Chasing Life

'October is breast cancer awareness month, and that always makes me think of my mom. She was diagnosed more than 30 years ago, at a time when breast cancer carried a lot of stigma. People didn't even want to say the word cancer out loud. Thankfully, that has changed, we've come a long way with breast cancer and people are talking about cancer more openly, they are getting screened, treatments have improved. But despite these incredible advances, there is a new troubling trend. More and more young people, people in their 40s, 30s, even 20s, are being diagnosed with cancers that used to be incredibly rare at those ages. That does include breast cancer, but one of the most alarming examples is colorectal cancer. Right now, it is the second leading cause of cancer death for women under the age of 50, and it's projected to become number one in this group by 2030. It is something my guest today, Dr. Kimmie Ng, has been seeing up close. She's a gastrointestinal oncologist at Dana-Farber and started one of the first centers in the country just for young adults with colorectal cancer.

It was shocking to see that a young person, perfectly fit and healthy, no risk factors, no family history, could be diagnosed with stage four disease.

Now as a doctor, that obviously concerns me. As a dad of three daughters, it frightens me. So today we're asking the big question, why is this happening and what can we do about it? I'm Dr. Sanjay Gupta and this is Chasing Life.

Do you remember when you first started seeing younger patients in your practice?

'So I have been caring for patients with gastrointestinal malignancies at Dana-Farber for the past 20 years. And I would say in each consecutive year, my colleagues and I were seeing more and more young people coming in, no risk factors, no genetic syndrome with stage four colorectal cancer.

Wow. What was that like for you, I mean, when you first saw these patients?

'I mean, it was shocking to see that a young person, perfectly fit and healthy, no risk factors, no family history, could be diagnosed with stage four disease. And then it just became more and more common, which is also distressing. You know, it's difficult to receive a cancer diagnosis no matter what age you are, but younger people face really different challenges. 80% have children under the age of 18. They're also caring for elderly parents. They're in the midst of their careers. Some people are still getting education. Some people still planning to expand their families. And so that was part of the impetus for us starting this Young-Onset Colorectal Cancer Center to really better take care of patients and their families as they go through this experience, but also to launch that multidisciplinary research effort to really try and understand what is underlying the increase.

'Is there a particular definition of early-onset or young-onset cancer?

'So historically and in the published literature, the accepted definition is a cancer that develops under the age of 50. And I think where that 50 number comes from is, for example, for colorectal cancer, the average age of diagnosis used to be in the 70s and screening used to start at age 50. So any cancer that was developing before age 50 was considered early-onset.

So that's a movable target, it sounds like, in terms of how we define this. Are we seeing younger and younger people with these types of cancers?

Unfortunately, yes. And the most common cancer that has been talked about because it's one of the most rapidly rising in people under the age of 50 is colorectal cancer. Now, the silver lining is that if you look at patients of all ages, the incidence of coloreactal cancer and mortality from coloreectal cancer have actually been declining for decades. And that's due to successes in public health efforts to improve adherence to screening recommendations and it's due to improvements in treatments. But that benefit has not been seen in people under the age of 50, where ever since the mid 1990s, the incidence of both colon and rectal cancer has been increasing by about 2 to 3% per year in these young people. And this is happening in both men and women. It's happening all across the United States and it's actually a global phenomenon as well.

Is it all countries? Is it developed countries? What do you notice there?

'It is happening most rapidly in westernized, higher socioeconomic status countries. So for example, Australia and New Zealand have very high rates. Norway, the UK, and certain countries in Western Europe have extremely high rates of young-onset colorectal cancer.

Has the pace of that increase been changing? Has that been growing as well?

'I would say it's a fairly steady pace. So currently, young-onset colorectal cancer is already the leading cause of cancer-related death in men under the age of 50. And the steady increase will mean that by the year 2030, it will also become the leading cause in women. Right now, it is the second leading cause for cancer death in young women trailing behind breast cancer. But again, if these increases and this rate continues, it will surpass breast cancer to become the leading cause in women as well.

I guess the obvious question is why?

So that is the big question of the decade. I think it is what so many of us researchers are trying to understand. So we do have some clues. If you look at the epidemiologic trends, you'll notice they follow what we call a birth cohort effect, where the increasing incidence follows generations and varies by generations. And to illustrate that point further, if you take a person born in 1990, they now have quadrupled the risk of developing rectal cancer and over doubled the risk of developing colon cancer compared to a similarly aged person who was born in 1950. Now that's quite dramatic. And when we see these birth cohort effects, what it usually suggests is that there's some recent environmental exposure or exposures that have happened recently that are contributing to that rise. And we do know that things like colorectal cancer and other gastrointestinal cancers are increasing the most rapidly in young people. So the big question now is what are these things that are actually leading to this increasing incidence in young.

There must be something in the environment then. Obviously our genetics did not change that much in 30 years to suddenly make us more likely to develop these cancers. So can you sort of connect the dots then? If it's diet, if it's some sort of toxic exposure, how does that lead to increased cancer rates?

So, I want to just highlight something important that you said, which is that we don't think this is any shift or change in human genetics, right? These increases have happened too rapidly for that to be the case. However, the younger you are when you're diagnosed with cancer, the higher the chance of finding a genetic syndrome or predisposition. So it is a key takeaway that every young person diagnosed with cancers should have germline or hereditary genetic testing. To make sure that one of these genetic syndromes is not in place.

'So how has that changed your practice then? If you're seeing more and more patients coming into your office with early-onset cancer, are you genetically testing the majority of them now?

'We are. And that was one of the goals when we started our Young-Onset Colorectal Cancer Center. And so we have made that reflexive. So automatically, when somebody has a new patient appointment here and is seen, they are referred and booked automatically for a genetics appointment to meet with a genetic counselor and then to learn about genetic testing and then sign and form consent for that to happen. So we've now automated it to be sure that we are reaching almost every single young-onset colorectal cancer patient and making sure they're getting that testing or at least learning about it. But to your point, we do have some clues through prospective cohort studies that we've been involved in about what some of these dietary and lifestyle factors may be that increase the risk of developing young-onset Colorectel cancer. Now, the leading hypothesis has been obesity. As we all know, obesity rates have been skyrocketing in recent decades that seems to have paralleled the rise in these young-onset cancers and colorectal cancer and gastrointestinal cancers, which are rising most rapidly, are known to be strongly linked to obesity, no matter what age you are when you're diagnosed.

Talk me through it, so someone who carries too much weight, they're obese. How is that linked or associated with colorectal cancer?

In a state of obesity, there is increased inflammation in the body, and we do know that inflammation is a precursor and can lead to the development of so many different types of cancers. Inflammation leads to precancerous changes that then eventually become invasive cancers. Growth factor signaling and hormone signaling is altered when there is a state obesity. And then finally, we also do suspect that obesity can affect the composition and diversity of a patient's microbiome.

So it may not necessarily be the body weight itself as much as it is all the things that come with that, the increased inflammation, the changes in microbiome and things like that.

'That's right, and I think that the same can be said for a variety of other diet and lifestyle factors. These include things like sedentary behavior, intake of sugar-sweetened beverages, higher intake of what we call a Western pattern diet, which is basically diets high in red meats and processed foods and sugars. All of these dietary and lifestyle factors have been linked to an increased risk of young-onset colorectal cancer. However, I have to really emphasize that my colleagues and I, when we're seeing young patients coming into our doors with this diagnosis, most of them are not obese. You know, many are marathon runners, they're triathletes, they're eating really healthy, they eat organic, and yet they're still being diagnosed with young-onset colorectal cancer.

Yeah, it is interesting that these young people come in and oftentimes they're super fit. It's not genetics. It doesn't appear to be the obvious environmental influences like obesity and sedentary lifestyle. So what is, what is going on?

It is really a mystery. And I think part of the issue may be that it could be early life factors that are actually at play. And if you think about it, somebody coming into your clinic with this diagnosis, if you ask them, what were you eating at age six? How much physical activity were you getting when you were seven years old? It's really hard to remember. You know, in an ideal world, we would study people from in utero to infancy through childhood, through adolescence, through young adulthood, every few years, collect all kinds of samples like stool samples, benign biopsies, blood samples, collect their diet history, collect their physical activity history, their environmental exposures, home environment, and then follow them until they receive a diagnosis of cancer. And then you would really be able to understand what factor it was and at what period of your life mattered to lead to that diagnosis. But a study like that is really not feasible. It would take too long, it would be too expensive, so we need to come up with other ways to try to answer this question.

So it sounds like you're saying even if you are very fit at the time of diagnosis, how you lived your life, even as a very young person before you're 10 years old, might play a role here in a future diagnosis.

Yes, and it could be things that have affected, for example, your microbiome in the first decade of life. There was just a paper published in Nature that showed three times more prevalence of a mutational signature, which is a classic pattern of changes in your DNA, caused by a genotoxin called colibactin. And this colibactin is produced by a microorganism called PKS positive E. Coli. So if this bug is in your microbiome in the first decade of life producing this genotoxin that can damage your DNA or change your DNA in a characteristic way that may lead to increased susceptibility for cancer at a younger age. That is what we have to figure out. What is happening early in life? What are the dietary environmental exposures that led to that, that is actually causing this rise in young onset cancer.

'If you think about carrying too much body weight, having obesity, inflammation, microbiome, that seems like a body-wide sort of phenomenon. Are other cancers then increasing as well? Why so much focus on colorectal cancer?

In fact, yes, this group of digestive system organ cancers, so things like pancreatic cancer, things like endometrial cancer, which have known and strong links to obesity are both increasing as well in young people under the age of 50.

I hear that you're saying obesity and the microbiome and inflammation, probably high on the list, but how confident are we that that's really what's driving this?

I don't think we are confident yet. These are individual studies. They're observational in nature. They show associations, but not necessarily causation. They're not showing cause and effect yet. And that's where I do think there will be more laboratory studies, for example. And we are still in our infancy in understanding whether those are true risk factors, whether there is a link, and actually how do they actually lead to cancer in terms of these biological mechanisms.

Is that important for you to know as an oncologist, the why behind the what? Like why is this happening? Or is it just important to sort of focus on what you do about it?

'I think they're both important, knowing why and what the exact risk factors are for an individual will allow us to be able to implement precision prevention, where we are tailoring prevention strategies and screening strategies based on an individual's risk profile. I do think that's where we need to head because I think it's highly unlikely, for example, that the screening age for colorectal cancer is going to be lowered any further than age 45, at least for a while. But it's also very important to know how to treat this. And right now, because we haven't necessarily pinpointed consistent biological differences between the cancers that happen in younger people compared to the cancers that happen and older people, a 30-year-old right now is treated exactly the same according to medical guidelines as somebody who is in their 70s. You would expect that a young person With fewer comorbidities, better performance status would have a longer survival. But that's not necessarily true, actually. And a lot of studies have showed that the youngest patients actually seem to have shorter survival compared to an older patient.

Why not start screening younger?

'So I think we need to keep in mind that although there are rapidly increasing rates of these cancers in young people, the absolute number is still quite small. And it is still relatively rare to develop any of these cancer at a really young age. And so, so many different factors have to go in to what allows a successful screening program to be implemented and the cost effectiveness. There are risks to screening as well. And so when you consider all of these factors in modeling studies, you know, the U.S. Preventive Services Task Force found that it made sense to decrease the age from 50 to 45, but lowering it any further, where the absolute numbers do get relatively small, probably doesn't make sense right now. And so I think the field needs to head in the direction of figuring out why this is happening, what are the risk factors, who is at risk, and can we tailor that high-risk 30-year-old for earlier screening.

Coming up, what symptoms should you actually be looking out for? And Dr. Kimmie Ng shares the gold standard recommendations for screening. That's after the break.

I've been a reporter for 25 years, you know, and I think this is one of the most challenging things, this idea that I feel fine, there's nothing wrong with me, I'm going to do something preventative for my health, but I'm not even sure what the benefit is ultimately from doing that. Eat right and exercise and nothing will happen to you. It's not the most inspiring message, right? How do you make the case then for people to get screened and in your patient population, and perhaps even get screened earlier?

Actually, the data show just getting one colonoscopy can significantly decrease your lifetime risk of developing colorectal cancer afterwards. It is much better to undergo the prep and get that procedure than to receive a diagnosis of coloreactal cancer and then need surgery and chemotherapy and radiation, right? So if you think of it like that, screening is nothing compared to actually having to undergo treatment for a cancer.

Do you have any idea what the percentage of people who should be screened at age 45 are actually getting screened?

So the latest data show that still only about 25% of people between the ages of 45 to 49 are being screened.

Wow.

'And in the older population, it's been long that screening was the recommendation to start at age 50. Only 66% of the people over the age of 50 are getting screened, you know, there was this effort to get 80% of the population screened in the United States, but we haven't yet reached that goal. And so it is really important that we continue public health efforts to really advocate that screening can be life-saving and it really needs to be done.

Is this the stigma again, do you think? I mean, you know, my mom had breast cancer and this was over 30 years ago. This was in the early 90s. And I remember the first time I sort of brought it up at a gathering with people. I'm a doctor. This is something that I obviously we went through as a family, but she did not wanna talk about it. I feel like the stigma around breast cancer was pretty significant. And I think it has declined now. Women are much more likely to be open about it, talk about their experience, their treatment, their survival. Are we where we were with breast cancer 30 years ago with colon cancer now?

'I do think we are. There are so many different reasons why people feel uncomfortable talking about anything related to their bowels or their stool. And there are cultural differences in this stigma as well. And, there are gender differences where women may feel more uncomfortable talking about that part of their body than men, for example. And so, some of the things we've been trying to do are to work with advocacy organizations to get out into the communities, go to church communities, really try to advocate and talk about colorectal cancer, the symptoms, make people aware of what they are, and the importance of screening. There are significant disparities by race and ethnicity in the rates of coloreactal cancer as well as death from coloreectal cancer where minority populations such as non-Hispanic blacks have 20% higher incidence of developing colorector cancer. And when they get it, it's at a younger age and a 40% higher mortality from colorectal cancer compared to the non-Hispanic white population. And part of that is due to disparities in uptake of screening. So it's really important to get out into every community and advocate for the life-saving potential of screening.

Is there anything that you recommend different than for someone who may be listening, who is in their 30s or 40s, who's worried about this? They hear colorectal cancer rates are going up. We're not entirely sure why, but that's happening. Eating right, exercising, doing all the things that you should do regardless, that's already on their radar. Is there something else they should be doing?

Yes, I think knowing the symptoms, the red flag symptoms that may be associated with colorectal cancer is really important. And for young people, most of these cancers arise in the left side of the colon or the rectum. And so the most predominant presenting symptom is seeing blood in the stool. For example, if you see blood that's actually mixed into the stool rather than sitting on top of it or in the toilet bowl or just on the toilet paper. If it's mixed in the stool, that's perhaps a little bit more concerning and a little more characteristic of a malignant cause. Other common presenting symptoms include a change in your bowel habits, so new diarrhea, new constipation that's different from your baseline, a thinner caliber of your stools, abdominal pain, there could be fatigue or shortness of breath with exertion that could indicate anemia or low red blood counts. And then unintentional weight loss is another red flag symptom that may indicate a diagnosis of colorectal cancer. I think part of the problem that's stifling conversation about this disease is that nobody is comfortable talking about their stool or seeing blood in their stool such that they don't maybe even mention this to their primary care doctors or their family members. But it's so important that we try to normalize these conversations and ask physicians to routinely and systematically ask are you having blood in the stool? Are you have a change in your bowel habits so that these symptoms can come to light?

By the way, it's very interesting because I was turning 46 and I thought I had four more years before I needed to get a colonoscopy and then the guidelines changed on me. So I was good about it and went ahead and got that and luckily everything looked good according to my gastroenterologist. But can you just tell us what is the current gold standard recommendations for screening then? If somebody's listening and thinking, hey, look, I should pay attention to this, what would you tell them?

'Yes, and what I always say is the best screening test is the one that actually gets done. So everybody at average risk for colorectal cancer should start their colorector cancer screening at age 45. And this screening can include things like colonoscopy, but it can also be things like stool-based tests that you can actually do at home. You get a kit in the mail, you collect your stool at home and you send it back through the mail. And those are also acceptable screening tests that are great for early detection of colorectal cancer, compared to a colonoscopy, they're almost just as good for early detection. I think the differences are the stool-based tests are maybe not as good for prevention, right? They're not as at picking things up at the polyp stage. Whereas if you're getting a colonoscopy, you're in there. If you see a polyp, you can take it out, you can remove it and prevent that cancer completely from occurring. By the way, CT colonography or virtual colonoscopy is potentially another way of doing colorectal cancer screening, but through doing a CT scan of your colon. So many different methods of screening, average risk individuals should start at age 45 with any one of these methods. And it's also really important to talk to your family about a family history of coloreactal cancer or a family history of an advanced polyp even. Because if that family history exists a patient may actually qualify for screening at an earlier age than 45, and that could potentially be life-saving as well.

And then how often after 45?

'So it depends on what the findings are. So if your colonoscopy is completely clean, you're good for 10 years. You don't need another exam for 10 years. For stool-based tests, they have to be done a little bit more frequently. So for things like a FIT test, that has to be yearly. Things like Coligard, which incorporates some molecular changes into the detection and stool, can be done every three years, for example.

I'm curious, do you have children?

I have two girls, ages 17 and 13.

I have three girls, 20, 18 and 16, so similar phases of life. Do you recommend anything different for your kids to maybe try and prevent these types of cancers?

Yes, I mean, even though a lot of patients who come in our doors do live healthy lifestyles and are not obese, these factors still do matter, and especially early on in life. And so it really is important to focus on promoting a healthy lifestyle, an active lifestyle, eating a healthy diet, not smoking, not drinking early in life, and I really emphasize to my own children and my family, to be open and honest about what might be happening and what symptoms they might be experiencing, and they are, and I think that's so important, that awareness and that lack of hesitation to talk about symptoms that may be uncomfortable to talk about.

It may feel awkward, but we do need to normalize those conversations. So I appreciate you helping us do that. Thank you so much for your time.

Thank you so much for having me.

'That was Dr. Kimmie Ng, a gastrointestinal oncologist at Dana-Farber Cancer Institute, professor of medicine at Harvard Medical School, and founding director of the Young-Onset Colorectal Cancer Center. For more information and resources, check out their website. We'll link to it in the show notes as well. Thanks so much for listening.