Thomas Imperiale, MD, Research Scientist at the Regenstrief Institute and Professor of Medicine at Indiana University School of Medicine talks about the rise of colorectal cancer in young people.
Interview conducted by Ivanhoe Broadcast News in 2024.
We’ve been hearing recently that colorectal cancer rates and deaths are increasing among younger people under the age of 50. Explain that a little bit to give us some context there.
Imperiale: The phrase early-onset colorectal cancer refers to cancer being diagnosed in somebody who’s under the age of 50. It’s a gradient. When you turn 50, it’s not automatically called late onset, but for simplicity purposes, we dichotomize it at age 50. It is rising slowly and steadily, but the important thing is that the magnitude of the risk is still much lower than it is in people aged 50 and older. We don’t understand the reasons why it’s rising, but some candidate risk factors seem to turn up in repeated studies. Those include things like being sedentary, being overweight, and cigarette smoking. Family history continues to be important, but we don’t quite understand what else may be contributing. The rates have gone up quickly, so we don’t expect that this is a genetic thing. It’s not that our genome is mutating, but there may well be an interaction between genes and something in the environment, most likely diet.
How is this usually diagnosed? Are there symptoms that people might notice at home? What are things people should be looking for?
Imperiale: Colon cancer at any age is diagnosed either because of symptoms or because it’s picked up on a screening test, or it may be seen on some radiographic imaging of the abdomen. The signs are things such as rectal bleeding, a change in bowel habit, new and persistent lower abdominal pain, weight loss that is unintentional, and anemia, which is a sign that you’d see on a laboratory test during evaluation. Those are the main symptoms and signs, and people should be aware of those and should be evaluated early and not wait, especially if they notice a change in the color or consistency of their stools or if they see blood in the stool or on the toilet paper that’s new.
At what point do you know to get it checked out? How does that work?
Imperiale: You make a great point. You don’t want to overreact, but you also don’t want to underreact. I think right now, we’re more in the overreact mode. We would prefer that if people see a change in their bowel habits or they see a change in the consistency or frequency of the stool, or if they see blood and that’s new, that they just go in and report that symptom to their provider and see how their provider wants to deal with it. This is obviously going to be a decision that is made on the part of the patient and provider to decide whether, when, and how to work it up.
Explain your purpose of this study, who was involved in the study and the results and what you found out.
Imperiale: The reason we did the study was that we wanted to understand more about the risk for early onset colon cancer and what factors are associated with it. The purpose of finding those factors would be to either decide to screen people with one or more of those factors because they’re at high risk, or from a population standpoint, to get the word out about these factors so that people could maybe change their behaviors and eventually bring the population’s risk back down. That was the reason we did it. We focused on veterans because they’re mostly male, it’s more common in males and the VA has got excellent data on the patients it cares for. The combination of the high-risk population and the quality of the data is what caused us to study this population.
Then the results are these seven risk factors for males ages 45 to 49, right? Tell me what those are.
Imperiale: First, it was for veterans ages 35 to 49 because we wanted to look beyond just the people immediately close to 50. I just want to add that if you look at all early-onset colon cancer, half of it occurs in people ages 45 to 49, and the other half occurs in people who are younger than age 45. Even with these new recommendations to start screening at age 45, half of early-onset colon cancer could be missed if patients don’t get in and report symptoms. Our study started before the American Cancer Society and others revised their guidelines for when to start screening. This is why we focused on under 50. If we knew what we know now, we would probably have started at age 44. But I think there’s a message for people aged 45 to 49, because many of them aren’t getting screened, and it’s not entirely clear that they all need screening. Certainly, when I say screening, I don’t equate that with colonoscopy alone. There are other modalities and other ways to get tested for it.
What are the risk factors that you found, and what are some of the main ones?
Imperiale: We had two models; one has 15 variables in it. It performs a little bit better in terms of discriminating people with colon cancer from those who don’t have it. But the seven variable model we felt was more likely to be used in practice because it’s just easier to collect those data. It performed closely to the 15-variable model. Some of those variables included having a family history, and that’s turned up before. I want to add that what we looked at was sporadic colorectal cancer. We eliminated anyone who had a familial tendency and there are certain syndromes, certain diagnoses within families. We excluded those patients from consideration because there are already guidelines, and we know what to do with them. We looked at sporadic colorectal cancer, meaning this is new within a family. Family history was still important, having a first-degree relative or a second-degree relative increased the risk by about two and a half fold. Current alcohol use was also important. Not taking certain medications like non-steroidal anti-inflammatory drugs such as Ibuprofen, Nuprin, Advil, and Naproxen group seem to have a protective effect although we would not recommend that people start taking it to prevent colon cancer because chances are it’s going to do more harm than good in any single patient. Multivitamin use was also another factor. Age, so within that 15-year age range, being closer to 50 was a risk factor. Then an unusual variable was either not being service-connected or having a Co-pay within the VA. We think that, first, it’s unique to the VA because of the way its system is set up. But we think it’s more of a proxy for income in the higher-income veterans are less likely to be fully covered by the VA. We know that income is related, it seems like this is occurring in higher-income people that fit. Anyway, those are some of the variables that were in the seven-variable model. There were additional variables in the 15-variable model, and they included BMI. In this case, it was a low BMI. We’re treating that more as a symptom than a risk factor because other research has shown that a high BMI is a risk factor. We found that a low BMI was a risk factor, but we think that’s because people had started losing weight with the cancer diagnosis, and their BMI’s fell. If anybody’s BMI is falling and they don’t know why, that would be a reason to go in and, you know, seek care with their provider.
If someone out there falls within this age group, maybe has one or two of these risk factors, maybe is seeing some changes in their bowel movements, what should their next steps be? And then if they go to their doctor and they decide they should be screened, what options are available?
Imperiale: That’s correct, and it depends on what those risk factors are. If the patient realizes they have a first-degree relative with colon cancer, especially if that first-degree relative was under the age of 60, then colonoscopy is going to be recommended. Chances are, it’ll be recommended at the time they go in and ask for it. The recommendations say that it should be done 10 years younger than that first-degree relative. If you have a parent, let’s say who’s diagnosed at 50, then the child should have the first colonoscopy at age 40, they’re considered high risk. But for people who don’t have a high-risk family history or have one or two of these other risk factors, and especially if they’re now in the 45 to 49-year-old range, they should be getting screened anyway. The options would be to have a colonoscopy or to do a fit test, which is a noninvasive way of looking to see whether there’s blood in the stool that would not be visible to the naked eye.
Within the risk factors, are there some that were specific to the younger age group that you don’t see at all in the older age group and vice versa?
Imperiale: Yes, the risk factors we identified, most of them have been seen even in other studies of early onset colon cancer from other countries. They have been by and large in people with colon cancer older than age 50.
This study focused on veterans, but this all still applies to people who would not be a veteran, and who would not fall into that category, for the most part, other than a couple of the risk factors, right?
Imperiale: There’s not a clear reason why it wouldn’t apply to other males who are not veterans. But having said that, the proof is to take these risk factors and to look at a population of nonveterans and see how well they reproduce in terms of their discrimination.
You’re currently working on the female side as well, looking at that and if it’s similar and how that compares to females, right?
Imperiale: Along with it, but we’re publishing it separately, we have the study done, we had far fewer women, which is why we looked at the two sexes differently at different times. However, we did find risk factors in women as well. They are different than the ones in men. Some of them are the common factors to both men and women, and we have different ways of looking at these factors. We can look at them individually and then we look at them together. Looking at them together is the more powerful way to do things. But when we looked at them individually, women were more likely to be service connected. They were more likely to be cigarette smokers. They were also more likely to have a family history of colon cancer or any visceral cancer, so cancer in another organ, such as the pancreas, the uterus, the breast, or the lung. Then they were less likely to use non-steroidal anti-inflammatory drugs. So that was comparable to the men. The family history was common and the lack of NSAID use was common. Cigarette smoking, when we looked at men univariately, was a risk factor, but in our model, it fell out because other factors took it over in terms of importance. Then when we looked at a multi-varied analysis with the women, we found that being white was a risk factor. Social and economic status was protective in that not having a Co-pay seemed to be. In other words, here it was higher income that seemed to be protective. We don’t quite understand that, but that is what we found, that’s opposite from the men. Comorbidity.
Going back to your study with men, what was your main takeaway from that? Was there anything that surprised you? =
Imperiale: First, it would be that if you’re 45 to 49 years old, you should be talking to your primary care provider about getting screened for colon cancer, when to do it, and to some extent, whether to do it. Not all the guidelines agree that it needs to be done and then how to do it, should it be with a noninvasive test or colonoscopy. For people under the age of 45, you’ve got to be aware of symptoms and if you see symptoms report them promptly. If you have a family history report that and decide what needs to be done on that basis, that is the most important message. What comes after that is a little less well defined and it’s certainly not in the guidelines right now but if a person senses that they have other factors that might increase their risks such as being a big-time cigarette smoker or consumer of more or less modest amounts of alcohol, they ought to talk with their provider about getting screened and whether that would occur before the age of 45 right now, that is not the standard of care but if the family history were present, it could be the standard of care or it would be and if other symptoms are present, then I think they just need to be discussed with their provider. That’s the bottom line.
Will you briefly tell me the current screenings, and the guidelines and when that will change?
Imperiale: The first organization to come out and say we should start screening at age 45 was the American Cancer Society and when they did it, they realized that there was not high-quality evidence to support it. In other words, evidence from a clinical trial shows that it pays to start at 45 more than 50, that you tilt the balance between benefit and risk in terms of the benefit if you start at 45. They did it based on indirect data, mostly population-based data, showing that if you look at people at 45 to 49 now, they have the same risk that people 50 to 54 had 15 or 20 years ago. In some ways, 45 is the new 50 so there was that population-based data. People took those data and put them into simulation models, and they determined based on a lot of assumptions and how well the test would work in those younger folks, that there seemed to be evidence in favor of screening. That was the basis. The American Cancer Society gave it a B recommendation, meaning that there was not high-quality data but there was some evidence that it worked. Most people could expect that the benefits would outweigh the risks but not always. They started and then next to follow were the GI societies, the American College of Gastroenterology, the American Society of Gastrointestinal Endoscopy, and the American Gastroenterological Association formed a conglomerate and publishing what’s called the Multi-Society Task Force guidelines and they, too, recommended starting at age 45 and then most recently, the United States Preventive Services Task Force who are kind of the Supreme Court of screening also lowered the screening age. They all did it based on less-than-perfect data but with some realization that these rates are going up, we’re seeing more of this and perhaps we should lower the age range and see what happens. So that’s the basis. So, the guidelines say, for the most part, start at age 45 for now, average risk. If you have a high-risk family history, it depends on what that family history is, and then screens either with a colonoscopy every 10 years, the fecal immunochemical test which tests for a cult blood every year, or the test that’s color guard the combination of fit and DNA mutations every 1 to 3 years and there are other tests such as CT colonography, which is a CT scan that uses special software to reconstruct what the colon looks like. The name that’s gotten it popular is virtual colonoscopy – that’s also recommended every five years. There’s also a blood test which it’s not that good and it isn’t in the guidelines right now. There are other high-quality or what they call high sensitivity guaiac based fecal occult blood tests that are recommended every year to two years. Flexible sigmoidoscopy is recommended every five to ten years. A sigmoidoscope examines the left colon alone, colonoscopy examines the whole colon. It turns out that three-quarters of early-onset colon cancer can be seen through the sigmoidoscope because it’s on the left side. As we say in the business, it’s closer to the exit but that makes it more likely it’s going to be detected also by noninvasive methods.
END OF INTERVIEW
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