Folasade May, MD, on What's Driving Early Onset Colorectal Cancer

Dr Fola May of UCLA Health discusses her presentation at the ACG Scientific Meeting on the concerning rise in colorectal cancers among patients under 45 and some of the factors being investigated as possible contributors, from genetics and lifestyle to the larger environment.

Folasada May, MD, PhD, is is an associate professor at the David Geffen School of Medicine at UCLA and an associate director of the UCLA Kaiser Permanente Center for Health Equity. 

Early-Onset Colorectal Cancer: Screening and Symptom Recognition

• Colorectal cancer incidence and mortality have declined overall, but incidence is rising among adults younger than 50. Dr. Fola May described a birth cohort effect, and how it results in different generations having different risks of CRC. 
• Investigators are studying lifetime environmental exposures, genetic predisposition, early-life factors, and behavioral factors to identify the primary risk factors for CRC. Their relative contributions to early-onset disease are unresolved.
• Dr May urged colorectal cancer screening at age 45, or earlier with a family history, and timely evaluation of younger patients with rectal bleeding, pencil-shaped stool, or persistent diarrhea or constipation.

Hi, my name is Dr. Fola May. I am a gastroenterologist and health services researcher. I work at UCLA Health in Los Angeles where I do general gastroenterology as a practice, but spend the majority of my time running a lab that focuses on colorectal cancer prevention and early detection and screening disparities. It's been really exciting to be here at ACG.

My talk or one of my talks this year will be on what is driving early onset colorectal cancer, and I'm excited to provide a little bit of an overview of what that talk will be on. First, I really want people to walk away with understanding that we have a changing landscape of colorectal cancer. Colorectal cancer remains the second most common cause of cancer related deaths in the United States and the fourth most common cause of cancer. And the good news is that over time, we've actually seen decreasing incidents and mortality from colorectal cancer when you look at all age populations.

But the bad part of the story is that when you look at individuals who are under 50, so that subgroup of the population, we have a very different story in that we have rising rates of colorectal cancer in people under age 50. And it actually is what we describe a birth cohort effect. What a birth cohort is, is that when you look at individuals who were born in the early 1900s, for example, versus individuals who were born in the mid 1900s, versus individuals who were born in the early 2000s, their risk for colorectal cancer is very different, even just when you look at the year that you were born in. And it's not looking like that's getting any better. When we look at people who are part of Generation Z or Generation alpha, we're going to be seeing higher rates of colorectal cancer. So really this lecture is about why is that happening? Why are we suddenly seeing a disease that we described as something that happened to people in their 60s and 70s and people who are in their 30s, 40s, and 50s?

Unfortunately, the answer is that we don't exactly know. It really remains the million dollar question as to why this is happening. There are some clues that there are environmental factors that are at role here, and in particular, the impact of the exposome. Your exposome is the body of environmental factors that you have been exposed to over a lifetime. So if you could measure every exposure you've had from the environment on you over a lifetime, that's your exposome. So we think that there's a combination with exposome plus genetic predisposition for disease, plus probably somatic alterations that are happening because of the environmental exposures that's making people more likely to develop precancerous polyps and colorectal cancers.

And right now there's a lot of active research that's looking into what are these environmental exposures? Is it behavioral factors? And we've looked at alcohol, tobacco use, sedentary lifestyle, Western diet, ultra processed foods, sugar sweetened beverages. Those are some of the things that have been looked at. But in addition to looking at behavioral factors, we're also really interested to see if there's a role of early life exposure. So some of the data shows that when you look at people who were born by a cesarean section or who were breastfed or weren't breastfed, that can alter risk. That's another area that's very active in the research and also looking at environmental factors or substances that are just in the environment that we live, looking at pesticides, looking at PFAS, other chemical exposures that we might have more exposure to now or that generations that were born after the 1950s have more exposure to.

So really it is kind of a rat race in science to figure out which of these environmental factors are playing the strongest roles in leading people to develop colorectal cancer at a younger age. And I'll talk about that in my lecture and as well I'll talk about what we can do about interception.

So while we figure this science out and while we try to determine what's happening, there are things that we can do to try to better the health of our patients. So one, we can work on prevention. We can teach people about healthy diet, healthy lifestyle, and that can help drive down not only their colorectal cancer risk, but also their risk of chronic diseases and other cancers. We can also promote early and timely screening. So making sure that all of our patients at age 45 or earlier, if there's a family history, get screened for colorectal cancer. We know that screening is the number one way to decrease the likelihood of dying from this disease.

And then beyond looking at prevention and screening, we should be working on timely diagnosis. So that means that when young individuals present with symptoms that may be consistent with colorectal cancer, whether it's blood in their stool or pencil shaped stool or diarrhea or constipation that's persistent or won't go away, that we don't ignore those symptoms, that we talk to primary care doctors as well and educate them that we all need to be aware that this cancer is now something we're seeing in young people and getting those patients on a colonoscopy so we have timely diagnosis. So those are some of the interception strategies that we're using currently. And then there's ongoing science to look at whether we can use immunotherapies, precision medicine, risk models, other ways to also work towards interception of early onset colorectal cancer.

Bottom line, we want people to be aware that this cancer, the face of colorectal cancer, is different now. We want young people to be aware that they need to pay attention to their symptoms and we want their doctors to take those symptoms seriously. It's too common that I'm hearing stories about young people who've had symptoms for a year or more and they were pushed aside, are considered benign, and then we're diagnosing a late colorectal cancer that we can't cure. So we want to prevent that unfortunate story as well. And I'm hopeful that with continued research dollars and future research that we can really get to the bottom of why this is happening and how we prevent young people from dying from this disease.