the abdomen can grow to the size of a bowling ball and still be operated on.
What do these differences mean for patient outcomes?
These differences mean outcomes are much poorer for patients in Nigeria compared with the US.
In Nigeria, the survival rate for colorectal patients is less than 50% after just one year.
In America, we talk about survival after five years. That gives a sense of how different outcomes look for patients in the US versus Nigeria.
Some of the differences are related to healthcare. In Nigeria, there is very little screening for colorectal cancers, particularly with colonoscopies. That means when people are finally diagnosed, the disease is advanced and more dangerous.
There is also little health insurance in Nigeria, so people can only get treatment they can pay for.
Some treatment modalities are also in very short supply. Radiation therapy, for example, is particularly important for treating rectal cancer, but there are not many facilities in Nigeria.
Your study focused on the genomic makeup of tumors in Nigeria and compared them with tumor genomics in the US. What did you find?
We found that the genetic signature in Nigerian colorectal cancers is quite different from what we’re used to seeing in colorectal cancer in North America and Western Europe.
The differences break down in two big ways.
First, nearly 30% of Nigerian colorectal patient tumors have what’s called microsatellite instability (MSI). That means there are a high number of mutations in the genes driving the colorectal cancer.
MSI occurred much more often in Nigerian patients than in American patients. MSI-high tumors sometimes can be more resistant to common chemotherapies, which can make treating these tumors more difficult.
For the other 70% of Nigerian patients, we found they did not have MSI but instead had other genetic mutations that are associated with lower survival.
For instance, many of their tumors included mutations of the cell protein KRAS. Mutations in KRAS have been called “the beating heart of cancer” because they can be so essential for cancer growth and have proven very difficult to target with drugs.
One of the main themes we’ve taken from our data is that there is a different biology at work in many colorectal patients in Nigeria compared with what we’re used to seeing in patients in the US.
Do these differences have implications for treating patients in Nigeria?
Definitely. Patients with MSI-high tumors do not respond as well to chemotherapy as patients whose tumors do not have it. So, chemotherapy that works well for patients in America might have little effect on many patients in Nigeria.
On the other hand, MSI tumors are more sensitive to immunotherapy, which are medicines that use a person’s own immune system as an ally in the fight against cancer.
Only about 10% of colorectal cancer patients in the US have MSI-high tumors in which immunotherapy could help. But three times as many patients in Nigeria have tumors that should respond well to immunotherapy — if they had access to it.
The larger point is that we must do more studies like this to learn what is effective for different population groups. We can’t just base treatment recommendations on what works for one group of people and assume it’s best for everyone.
Your study was conducted in Nigeria. Does it apply outside that country?
Based on previous cancer studies, we believe it is broadly applicable across West Africa, including large countries like Ghana. For instance, there has been a lot of work on breast cancer in West Africa and the genetic and clinical findings have proven to apply across the region.
However, that does not hold true in East Africa, where the genetic background is quite different. Again, that’s why it’s important to do research like this all over the world, so we understand what’s the same and what’s different among different populations. That helps patients everywhere.
Does your work shed any light on cancer among people of African ancestry in the US?
Black people in America are at the highest risk of colorectal cancer and suffer the worst outcomes of any group.
However, our research in West Africa does not show linkage that would explain why Black Americans suffer the highest burden from colorectal cancer.
In our study, we split out African American colorectal patients at MSK. We found that their tumors are very much like other Americans and not genetically similar to colorectal cancer patients in Nigeria.
For instance, Nigerian patients had much higher rates of MSI- and KRAS-driven tumors than the African American patients at MSK.
In future studies, we will continue to look to see if there are linkages in the African American genome to what we’re finding in West Africa.
What are your next steps?
This study lays the groundwork for a much bigger study with more patients that we’re undertaking. The aim is to confirm our genetic findings and look at risk factors for developing colorectal cancer in Nigeria, including the environment, dietary factors, and more.
We also believe there is a real opportunity to improve colorectal cancer early diagnosis programs in Nigeria. Most cancer control plans recommend using stool-based testing, but there have been no large studies evaluating how effective this method is in sub-Saharan African patients.
We are nearly done with a 2,500-patient study that will hopefully help us answer the question of the utility of stool-based testing in Nigerian patients. This is important because finding cancer earlier improves outcomes.
As we’ve shown with this relatively small study, it’s so important that we understand cancer in different populations so we can help diagnose and treat it appropriately in all patient populations. That’s what I tell people when they ask me why MSK is doing this kind of research in Nigeria.