‘Harvard Insights’: Cancer is increasing among younger populations — what’s the reason?

Kimmie Ng: A person born in 1990 now has four times the chance of developing colorectal cancer and more than twice the chance of developing colon cancer compared to a similarly aged individual from 1950.

Samantha Laine Perfas: In contrast to overall cancer trends, certain cancer diagnoses in individuals under 50 have increased. From 2010 to 2019, the occurrence of 14 types of cancer rose among this age group. The crucial inquiry is, why? Is it linked to lifestyle decisions? Are there environmental influences involved? What measures can be taken to lower the risk?

Welcome to “Harvard Insights,” a podcast where intellectual discussions intersect with everyday realities. Today I’m joined by:

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

Laine Perfas: He specializes in cancer epidemiology and analyzes global cancer trends and disparities. Next:

Ng: Kimmie Ng. I am an associate teacher of medicine at Harvard Medical School.

Laine Perfas: Additionally, she is a medical oncologist at Dana-Farber Cancer Institute and the founding director of the Young-Onset Colorectal Cancer Center. And our concluding guest:

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

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

And I’m Samantha Laine Perfas, your host and a writer for The Harvard Gazette. Today we’ll delve into early-onset cancer and discuss how younger individuals can manage their heightened risk.

It is essential to begin with the broader context of cancer trends overall, which indicates rates have been declining in recent times. However, certain cancers are witnessing an upsurge, particularly among individuals

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under 50. What are we observing?

Ugai: I believe that when we discuss the rise in early-onset cancer, it’s not a straightforward narrative. The frequency of early-onset cancer has been escalating in various regions globally, but this varies among different cancer types, locations, and nations. Hence, we need to delve deeper into these disparities. Our latest analysis indicates that numerous early-onset cancer types, such as colorectal cancer, breast cancer, uterine cancer, kidney cancer, pancreatic cancer, and multiple myeloma, have escalated more swiftly than late-onset cancer types. Moreover, for both colorectal and uterine cancers, both incidence and mortality have risen simultaneously. This trend is primarily seen in high socioeconomic countries like the United States, the United Kingdom, Australia, and New Zealand.

“Our latest analysis indicates that numerous early-onset cancer types, such as colorectal cancer, breast cancer, uterine cancer, kidney cancer, pancreatic cancer, and multiple myeloma, have escalated more swiftly than late-onset cancer types.”

Rebbeck: To add to what Tomo mentioned, one of the particularly intriguing observations he made is that over the last couple of decades, we’ve witnessed an increase in cancers diagnosed in individuals under the age of 50, across various tumor locations globally, among both men and women. This occurrence is something we have scarcely observed in the past. The last instance where we saw such a global phenomenon with significant changes was lung cancer in the mid-20th century, which transitioned from being a rare cancer to the most prevalent one. We quickly figured that out; it was due to cigarette smoking. In this scenario, we’re likely discussing major exposures or similar factors, but we’re also recognizing many different cancers worldwide. Therefore, something fundamentally significant and fascinating is happening here.

Ng: What’s notable is that if you examine the epidemiological trends carefully, they reflect what we refer to as a birth cohort effect, where the rise varies significantly by generation. For instance, an individual born in 1990 now possesses a fourfold higher risk of developing colorectal cancer and more than double the risk of colon cancer in comparison to someone of the same age born in 1950. This is crucial as it provides insights into the potential underlying causes of these rising trends. Generally, a birth cohort effect suggests a combination of environmental exposures that are impacting incidence across generations.

Laine Perfas: Kimmie, could you elaborate on the birth cohort effect and also share your experiences regarding the treatment of patients who are now developing these cancers at a younger age?

Ng: If we analyze the trends, the increase has been evident across every birth cohort since 1950. However, these trends have been formally documented in the published literature since around the mid-1990s. For colorectal cancer, for example, we have observed about a two percent annual increase in colorectal cancer rates among both men and women since the mid-1990s, and it is estimated that by 2030, colorectal cancer will become the leading cause of cancer-related fatalities in individuals under 50.

It is widely recognized that the challenges confronted by younger individuals diagnosed with cancer significantly differ from those faced by older individuals. This necessity contributed to our establishment of a dedicated Young-Onset Colorectal Cancer Center, enabling us to better address these unique challenges affecting young people, which encompass issues regarding fertility—many of these individuals are still attempting to expand or initiate their families. It encompasses sexual health, career, and educational disruptions. Moreover, over 80 percent of young colorectal cancer patients have children under the age of 18 when they are often diagnosed with an advanced stage of disease. Many also belong to the sandwich generation, caring for aging parents. It is a particularly challenging time to receive a terminal cancer diagnosis. Consequently, there are elevated levels of psychosocial distress. Many require social work and psychiatric assistance, and we are striving to provide all of that through our center.

Laine Perfas: It’s intriguing that the last time a similar phenomenon occurred, it was with lung cancer, which was directly linked to cigarette smoking. Do we have any insights into what might be influencing the current trends?

Rebbeck: We certainly have numerous hypotheses that seem plausible. Many of these include diet, lifestyle, obesity, alcohol consumption, and tobacco use. They represent significant exposures that must be fairly widespread to explain the rate changes we’re witnessing. They would need to be general carcinogenic exposures, impacting cancers at various sites. Because that’s what we’re observing. They need to affect both men and women, as evidenced by the epidemiological data. Furthermore, they likely represent changes experienced globally over the past few decades. One can speculate what some of these factors might be. I anticipate we’ll hear more from Tomo and Kimmie regarding this and some of their research. However, obesity aligns with this pattern very well. Obesity has surged significantly in recent decades and has transformed across the globe. It’s prevalent among both genders, particularly among children. If obesity is a primary explanation for these trends, it’s likely emerging earlier in life among children. The lag we’re observing between changes in exposure and the emergence of early-onset cancers probably began earlier in life, correlating with early-onset cancers. All of these factors seem to align, but I suspect they aren’t the only explanations. There are numerous other hypotheses, such as microplastics, and other alterations that have taken place in recent decades to consider.

Ugai: I believe there are several significant indicators for potential causes behind the rise in early-onset cancers. First, as Kimmie pointed out, there exists a birth cohort effect, indicating that more recent generations face a greater risk of early-onset cancers; this effect is associated with changes in environmental or lifestyle factors over several years. For instance, numerous lifestyle factors like obesity, lack of physical activity, dietary habits, and various environmental factors such as air pollution have undergone significant changes since 1940 to 1950, which may be a critical factor.

“There are several significant indicators for potential causes behind the rise in early-onset cancers. … Numerous lifestyle factors like obesity, lack of physical activity, dietary habits, and different environmental factors such as air pollution have undergone significant changes since 1940 to 1950.”

Second, as I noted earlier, several early-onset cancer types have escalated more quickly than late-onset cancers. This implies that particular exposures, such as new or established risk factors, have shifted towards younger populations. For instance, the incidence of obesity has risen among younger demographics, but factors like pollution or microenvironments, along with other toxins, might be regarded as potential novel risk factors for early-onset cancers.

Ng: To continue our discussion regarding obesity, I concur it has been proposed as the primary hypothesis…

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for the reasons early-onset cancers have been increasing worldwide. And indeed, if you examine the cancer categories that have been escalating in younger individuals, they are all linked to obesity, including endometrial cancer and cancers of the gastrointestinal tract, which not only comprise colorectal cancer but also pancreatic cancer, cancers of the biliary system, appendix cancers, and many more. Nevertheless, I can assure you that in our facilities here at Dana-Farber, most of the patients we encounter are not overweight and lead vigorous and healthy lifestyles. They consume nutritious foods. Therefore, while obesity is undoubtedly a factor in these rising statistics, it is likely not the sole explanation.

“In our facilities here at Dana-Farber, most of the patients we encounter are not overweight and lead vigorous and healthy lifestyles. … Therefore, while obesity is undoubtedly a factor in these rising statistics, it is likely not the sole explanation.”

Laine Perfas: There are indeed young and active individuals in my life who are stunned to discover they have cancer, and not all of these cases are easily treatable; some are quite aggressive. Considering the trends, it’s difficult not to think, I was born in the ’90s; is this a reality my generation faces, with my rates potentially being four times greater than those born in the 1950s, irrespective of my choices? Do we possess more control than that?

Ng: I would emphasize that adhering to a nutritious diet and lifestyle while maintaining a healthy body weight remains critically significant. I believe Tim pointed out that the behaviors and factors in early life represent an essential window of exposure that increases the risk of these cancers in young adulthood.

Thus, I still consider it crucial for public health organizations and the healthcare system overall to instruct children and adolescents about the importance of a nutritious diet and active lifestyle, as well as maintaining a healthy body weight. Such measures are likely to not only shield you against the development of various cancers at any age but also against numerous other chronic health issues.

Rebbeck: Another aspect I would like to add is that, depending on how this message is received by someone born in the ’80s or ’90s, it could lead to panic. It’s vital to keep in mind that most of these cancers continue to be predominantly identified in older individuals over 50. It’s not the case that those under 50, or even 40, are now primarily diagnosed with these cancers. It is certainly true that there is a significantly higher risk of cancer now than there was previously if you’re under 50, but it still remains relatively uncommon.

Ugai: I want to follow up on Kimmie’s very crucial point regarding early-life exposures. Research shows that a healthy diet in early life correlates with a reduced risk of early-onset colorectal cancer. Hence, if you’re a parent, you can start fostering healthy diets or lifestyles as soon as possible. Simultaneously, educating children about these healthy practices can help minimize their risks.

Laine Perfas: We can certainly embrace healthier habits, but I also want to discuss genetics, something beyond our control. What impact do genetics have?

Rebbeck: It is widely recognized that individuals with a hereditary predisposition to cancer often receive a diagnosis at a younger age. For instance, those diagnosed with hereditary breast cancer due to a BRCA1 or BRCA2 mutation typically receive their breast cancer diagnosis on average 10 years younger than the general population. Genetics, especially these high-penetrance hereditary cancer patterns, are indeed linked with earlier onset ages. However, what we do not observe or anticipate is that alterations in the germline genetic patterns that create these exceptionally high risks have changed significantly over the past several decades. We do not expect that germline genetics, including frequencies or types of mutations, have shifted so considerably to account for the majority of differences in early-onset diagnoses we have noted. Even so, cancer is fundamentally a genetic condition. There is always an underlying predisposition to cancer present. It is possible and perhaps even probable that gene-environment interactions are occurring, where individuals with an underlying susceptibility are now being exposed to significant risk factors, resulting in earlier diagnoses due to those gene-environment interactions.

Ng: This topic is incredibly significant because I entirely concur; when examining gastrointestinal cancers occurring in individuals under 50, around a quarter can be attributed to a hereditary cause for developing cancer at a young age. However, that leaves 75 percent with sporadic cancers unrelated to family history or hereditary predisposition. Given that you are more likely to identify a hereditary condition the younger you are diagnosed, it is essential that the standard care protocols include hereditary genetic testing for any young individual diagnosed with cancer under the age of 50.

Laine Perfas: I’m eager to hear your thoughts regarding the reduction of screening ages for various cancers. For example, colorectal cancer screening ages have been decreased from 50 to 45. Breast cancer screening has actually varied multiple times. What are the advantages and disadvantages of early screening?

Ugai: As you mentioned, in 2018, the American Cancer Society recommended starting colorectal cancer screening at age 45 rather than age 50 for average-risk populations. Personally, I believe this strategy would be effective. However, at the same time, we need to consider factors such as cost-effectiveness, invasiveness, and potential complications. This is somewhat challenging to determine.

Rebbeck: To Tomo’s point, since cancers are indeed rarer at younger ages, lowering the screening age is inherently less efficient. We will uncover fewer cancers if we screen the same number of individuals because they are simply less prevalent. Thus, the notion of adjusting cancer screening ages for those we can examine, such as in colorectal and breast cancer, likely yields reduced benefits. We need to assess the risks, trade-offs, and cost-benefit analysis, which are crucial considerations for public health.

Ng: I truly believe that reducing the screening age for average-risk individuals for colorectal cancer to 45 is a positive first step in the correct direction. The majority of young-onset colorectal cancers are diagnosed in individuals in their 40s. However, returning to those epidemiological trends, the rates of increase are actually steepest in the very youngest patients who are below the eligible screening age. Therefore, it’s clear that merely lowering the age or basing screening recommendations solely on chronological age is insufficient to tackle the issue of early-onset cancers. I think this underscores the necessity for…

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significance of conducting the study to enhance comprehension, what precisely are the risk determinants? Who faces the risk? What are the origins? Furthermore, can we pinpoint the youth who are more susceptible to colorectal cancer and focus on them for preliminary screening?

Rebbeck: I believe that’s critically significant, as we’ve observed that community-oriented screening possesses value in numerous contexts, yet risk-adaptive screening methodologies are emerging as increasingly pertinent and suitable, particularly in this instance. For instance, not only in breast cancer do we contemplate different methods of screening, such as employing MRI for very young women instead of mammography, but also the timing and frequency of those screenings. Thus, as we begin discussing more atypical individuals due to their risk, and in a rarer scenario such as colorectal cancer in the 30s, broad-based screening becomes less compelling, and a focused screening strategy or timely detection approach is likely what we should be increasingly considering.

Laine Perfas: Have modifications in screening made an impact or is it still premature to determine?

Ng: A recent article published in JAMA this month indicated that the adoption of colorectal cancer screening among individuals aged 45 to 49 has been gradually increasing since the United States Preventive Services Task Force revised their guidelines to lower the age. In fact, there seems to be a hopeful shift towards identifying more early-stage cancers now due to these recent guideline adjustments. Thus, I believe it is beginning to take effect. It is still in the early stages, but I do hope the adoption will persist.

Rebbeck: One of the intriguing observations is that most of the cancers we’re discussing lack screening methods. Colorectal cancer is undoubtedly the dominant player in this dialogue, partly due to its prevalence, but it also offers very clear, actionable interventions, like colonoscopy. The majority of other cancers do not have such options. I think while screening is vitally important, we can’t apply that framework to pancreatic cancer or kidney cancer or similar cases. Thus, there are numerous other factors we must consider beyond screening for the majority of these cancers.

Ugai: Additionally, I want to emphasize another crucial aspect regarding early-onset cancer and screening. The rise in early-onset cancer can perhaps be partially linked to improved screening and early detection. Furthermore, advancements in cancer registry systems or screening technologies can also influence the increased prevalence of early-onset cancers. Again, it is essential to gain a deeper understanding of the situation on a global level.

Laine Perfas: Are you suggesting that the rise in rates might be partially due to simply enhanced screening, meaning that these cancers may have existed before, but we were unaware of them due to a lack of screening?

Ugai: Yes, that’s accurate; for instance, in the cases of thyroid and prostate cancers, the data shows that the occurrence of early-onset prostate and thyroid cancers has been climbing over the last few decades. However, when analyzing both incidence and mortality, mortality has not increased. Hence, this rising trend might not be genuinely reflective but rather attributable to enhanced screening.

Ng: I want to highlight that this is not the case for colorectal cancer, correct? The increase has been observed since the mid-1990s when the recommended screening age was 50, and a significant number of young-onset colorectal cancer cases are diagnosed at advanced stages, Stage 3 or 4, which removes the possibility of this increase being a factor of screening.

Rebbeck: Absolutely. There’s a notable instance from South Korea a couple of decades ago where they initiated thyroid cancer screening, resulting in a dramatic rise in incidence. Mortality rates, however, remained unchanged, as there is a considerable amount of indolent thyroid cancer within the population that does not cause any issues. Similarly, as Tomo mentioned regarding prostate cancer, there is a vast amount of indolent prostate cancer. I am uncertain whether the same applies to colorectal cancer, as it is unlikely there is a substantial amount of indolent colorectal cancer that remains stagnant for many years without progressing. Therefore, I think each cancer type will differ. Each one likely requires distinct considerations regarding screening, overdiagnosis, and the worth of screening. They will all vary considerably.

As a note concerning prostate cancer, which I believe serves as an excellent early indicator for the scenarios we expect to encounter in cancer screening. The U.S. Preventive Services Task Force revised its guidelines on prostate cancer screening with PSA over several years. Most recently, in 2018, they recommended reducing the frequency of that screening, and in the following years, prostate cancer mortality rates have begun to rise. This change required time to manifest, and although it’s not classified as an early-onset cancer, I think that when we observe significant policy and guideline changes, if screening is impactful, we will eventually witness changes in mortality rates.

Ng: Indeed, it is vital to consider the unique screening practices of each nation while comparing global trends in early-onset cancer rates. For example, in Japan and South Korea, there exists population-based and opportunistic screening for gastric cancer. Consequently, the rates of gastric cancer have not been increasing among young or older populations in those regions. It is crucial to factor in the diverse practices of various countries when analyzing incidence trends.

Laine Perfas: It is well-acknowledged that early diagnosis is essential for effective and improved treatment. Beyond mere screening, what obstacles prevent earlier detection?

Rebbeck: Regarding colorectal cancer, it predominantly involves the capability and readiness of individuals to undergo colonoscopy. Kimmie could certainly elaborate on this from her experiences, but although colonoscopies are highly effective, they are unpleasant and challenging to complete. It’s not an easy procedure. There are identifiable barriers here, and I would be keen to hear others’ perspectives on a tiered methodology utilizing fecal occult blood or FIT testing as a complement to colonoscopy. Are there more effective approaches that might enhance the capacity to identify cancers even among individuals who may be hesitant to undergo the gold-standard colonoscopy?

Ng: Besides personal reasons that might deter someone from getting a colonoscopy, there are also myriad logistical hindrances, right? Particularly for those juggling multiple jobs who cannot afford time off to prepare for the procedure and need to arrange transportation to and from their colonoscopy. These represent genuine challenges faced by many daily, significantly hindering their ability to undergo screening. Therefore, this is why it is crucial that the United States Preventive Services Task Force offers various testing alternatives for colorectal cancer screening. A home-based stool test may be significantly simpler for individuals than navigating all the logistics surrounding a colonoscopy appointment.

Ugai: In addition, I want to underscore the significance of raising awareness about early-onset cancers. Perhaps we should advocate more, but we can also partner with industries or policymakers to elevate awareness regarding early-onset cancers.

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Rebbeck: Additionally, I would include healthcare providers, primary care professionals, individuals who may be the frontline in recognizing those who exhibit signs of colorectal cancer, particularly when the patient is 30 years old and may overlook it or attribute it to another issue. Therefore, I believe there is a significant need for awareness at various levels to guarantee that individuals enter the appropriate care pathways as early as possible.

Ng: I also believe there exists a stigma associated with certain cancers that hinders discussions about diagnoses and symptoms. Patients often feel uncomfortable mentioning bowel-related symptoms to their primary care providers or even broaching the subject with family members. Therefore, I think fostering open discussions regarding these topics will greatly contribute to increased awareness.

Laine Perfas: There remains an enormous amount we are yet to uncover. What areas should we be exploring or focusing our research on for future insights?

Rebbeck: The broad response would be to comprehend the lifestyle factors, obesity, body fat, and environmental influences likely involved. We already possess many indications from existing studies, but executing these studies can be incredibly challenging, requiring substantial sample sizes conducted meticulously. They may necessitate long-term cohorts that could span years or decades. The gold standard for identifying such risk factors will not yield immediate results.

Ng: This represents an exceptionally complex issue to investigate, and life course studies are perhaps the most effective means of comprehending what occurs in childhood that subsequently increases cancer risk during young adulthood. However, those studies are time-consuming and often prohibitively costly. Honestly, we cannot afford to wait that long for solutions. Given the intricate nature of this phenomenon, a collaborative approach is vital. We need epidemiologists, oncologists, basic scientists, and environmental health specialists to unite in efforts to grasp the underlying causes.

Rebbeck: There might be an excellent opportunity for a swift progression in basic science. Basic research can be accomplished much more promptly than extensive epidemiological studies. If we had a clearer understanding of the molecular origins and mechanisms behind early-onset cancers, we could explore whether these differ from late-onset cancers. Are the molecular characteristics of those tumors distinct?

Ng: For instance, a recent publication in Nature unveiled a mutational signature in DNA attributed to a genotoxin known as colibactin, which appears to be significantly more prevalent in younger individuals diagnosed with colorectal cancer compared to older patients. This is promising because it represents initial evidence that the microbiome, particularly a bacterium called pks+ E. coli, is responsible for producing colibactin that damages DNA. While it won’t clarify all cases of early-onset colorectal cancer, it potentially implicates the microbiome as a factor contributing to this global occurrence.

Laine Perfas: What recommendations do you have to empower our audience to take charge of their health and reduce their cancer risk?

Rebbeck: Awareness is crucial. Recognize the symptoms associated with these cancers and inquire questions. Seek knowledge not only about colorectal cancer but also regarding numerous early-onset cancers in individuals under 50. As Kimmie mentioned earlier, maintaining a healthy lifestyle is vital: Eat a balanced diet, engage in physical activity, and manage your weight – all critical pieces of advice we’ve received concerning cancer and other illnesses. These empowering actions can be undertaken by individuals; while they may not be easy, they are achievable in reducing risks.

Ng: I would also emphasize that for cancers with established screening guidelines and programs, it’s important to get screened, as this could save lives. Additionally, knowing your family history is essential, particularly if relatives have experienced that cancer at a young age; this may enable you to qualify for earlier screenings, which can also be life-saving.

Ugai: The key factors are a healthy lifestyle and a nutritious diet. Notably, many common cancer risk elements overlap between early-onset and standard-onset cancers. Therefore, by avoiding established cancer risk factors, one can also minimize the likelihood of other non-communicable diseases. Early life exposure can be quite significant, so it’s beneficial to mitigate cancer risk factors as soon as possible. Simultaneously, promoting a healthy lifestyle to younger generations is crucial. I believe that’s paramount.

Laine Perfas: Thank you all for your time today and for sharing your insights with me.

Rebbeck: Thank you for having us.

Ng: Thank you for the invitation.

Laine Perfas: Thank you for tuning in. If you wish to view a transcript of this episode or check out our other episodes, visit harvard.edu/thinking. To support us, please 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 assistance from Sarah Lamodi, edited by Ryan Mulcahy and Paul Makishima. Original music and sound design by Noel Flatt, produced by Harvard University. Copyright 2025.