Kimmie Ng: Somebody who is born in 1990 now has quadruple the risk of developing colorectal cancer and over double the risk of developing colon cancer compared to a similarly aged person who was born in 1950.

Samantha Laine Perfas: Contrary to overall cancer trends, there’s been an increase in certain cancer diagnoses in people under 50. From 2010 through 2019, the incidence of 14 cancer types increased among people in this demographic. The big question is, why? Does it have to do with lifestyle choices? Are there environmental factors at play? What can be done to mitigate risk?

Welcome to “Harvard Thinking,” a podcast where the life of the mind meets everyday life. Today I’m joined by:

Timothy Rebbeck: Tim Rebbeck. I’m the Vincent Gregory Professor of Cancer Prevention at the Harvard Chan School and the Dana-Farber Cancer Institute.

Laine Perfas: He’s a cancer epidemiologist and studies global cancer trends and disparities. Then:

Ng: Kimmie Ng. I’m an associate professor of medicine at Harvard Medical School.

Laine Perfas: She’s also a medical oncologist at Dana-Farber Cancer Institute and the founding director of the Young-Onset Colorectal Cancer Center. And our final guest:

Tomotaka Ugai: My name is Tomotaka Ugai, I’m a cancer epidemiologist at Harvard T.H. Chan School of Public Health.

Laine Perfas: Tomo is also an instructor at Brigham and Women’s Hospital and a founder of the International Cancer Spectrum Consortium.

And I’m Samantha Laine Perfas, your host and a writer for The Harvard Gazette. Today we’ll look at early-onset cancer and how younger people can navigate their increased risk.

I think it’s important to start with the context of cancer overall, which is that rates have been declining in recent years. However, some cancers are on the rise, specifically in people under 50. What are we seeing?

Ugai: I think when we talk about increase in early-onset cancer, this is not a simple story. The incidence of early-onset cancer has been increasing in many parts of the world, but this is different between cancer types, regions, and countries. So we need to know more about such differences. Our recent analysis shows that many early-onset cancer types, including colorectal cancer, breast cancer, uterine cancer, kidney cancer, pancreatic cancer, and multiple myeloma have increased more rapidly compared to late-onset cancer types. Also for colorectal cancer and uterine cancer, both the incidence and mortality have increased concurrently. And this phenomenon is mainly observed in high socioeconomic countries, including the United States, the U.K., Australia, and New Zealand.

Rebbeck: If I could just add to what Tomo said, I think one of the very interesting observations that he raised is that what we’ve been observing over the last couple of decades is increases in cancers diagnosed under the age of 50, at many different tumor sites, around the world, in men and women. And it’s a phenomenon that we’ve barely ever seen in the past. The last time we saw this kind of phenomenon on a global scale and with such changes was lung cancer in the mid-20th century, when it started rising from almost a rare cancer to the most common cancer. But we figured that out pretty quickly; that was cigarette smoking. In this case, we’re talking about probably major exposures or something like that, but we’re also talking about many cancers all over the world. And so there’s something really critical and interesting going on here.

Ng: And what’s interesting is if you look closely at the epidemiologic trends, they follow what we call a birth cohort effect, where the increase is really varying by generation. To give you an example for colorectal cancer, somebody who is born in 1990 now has quadruple the risk of developing colorectal cancer and over double the risk of developing colon cancer compared to a similarly aged person who was born in 1950. And this is important because it gives us clues as to what might be underlying the rising trends And what a birth cohort effect usually suggests is that it’s a combination of some environmental exposures that are affecting the incidence by generation.

Laine Perfas: Kimmie, could you tell me a little bit more about the birth cohort effect, and also what’s it been like treating patients who are now developing these cancers at a much younger age?

Ng: If you look at the trends, the rise has been happening in every birth cohort basically since 1950. But the trends have been formally documented in published literature since probably the mid-1990s. So for colorectal cancer, for example, we have been seeing about a two percent per year rise in the rates of colorectal cancer in both men and women since the mid-1990s, and it is estimated that by the year 2030, colorectal cancer will be the leading cause of cancer-related death in people under the age of 50.

It is well-known that the challenges faced by younger people diagnosed with cancer are very different than the challenges faced by older people. And that was partly the impetus for us starting our dedicated Young-Onset Colorectal Cancer Center so that we can better address these unique issues that affect young people and that ranges from issues about fertility — many of these people are still trying to expand their families or start their families. It extends to sexual health. It extends to career and education disruptions, and over 80 percent of young patients with colorectal cancer have children under the age of 18 when they’re often diagnosed with an advanced stage of disease. Many are also in the sandwich generation when they’re taking care of elderly parents as well. It’s just such a difficult time to be hit with a terminal cancer diagnosis. And so there are high levels of psychosocial distress. Many need social work support and psychiatric support, so we are trying to provide them with all of that through our center.

Laine Perfas: It’s interesting that the last time a phenomenon like this happened it was with lung cancer. It was then directly linked to smoking cigarettes. Do we have any sense of what might be contributing to the current trends?

Rebbeck: We certainly have many hypotheses that make sense. Many of those of course, include diet, lifestyle, obesity, alcohol, and tobacco use. So major exposures, so they would have to be fairly common exposures in order to see the rate changes that we’re observing. They would have to be fairly general carcinogen exposures, meaning they would have to be influencing cancers at multiple sites. Because that’s what we’re seeing. They would have to be acting in men and women since that’s what we’re seeing in the epidemiological data. And they would have to be things that have probably been changing over the past decades worldwide. And so you can imagine what some of those are. I’m sure we’ll hear more from Tomo and Kimmie about this and some of the work they’ve done. But obesity fits that pattern very well. Obesity is something that has increased in recent decades substantially. it’s changed across the world. It’s happening in men and women, particularly it’s happening in children. If to the degree that obesity is a leading explanation for these changes, it’s probably happening earlier in life and children. And the lag that we’re seeing between changes in the exposure and the advent of the earlier-onset cancers is probably happening in a lag that started earlier in life, obviously early-onset cancers. And so all of those pieces fit, I’m guessing it’s not the only explanation. And there are many other hypotheses out there that you can guess, microplastics, or like you can begin to think about all the things that might be going on that have changed in recent decades.

Ugai: I think there are several important clues for potential causes for the increase in early-onset cancers. First, as Kimmie mentioned, there is a birth cohort effect, which means that more recent generations have a higher risk of early-onset cancers; this effect is linked to the change in environmental factors or lifestyle factors for many years. For example, many lifestyle factors such as obesity, physical inactivity, diet, and some environmental factors such as air pollution have changed since 1940 to 1950, which may be a very important factor.

Second, as I mentioned, several early-onset cancer types have increased more rapidly compared to later-onset cancers. This suggests that certain exposures, such as new risk factors or established risk factors, have shifted toward younger populations. For example, the prevalence of obesity has increased among younger populations but also pollutions or microenvironments or some other toxins can be considered potential new risk factors for early-onset cancers.

Ng: Just to follow up on this discussion about obesity, I agree it has been posited as the leading hypothesis for why early-onset cancers have been rising globally. And indeed, if you look at the cancer types that have been increasing in young people, they are all known to be associated with obesity, including uterine cancer and cancers of the digestive system, which don’t only include colorectal cancer, but also pancreatic cancer, biliary tract cancer, appendix cancers, and so many different others. However, I can tell you that in our clinics here at Dana-Farber, the patients we’re seeing for the most part are not obese and they live healthy and active lifestyles. They eat very healthily. So I do think while obesity is certainly a contributor to the rising trends, it is probably not the only answer.

Laine Perfas: There are actually people in my life who are very young and active and healthy who are shocked to find out that they have cancer and they’re not always easily treatable, some of them are very aggressive. Thinking about the trends, it’s hard not to be like, I was born in the ’90s, is that just a reality that my generation is facing, that my rates are going to be four times higher than someone born in the 1950s regardless of my choices? Do we have more agency than that?

Ng: I will say that following a healthy diet and lifestyle and maintaining a normal body weight is still so critically important. And I think Tim was mentioning these factors and behaviors in early life are what we think are the important time window of exposure that leads to increased susceptibility to these cancers in young adulthood.

So I do still think it is really important for public health agencies and the health system in general to educate children, adolescents on the importance of a healthy diet and lifestyle and on maintaining a normal body weight. Because those things will likely not only protect you against developing multiple different cancers at whatever age, but also against a host of other chronic diseases.

Rebbeck: The other point I’d add to that is, depending on how you hear this message as a person born in the ’80s, ’90s, I could imagine people panicking about that. And I think it’s important to keep in perspective that most of these cancers are still predominantly diagnosed in older individuals over the age of 50. It’s not like individuals under the age of 50, age 40 are now the main people diagnosed with these cancers. That’s not the case. It’s certainly true that we have a much, much higher risk of cancer now than we did earlier if you’re under the age of 50. But it is still relatively rare.

Ugai: I just want to follow up with Kimmie’s very important point about early-life exposures. Evidence indicates that early-life healthy diet is associated with reduced risk of early-onset colorectal cancer. So if you’re parents, you can start healthy diets or healthy lifestyle as soon as possible. At the same time, you can teach such healthy lifestyles to children so that children can have reduced risk.

Laine Perfas: We can adopt healthier habits, but I also want to talk about genetics, something we can’t change. What role do genetics play?

Rebbeck: It’s well-known that individuals who have an inherited predisposition to cancer tend to be diagnosed at a younger age. So individuals who are diagnosed with hereditary breast cancer because they’ve inherited a BRCA1 or BRCA2 mutation, the average age of breast cancer diagnosis, for example, is 10 years younger than the general population. Genetics, and particularly these high-penetrance hereditary patterns of cancer, are certainly associated with the early ages of onset. But what we don’t see or don’t anticipate is that changes in the germline genetic pattern that create these very high risks have changed substantially over the last decades. We don’t expect that germline genetics, frequencies, mutation types or whatever have changed so much that it would explain the majority of these early-onset diagnosis differences that we’ve observed. Having said that, cancer is a genetic disease. There’s always underlying susceptibility to cancer. And it’s possible and perhaps even likely that there are gene-environment interactions that people who have an underlying susceptibility and now are being exposed to whatever the major factors are, that they’re becoming penetrant. They’re becoming diagnosed earlier and earlier because of those interactions between genes and environments.

Ng: This is such an important topic because, I completely agree, if you look at gastrointestinal cancers and those that are happening in people under the age of 50, probably up to a quarter or so are found to have a hereditary reason for having developed that cancer at a young age. But that leaves 75 percent having sporadic cancers not related to family history or a hereditary predisposition, but because you are much more likely to identify a hereditary condition the younger you are diagnosed, it is important that the standard of care includes hereditary genetic testing for any young person under the age of 50 who is diagnosed with cancer.

Laine Perfas: I’m curious to hear what you all think about the lowering of screening ages for various cancers. For example, colorectal cancer was lowered from 50 to 45. Breast cancer screening has actually fluctuated multiple times. What are the pros and cons of screening earlier?

Ugai: As you said, in 2018, the American Cancer Society recommended initiating colorectal cancer screening at the age of 45 instead of age 50 in the average-risk populations. I personally think that this approach would work. But at the same time, we need to think more about cost-effectiveness, invasiveness, and potential complications. Yeah, this is a little bit difficult to decide.

Rebbeck: To Tomo’s point also because cancers are rarer in earlier ages, lowering the age of screening is inherently less efficient, if you will. We’ll detect fewer cancers if we screen the same number of people because they’re just rarer. And so the notion of changing cancer screening ages for those that we can screen in this situation, colorectal, breast, for example, the approaches probably pay off a little bit less. What are the risks and trade-offs and cost benefits? And I think that’s really an important consideration for our public health.

Ng: I do think that lowering the screening age for average-risk individuals for colorectal cancer down to 45 is a good first step in the right direction. The majority of young-onset colorectal cancers are diagnosed in people in their 40s. However, going back again to those epidemiologic trends, the rates of rise are actually steepest in the very youngest patients who are below the eligible age of screening. And so clearly lowering the age or basing screening recommendations on chronological age alone is going to be insufficient for addressing this problem of early-onset cancers. And what I think this means is that it really highlights the importance of doing the research to better understand, what exactly are the risk factors? Who is at risk? What are the causes? And then, can we identify the young people who are at higher risk of colorectal cancer and target them for earlier screening?

Rebbeck: I think that’s really important, because we’ve seen that population-based screening has value in many situations, but risk-adaptive screening approaches are becoming more and more relevant and appropriate, and particularly in this situation. So for example, not only in breast cancer do we think about different ways of screening, like we would use MRI in very young women, not mammography, for example, but the timing of those, the cadence of that screening. So as we start talking about more unusual individuals, because of their risk, and in a rarer situation like colorectal cancer in the 30s, a population-wide screening, it becomes less and less compelling, and a targeted screening kind of approach or targeted early detection is probably what we need to be thinking more and more about.

Laine Perfas: Have screening changes made a difference or is it still too early to tell?

Ng: There actually was just a recent paper published in JAMA this month that did show that the uptake of colorectal cancer screening in people between the ages of 45 and 49 has been slowly picking up since the United States Preventive Services Task Force issued their revised guidelines to lower the age. And actually, there does seem to be a promising shift toward detecting more early-stage cancers now because of the recent guideline change. So I think it is starting to work. It is still early days, but I do hope the uptake will continue.

Rebbeck: And I think one of the interesting observations is that most of the cancers that we’re talking about don’t have screening modalities. Colorectal cancer is clearly the 500-pound gorilla of this conversation, in part because it’s a common cancer, but it also has very clear, actionable things you can do, like colonoscopy. Most of these other cancers don’t. And I think that screening is critically important, but we can’t do that for pancreatic cancer or kidney cancer or whatever. And so there’s a lot of other issues that we need to think about beyond screening for most of these cancers.

Ugai: Also I would like to add one more important thing about early-onset cancer and screening. So the increase in early-onset cancer can be probably partially attributable to increasing screening and early detection. And also, advances in a cancer registry system or screening devices can also affect the increasing incidence of early-onset cancers. Again, it’s important to better understand what’s going on at the global scale.

Laine Perfas: Are you saying it’s possible that the increase in rates is partially due to simply an increase in screening, that the cancers may have been there before, we just didn’t know about them because we weren’t screening for them?

Ugai: Yes, that’s true, and for example, for thyroid cancer and prostate cancers, when we looked at the actual data, the incidence of early-onset prostate cancer and thyroid cancer has been increasing for the past few decades. But when we looked at both incidence and mortality, the mortality has not increased. So potentially, this increase might not be true and this is attributable to increasing screening.

Ng: I just want to point out though that is not true for colorectal cancer, right? The rise has been documented since the mid-1990s when screening age was 50, and most of the cases of young-onset colorectal cancer are late-stage cancer, Stage 3 or 4, both points of which really rule out this rise as being a screening effect.

Rebbeck: It’s very true. There’s a great example in South Korea a couple decades ago where they started screening for thyroid cancer and the rates skyrocketed. The mortality rates stayed exactly the same, because there’s a lot of thyroid cancer in the population that’s indolent and doesn’t cause any problems. Similarly, as Tomo was saying, with prostate cancer, lots of indolent prostate cancer. I’m not sure that’s the case with colorectal cancer, that there isn’t a lot of indolent colorectal cancer that just sits there for many decades and doesn’t progress. So I think each cancer is going to be different. Each cancer probably needs to be thought of in terms of screening and in terms of overdiagnosis, and the value of screening. They’re all going to be quite different.

Just as a note for prostate cancer, which I think is a great sort of canary in the coal mine for the kind of things that we anticipate happening in cancer screening. The U.S. Preventive Services Task Force changed its guidelines about prostate cancer screening with PSA over many years. And in the most recent change that happened about 2018, when they started slowing down that screening, in more recent periods — last few years — now the mortality in prostate cancer is starting to rise. That took a long time to have happen, and it’s not an early-onset cancer by any means, but I think that when we see these very broad changes in policy and guidelines, if the screening is making a difference, we will eventually see changes to mortality.

Ng: Yeah, it’s so important to consider the individual screening practices of each country as you compare global trends in early-onset cancer incidence. As an example, in Japan and South Korea, there is population-based and opportunistic screening for gastric cancer. And so the rates of gastric cancer have actually not been rising in young people or older people in those countries. It’s really important to take into consideration what different countries do when interpreting incidence trends.

Laine Perfas: It is pretty well-known that early detection is a key to better, more effective treatment. Beyond just screening, what barriers stand in the way to earlier detection?

Rebbeck: In colorectal cancer, of course, it’s the ability and willingness for people to have a colonoscopy. And Kimmie can probably talk a lot about this from her experience, but colonoscopies, while very effective, are things nobody likes. It’s hard to do. It’s icky. It’s not something that is an easy thing. And there are some clear barriers there. And I’d be interested to hear the others’ opinions about a tiered approach where we use fecal occult blood or FIT testing or something like that as an adjunct to a colonoscopy. Are there better approaches that might maximize the ability to detect cancers even among people who may be resistant to doing the gold standard colonoscopy?

Ng: On top of personal reasons why somebody would not want to get a colonoscopy, there are also other logistical barriers, right? Especially for people who have to work multiple jobs and cannot take time off from work to do the bowel prep and then find a ride to their colonoscopy and find a ride home from their colonoscopy. These are real challenges that many people face on a daily basis that really prevent them from being able to do screening. And so I think that is why it’s so important that the United States Preventive Services Task Force included a menu of different test options as ways to screen for colorectal cancer. Because a home-based stool test may be much easier for somebody to do than overcoming all those logistics to get to their colonoscopy.

Ugai: In addition to that, I just want to highlight the importance of increasing awareness of early-onset cancers. Maybe we can speak up more, but also we can collaborate with industries or policymakers to increase awareness of early-onset cancers.

Rebbeck: And I would add to that list clinicians, primary care clinicians, people who might be the first line in identifying people who might have symptoms of colorectal cancer but the patient is 30 years old and they don’t think about it, or they put it off as something else. So I think there’s a lot of awareness on lots of different levels to ensure we get people into the right care pathways at the earliest possible time.

Ng: I also think there is a stigma around certain cancers that prevents conversations about the diagnosis, about the symptoms. Patients are not comfortable bringing up symptoms related to their bowels to their primary care physicians or even raising them to their family members. And so I do think normalizing conversations around some of these issues will also go a long way in raising awareness.

Laine Perfas: There is still so much that we don’t know. What should we be researching or where should we be looking next for answers?

Rebbeck: The generic answer to that is to understand what the lifestyle, obesity, adiposity, environmental exposures are likely to be. And we have a lot of clues already from studies, but those studies are very difficult to do and they require very large sample sizes done appropriately. They may require prospective cohorts that may take years or decades to follow. And the gold standard of identifying these kinds of risk factors is something that we won’t have an answer for immediately.

Ng: This is such a challenging problem to study, and the life course studies are probably the best way to understand what’s happening in childhood that then changes you somehow to make you at increased risk of developing cancer in young adulthood. But those take too long, would be too costly. And we really can’t wait that long for answers, honestly. Because of how complex this phenomenon is, it really is going to take a multidisciplinary team. We need epidemiologists. We need oncologists, basic scientists, environmental health experts all working together to really try to understand what the underlying etiologies are.

Rebbeck: And there may be a great opportunity for a quick turnaround of basic science. Basic science can happen a lot more quickly than these large epidemiological studies. And if we really had a good sense of what the molecular etiology, the mechanism of early-onset cancers is, is it different than later-onset cancers? Are the molecular signatures in those tumors different?

Ng: To give an example, actually, there was a recent paper published in Nature that identified a mutational signature in DNA caused by a genotoxin called colibactin that seems to be a lot more common in younger people who develop colorectal cancer than older people who develop colorectal cancer. And it’s exciting because it’s the first evidence that the microbiome, because we think a bug called pks+ E. coli is producing this colibactin to damage DNA, may be the contributor. It’s not going to explain all of early-onset colorectal cancer, but it does implicate potentially the microbiome as a reason for why this might be happening worldwide.

Laine Perfas: What advice do you have to empower our listeners to better manage their health and mitigate their cancer risk?

Rebbeck: Awareness. Understand the symptoms of some of these cancers and ask questions. Become educated, and not only about colorectal cancer, but many of these early-onset cancers in individuals who are under the age of 50. And, as Kimmie said earlier, live a healthy lifestyle: Eat well, exercise, keep your weight down, all the things that we know from all of the other advice we’ve gotten around cancer and other diseases. Those are certainly things that are empowering. People can do those; none of them are easy, but people can do them to minimize their risks.

Ng: I would also say for the cancers that do have screening guidelines and programs, get screened, because that could be lifesaving. And something else that’s important to mention is to know your family history too, because if there is a family history of that cancer in your relatives, especially if it happened at a young age in those relatives, then you can qualify to get screened at an earlier age, and that as well can be lifesaving.

Ugai: The important thing is healthy lifestyle and healthy diet. The important fact is that many established cancer risk factors overlap between early-onset and regular-onset cancer. So if you can avoid established cancer risk factors, you can reduce the risk of other non-communicable disease. Early life exposure can be very important, so you can avoid such cancer risk factors as soon as possible. At the same time, you can teach such a beneficial, healthy lifestyle to younger populations. I think that’s important.

Laine Perfas: Thank you all for taking time to talk to me today about this.

Rebbeck: Thank you for having us.

Ng: Thank you for having us.

Laine Perfas: Thanks for listening. If you’d like to see a transcript of this episode or listen to our other episodes, visit harvard.edu/thinking. To support us, rate us on Apple Podcasts and Spotify, or share this episode with a friend or colleague. This episode was hosted and produced by me, Samantha Laine Perfas, with production and editing support from Sarah Lamodi, edited by Ryan Mulcahy and Paul Makishima. Original music and sound designed by Noel Flatt, produced by Harvard University. Copyright 2025.