The Rise of Early-onset Cancers: Leading Hypotheses and Emerging Opportunities 

Research-driven advances in cancer prevention, early detection, and treatment have led to an impressive 33% reduction in the cancer mortality rate over the past three decades. At the same time, however, there has been an alarming increase in the number of younger individuals developing—and dying from—cancer. 

“What is especially concerning is that these young adults are presenting with metastatic disease or advanced local disease that often is deadly,” said Elizabeth M. Jaffee, MD, FAACR, AACR Past President, deputy director of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University School of Medicine, and one of the cochairs of the upcoming AACR Special Conference: The Rise of Early-onset Cancers—Knowledge Gaps and Research Opportunities, which will be held December 10-13 in Montreal. 

While some of the increased diagnoses in younger individuals might be attributable to advances in screening, fellow conference cochair Timothy R. Rebbeck, PhD, FAACR, noted that most patients diagnosed with early-onset cancers (defined as those diagnosed before age 50) are too young to be eligible for routine screenings, and many are diagnosed with cancers for which there are no available screening tools.  

“We do not yet understand why these cancers are becoming more common, but it doesn’t appear to be solely a consequence of enhanced screening,” said Rebbeck, who is a professor of cancer prevention at Harvard University and a professor of medical oncology at Dana-Farber Cancer Institute. He added that early-onset diagnoses have been rising across cancer types, in multiple countries, and in both men and women.  

“The rising incidence appears to be a birth cohort effect, where we are seeing increased cancer diagnoses in those born in 1950 or later,” said Andrea Cercek, MD, section head of colorectal cancer and a codirector of the Center for Young Onset Colorectal and Gastrointestinal Cancer at Memorial Sloan Kettering Cancer Center and the third cochair of the conference. “That really suggests that the rise is a result of something environmental. What that is, no one knows, but that is why we are having this conference.” 

Jaffee, Rebbeck, and Cercek spoke with Cancer Research Catalyst about the possible factors underlying the rising rates of early-onset cancer, some of the field’s top priorities, and how the conference aims to raise awareness and drive progress. 

What are the leading hypotheses for why early-onset cancers are rising in incidence? 

Jaffee: One thought is that the rising incidence could be due to the increasing rate of obesity and changes to diet, lifestyle, and environmental exposures that have occurred since the 1990s. 

The strongest evidence supports a role for obesity and lifestyle changes. People are more sedentary, exercising less. There’s a lot of work that has shown that changes in both weight and physical activity increase your risk for cancer.  

It is also possible that environmental changes and increased antibiotic use are changing our microbiomes. These changes might be detrimental if they result in fewer good bacteria that typically help prevent inflammation, which we know can lead to cancer.  

We have seen the rise in early-onset cancers in multiple regions of the world, but the exposures that lead to their development may vary across different countries. In some countries, diet and obesity may play a bigger role, while in others—particularly low- and middle-income countries—increasing rates of infectious disease may be the primary factor. Whatever the cause—viral infection, obesity, exposure to toxins—in the end these probably all converge on the same cancer-causing biological mechanisms, namely chronic inflammation. 

Rebbeck: The rates of obesity in childhood and younger individuals have been increasing over many decades, which parallels the rise in obesity-related cancers. Certainly, a lot of research has gone into examining how obesity might contribute to the rise of early-onset cancers. 

But there are several other possible underlying causes. Some of those could be exposures we don’t understand well, such as exposure to microplastics or pollution at a very early age—even in utero. Unfortunately, studies to understand the impact of environmental exposures are difficult to conduct. We don’t have adequate methods to assess exposures at very early ages and then continue to track them for 30 to 40 years until cancer develops.  

For this reason, the conference will not only examine the potential mechanisms by which environmental exposures might promote early-onset cancer, but it will also explore methodologies so that we can better study these factors. 

What are some important areas of research for the field? 

Rebbeck: One is to better quantify incidence of early-onset cancers around the world so we can understand who is at risk, which cancers are rising, and where they are being diagnosed most frequently. 

Second is to consider how cohorts can be leveraged for use in assessing risk factors, or develop new cohorts if existing cohorts don’t have data from the right time frame or have not measured the variables we are interested in. This is a long-term endeavor because establishing new cohorts and following them through to cancer onset will take decades. 

The third priority is to study the biological mechanisms underlying early-onset cancer development. We need to understand how quickly cancers might start developing after an exposure to a carcinogen and study whether cancer initiation mechanisms are the same or different between early-onset and late-onset cancers. Is it that the mechanisms are the same but just starting earlier, are early-onset cancers just growing more rapidly than late-onset ones, or are there different mechanisms driving early-onset cancers?  

Cercek: One focus is to understand the population that is at risk of early-onset cancers. If we accept that environmental exposures are contributing to the risk, then why aren’t we all developing these cancers? Once we can identify who is most likely to develop early-onset cancers, then we can target screening efforts more effectively. 

That leads into another research focus, which is to develop improved screening technologies, especially for cancer types for which there are currently no screening tools available. Finally, understanding how to prevent or intercept early-onset cancers is the ultimate goal.

How will these research priorities be examined during the conference? 

Jaffee: We wanted to examine the topic of early-onset cancer from multiple angles, and I’m very excited about the broad approach we’ve taken in designing the program for this conference. To begin, we will have a session on epidemiology, chaired by Dr. Rebbeck, that is going to show us correlations between incidence and changes in diet, environmental patterns, and exposures. This is an important starting point that gives us clues into possible underlying causes and who might be at risk.  

We will also have a session exploring how social determinants of health impact lifestyles, and how these impacts on lifestyle can lead to differences in diet, obesity rates, environment-mediated metabolic alterations, and exposures to carcinogens. We will discuss how these could contribute to disparities in early-onset cancer incidence not only in the United States, but also very importantly, globally.  

In another session, chaired by Dr. Cercek, we hope to learn how to mitigate risk by taking a look at other diseases where there’s been successful control of risk factors, such as cardiac disease and diabetes. Presenters will discuss how these diseases were studied and how they successfully encouraged changes in lifestyle and diet to mitigate risk.  

In addition, the conference will include presentations on the role of the immune system, including chronic inflammation—which can be caused by infection or obesity, among other causes—in the risk for various diseases. Understanding how normal immunity leads to abnormal immunity and subsequent disease will provide clues into how we can intercept cancers, a topic that will be discussed in a session I am chairing. 

There will also be discussions surrounding cancer screenings, so we are really taking a holistic approach to examine all the major research directions for the field—from looking at epidemiologic studies all the way to prevention, early detection, and potential interceptions to stop these cancers in their tracks. 

Tell us about the sessions that will examine the epidemiology of early-onset cancers.  

Rebbeck: I’ll be chairing the first session, which will examine incidence and mortality trends of early-onset cancers, as well as how these correlate with environmental exposures.  

A separate session, chaired by Tomi Akinyemiju, PhD, will examine potential global disparities in early-onset cancer incidence. We have seen early-onset cancers rising around the world, but it is still not clear whether there are certain regions where it is more common.  

During the meeting, we are going to hear from epidemiologists and other experts about how to better collect data and quantify the changing rates of early-onset cancers. We need to understand if there are populations or countries where early-onset cancers are not rising so that we can compare the lifestyle and environmental factors between these groups and those in which early-onset cancers are rising to identify potential risk factors. 

Tell us about the session you will be chairing on learning from other diseases. 

Cercek: I’m very excited about this session, “Leading Hypotheses—Learning from Commonalities Across Diseases.” I proposed this topic to help us as cancer researchers break out of our silos in order to identify new research directions and strategies for managing risk.  

When we take a step back and examine health trends more broadly, what we realize is that there are similar trends across medicine. In addition to rising rates of early-onset cancer, we are also seeing earlier onset of menarche and a rising occurrence of early-onset atherosclerotic disease, to name a couple examples. Of course, it’s possible these trends are all occurring independently of one another, but what if they’re not? Could they be interrelated? 

Could there be a unifying factor or exposure that underlies all of these earlier onsets? If so, how would this play into how we attempt to mitigate risk for cancer? What can we learn from risk management from other diseases? Our hope is that this session will be hypothesis-generating and potentially lead to research collaborations.  

Tell us about the session you are chairing on interception strategies for early-onset cancers. 

Jaffee: The field is working to identify the earliest changes that launch the cascade of events to an invasive cancer to shed light on potential interception strategies for cancer in general. This session aims to discuss the interception opportunities that currently exist and how they can be improved upon or adapted for early-onset cancers, as well as potential new strategies. 

One strategy under exploration is vaccination to target the earliest changes, such as oncogene activation, that occur when a normal cell transitions to a cancer cell. This strategy is showing promise for pancreatic cancer, and we are currently testing a KRAS-targeted vaccine in patients who are at risk for pancreatic cancer. 

Another interception or primary prevention approach could be to target obesity. If obesity is a major cause of early-onset cancer development, maybe we could intercept with some of these GLP-1 inhibitors. This would also lead to reduced obesity over time and hopefully a reduced incidence in cancer. A recent retrospective analysis found that GLP-1 inhibitor use was associated with lower cancer incidence, which suggests that this might be a viable approach for curbing early-onset cancer rates. 

How might the rise in early-onset cancers impact screening guidelines? In your opinion, should cancer screenings begin at an earlier age?  

Rebbeck: It’s a complex question. The problem with beginning screening at an earlier age is that existing screening tools were initially developed for older individuals, so they may not be as sensitive to detect cancer in younger people. We know that mammograms, for example, are not as effective in younger women because of their typically high breast density. So, we need to develop new screening tools or optimize existing tools better suited for younger individuals.  

We may also want to think less about widespread population screening and more about targeted screening. For example, we might want to perform breast MRI in women who have a family history of breast cancer or a BRCA mutation.  

Cercek: As a colorectal cancer oncologist, I am seeing so many people in their 20s, 30s, and 40s getting diagnosed with colorectal cancer. Although early-onset cancers are still rare, by the end of this decade, we expect that about a quarter of all colorectal cancers will be diagnosed in adults under the age of 50—it’s unbelievable for a cancer that used to be considered a disease of people over the age of 60 and is also potentially preventable through polyp removal. 

So, from that perspective, yes, I think we need to start screening earlier. But it is simply not possible to perform colonoscopies in everyone starting at the age of 20, even in a resourced country like the United States. The recent guideline change that lowered the screening age to 45 is already putting a strain on the system. 

I think that the key will be better screening and early detection tools. While blood-based and stool-based screening are not as sensitive as colonoscopy, they’re a start. At the very least, maybe we can use these noninvasive tests in younger individuals to narrow down who might need a colonoscopy. 

What do you hope attendees take away from the conference? 

Jaffee: I hope attendees will get valuable insights into the leading hypotheses for why early-onset cancers are rising and will be inspired to pursue research in these areas. I would also like those who treat patients to learn about the risk factors for early-onset cancer so we can better identify patients who might be at increased risk. 

I also hope that we can engage more people to come into the field. By bringing the community together, we hope there might be an infusion of funding to help stimulate more research on this important problem.  

I’m so happy that the AACR is supporting this effort. Let’s face it, nobody wants to see anyone with cancer, but to see young people developing cancer and developing it at an advanced stage—I think we’re obligated to address it.  

Rebbeck: By hearing from researchers across different disciplines, I hope we will build momentum to accelerate research in this area. Because once we determine the major risk factors for early-onset cancer, we, as a society, can make policy decisions and other changes that will save lives. It is extremely timely to hold this type of conference now, while the research is building momentum in a coordinated way, rather than waiting until the science trickles in. 

Cercek: Whatever an attendee’s scientific niche might be, I hope they expose themselves to new ideas that will hopefully lead to fruitful collaborative efforts. The only way we will get close to solving the issue is to expand beyond our niches, collaborate, and continue to expand research efforts. 

Registration for the AACR Special Conference in Cancer Research: The Rise of Early-onset Cancers—Knowledge Gaps and Research Opportunities is now open. The advance registration deadline is October 31, 2025, and abstracts may be submitted until 1 p.m. ET on September 25, 2025.