Columbia Researchers Seek Answers for Rise of Colon Cancer in Younger Patients
Why has the incidence of colon cancer been rising among healthy young people? It’s one of the biggest mysteries in oncology today, and three physician-scientists at Columbia University Vagelos College of Physicians and Surgeons are hoping that a major research project they’ve launched will help solve it.
For decades, the overall rate of colon cancer has been on the decline, thanks to screening tools that can detect precancerous polyps and early cancers before they’ve spread. Two methods—colonoscopy and stool sample analysis—have proved highly effective and provide the foundation for current recommendations that everyone get screened for colon cancer starting at age 45.
Joel Gabre and Yoanna Pumpalova
But in the past two decades, epidemiologists have found that a growing number of younger people around the world are developing the disease, often not getting diagnosed until the tumors have already spread to other organs. “These reports are really consistent with what I’m seeing anecdotally in my clinic, where a lot of my patients now are younger than 45,” says Yoanna Pumpalova, MD, a medical oncologist and assistant professor of medicine at Columbia University Vagelos College of Physicians and Surgeons.
Stranger still is the lack of any obvious cause. “We know the traditional risk factors that are associated with colorectal cancer—obesity, alcohol use, smoking, consumption of red meat, and a low-fiber diet—but these factors do not explain the rise,” says Pumpalova. “Many of my young patients don’t have any of those traditional risk factors.”
Epidemiologists are now looking for other environmental factors that could explain the trend, but it’s a tough problem. “Based on our understanding of cancer biology, we suspect that these exposures were decades ago, so you’re trying to ask people to recall exposures when they were in their pre-teens to early 20s,” says Pumpalova.
Columbia surgeons Beatrice Dionigi and David Cohen obtain cells from colon cancer patients to create 3D organoids that they study in the laboratory. Photo courtesy of Beatrice Dionigi and David Cohen.
One possibility that doesn’t seem to be panning out is a genetic cause. “Many times, young patients are sent to me for genetic testing, to see if their cancer was caused by a genetic syndrome or genes strongly linked to the disease, and most of these patients are negative,” says Joel Gabre, MD, a gastroenterologist and assistant professor of medicine at VP&S. Published data back that up, showing that the majority of early-onset colorectal cancer patients don’t have known genetic risk factors. Some new immunotherapies have proved highly effective against specific genetically driven colorectal tumors, but most of the young-onset cases the Columbia team sees aren’t candidates for those drugs.
To get a better idea of what’s driving colon cancer in younger people, Gabre, Pumpalova, and Beatrice Dionigi, MD, a colorectal surgeon and assistant professor of surgery at VP&S, are taking a different approach, involving a detailed comparison between early-onset and late-onset colorectal tumors.
“We’re trying to look beyond the cancer cells themselves and also look at the cells around the tumor: Do they look different? Does that give us some clues?” says Gabre. The team is also looking at patients’ immune cells and is growing the tumor cells as organoids, complex 3D cell cultures that recapitulate many aspects of tumor growth in the colon. “We’re trying to discover in general what the difference might be and then get into mechanisms, which will then maybe lead to some insights into the cause and therapeutic opportunities,” says Gabre.
The Columbia researchers are creating organoids from the cells of patients with colon cancer to learn how the disease differs in younger and older patients. Photo: Columbia University Irving Medical Center.
The team’s preliminary data have pointed to several possible drivers of young-onset cancer, but it’s unclear how significant any of them are. “It’s going to take time to accrue enough patient samples to get these insights,” says Gabre, adding that the project is still actively seeking volunteers.
In the meantime, greater awareness of the problem could help young people get earlier diagnoses. “A healthy 40-year-old isn’t thinking ‘colon cancer’ when they have a change in bowel habits, so getting a colonoscopy or other colorectal cancer test if you have symptoms is really important,” says Pumpalova.
“I personally think that avoiding delays in diagnosis is one of the most important steps, especially in young patients," Dionigi says. "Many times young individuals are shy and do not discuss symptoms like rectal bleeding with their primary care physicians. This is the most common cause of significant delays in diagnosis." Dionigi adds that if symptoms do not subside by two months, patients should be seen by a gastroenterologist or a colorectal surgeon who may perform a colonoscopy to make the diagnosis.
Though the age of colon cancer screening was recently lowered from 50 to 45 to capture younger patients, the incidence of young-onset tumors doesn’t yet justify lowering the age further for routine screening. That could change as newer, less complex and invasive tests become available.
Pumpalova is optimistic about where the field is heading. “There’s a lot of work now developing blood-based early cancer detection assays,” says Pumpalova. “Will we have 20-year-olds doing blood tests to screen for cancer? I think it’s possible, and I think it’s something that’s likely to happen within our lifetimes.”