Although it’s been widely reported for years that colorectal cancer incidence has been increasing among younger adults under age 50 by between 1% and 2% annually since the mid-1990s,¹ two new studies by Kimmie Ng, MD, MPH, Associate Chief of the Division of Gastrointestinal Oncology and Founding Director of the Colon and Rectal Cancer Center at Dana-Farber Cancer Institute, and Associate Professor of Medicine at Harvard Medical School, and her colleagues, find other alarming trends in early-onset gastrointestinal cancers.

According to the studies’ results, the incidence of early-onset gastrointestinal cancers rose by 14.8% between 2010 and 2019, and is increasing faster than other types of early-onset cancers, such as breast cancer, and includes, in addition to colorectal cancer, rises in pancreatic, esophageal, stomach, appendix, biliary cancers, and neuroendocrine tumors.^2,3 In addition, the findings show that these early-onset gastrointestinal cancers disproportionately affect Black, Hispanic, and Indigenous individuals, and women.

“The rise of early-onset colorectal cancer has been in the news for so long, it was like a warning of things to come,” said Dr. Ng. “It was the first indication that something bigger was going on with all these other gastrointestinal cancers rising in these young people, which is very distressing.”

To improve survival outcomes and cancer prevention in early-onset cancers, we need to figure out what the etiology is that is driving these cancers, and we need to find good biomarkers that can be tested relatively easily and inexpensively on a population-wide basis for screening and early detection. In the meantime, raising public awareness about early-onset cancers is going to be important for early detection and improved survival outcomes.

— KIMMIE NG, MD, MPH

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Taken together, the review of the two studies shows potential explanations of the rise in early-onset gastrointestinal cancers. They include both modifiable lifestyle factors, such as obesity, poor diet, inactivity, smoking, and alcohol use; and nonmodifiable factors, such as chronic conditions, including inflammatory bowel disease, as well as family history and hereditary disorders like Lynch syndrome. According to Dr. Ng, between 15% and 30% of these cancers have pathogenic germline variants, indicating a hereditary predisposition to developing cancer. “However, the hereditary part is not enough to explain why these cancers are rising so rapidly in these young individuals,” said Dr. Ng.

Determining what lifestyle factors that might be involved in the development of these early-onset cancers is also proving to be elusive. “What we know is that something in our environment, whether that is diet or some other lifestyle factor or some other environmental toxin, is causing the rise we see in these early-onset cancers. But I can tell you that so many of our young patients are not obese, they are physically active, and they do follow healthy diets and lifestyles. So, what is actually leading to this increase is still being investigated.”

In this wide-ranging interview with Dr. Ng, she discussed why early-onset cancers are increasing in younger adults, the role of colibactin-producing bacteria in the development of these cancers, and their potential biological drivers.

Investigating the Role of the Microbiome in the Development of Early-Onset Colorectal Cancer

According to a report by the American Cancer Society, the incidence of colorectal cancer in young adults aged 20 to 39 has been rising at about 2% a year since the mid-1990s.¹ In addition, colorectal cancers have become the leading causes of cancer-related death in men and the second leading cause in women behind breast cancer in individuals under age 50.⁴Your reviews found that while early-onset gastrointestinal cancers are highest in people aged 40 to 49, younger individuals born in 1990 are twice as likely to develop colon cancer and four times as likely to develop rectal cancer compared with those born in 1950. What are you learning from your research about why colorectal cancer is increasing in these younger adults, especially in those without lifestyle or hereditary risk factors? What is it about the generational gap that is making colorectal cancer more prevalent in these young people?

You are right that the highest prevalence of these cancers is in individuals in their 40s. But the actual rate of rise is steepest in people in their 20s and 30s. So, the younger you are, the more rapidly these gastrointestinal cancers seem to be increasing in incidence.

In terms of what other environmental factors might be in play, one of the most impactful discoveries was published in a recent study showing that the presence of colibactin, a genotoxic bacterial toxin, primarily produced by polyketide synthase (PKS) E. coli strains, in the microbiome is three times more common in young patients under the age of 40 with colorectal cancer compared to older patients with colorectal cancer.⁵ This finding implicates the microbiome as a potential contributing factor as to why early-onset colorectal cancer might be increasing in younger adults.

What’s also interesting about this study is that the researchers found that this PKS-positive E. coli organism is likely present in the microbiome in the first decade of life, and causes the mutational signatures SBS88 and ID18, which are enriched in early-onset colorectal cancers. Polyketide synthase–positive E. coli can disappear from the microbiome, and is not found in most of the young patients diagnosed with colorectal cancer, which shows the layers of complexity in studying this cancer.

We are now trying to figure out what the factors are that lead to the presence of PKS-positive E. coli in some individuals in the first 10 years of life. There are some preliminary data showing that maybe the Western-pattern diet and a diet low in fiber are associated with finding this organism in the microbiome. So, perhaps this strengthens the theory that diet and lifestyle do influence the development of early-onset colorectal cancer. We just don’t have a definitive answer yet.

Understanding Why Early-Onset Pancreatic Cancer Is Rising in Women

It was especially troubling to see in your study results that worldwide, early-onset pancreatic cancer is the fourth most common cancer in younger adults, with 29,402 individuals diagnosed each year, globally, and nearly 3,000 diagnosed in the United States alone.² Other studies are showing similar trends in pancreatic cancer developing in younger adults, chiefly in younger women, particularly Black women.⁶ Are there some theories emerging regarding why this cancer is increasing in this population? For example, is tumor location in the pancreas a factor?

There aren’t any definite associations between the location of the pancreatic tumor and the development of early-onset pancreatic cancer. But research on this cancer is hard to conduct because early-onset pancreatic cancer is still relatively rare, and there are relatively few numbers of these patients to include in studies to draw definitive conclusions. Right now, we don’t have adequately powered studies for us to fully understand all of the different, unique characteristics of early-onset pancreatic cancer.

What our review paper showed is that early-onset pancreatic cancer does seem to be rising more rapidly in women. We see that same pattern in early-onset gastric cancer.

What is especially concerning is that the prognosis in pancreatic cancer is so terrible. It’s very, very hard to see someone in their 30s or 40s being diagnosed with metastatic pancreatic cancer. Unfortunately, we are seeing this diagnosis more commonly now in younger adults.

Studying the Biological Differences in Early- and Later-Onset Cancers

What is your research showing about the biological differences between early- and later-onset gastrointestinal cancers?

In the case of early-onset colorectal cancer, we are currently doing several multiomics analyses to try to understand the biology of those tumors on a cell-by-cell level and how they may differ from later-onset disease, and we are finding some interesting differences. We hope to publish some of the results soon.

What I can say is we do think the microbiome may be playing a role, particularly with the PKS-positive E. coli finding I talked about earlier in the development of early-onset colorectal cancer. That finding doesn’t account for all early-onset colorectal cancers, but it may account for a proportion of them.

Guest Editor

Brandon Hayes-Lattin, MD, FACP

Brandon Hayes-Lattin, MD, FACP, is Professor of Medicine, Deputy Division Head of Hematology and Medical Oncology, and Director of the Adolescent and Young Adult Oncology Program at the Knight Cancer Institute at Oregon Health and Science University, Portland.

The reason we think there may be biological differences between early-onset and later-onset cancers is that the survival rate in younger patients is not necessarily better than it is in older patients, although the data are conflicting. Some data show a survival benefit for younger patients, but in general, especially for early-onset colorectal cancer, despite usually more aggressive therapies, these patients don’t always live longer, particularly the very youngest patients under the age of 35.

Raising Public Awareness About Early-Onset Cancers to Improve Survival Outcomes

Colorectal cancer screening guidelines call for individuals at average risk of the cancer to be screened starting at age 45,⁷ but there are no official guidelines for screening tests for other gastrointestinal cancers. Will the development of multicancer early detection tests provide screening options for young adults concerned about their cancer risk?

Potentially, yes. I do think there may be a role for these noninvasive blood tests in the future, but they are not yet ready for prime time. And they should not be used to replace screening tests for cancers that already have established guidelines.

To improve survival outcomes and cancer prevention in early-onset cancers, we need to figure out what the etiology is that is driving these cancers, and we need to find good biomarkers that can be tested relatively easily and inexpensively on a population-wide basis for screening and early detection. In the meantime, raising public awareness about early-onset cancers is going to be important for early detection and improved survival outcomes.

DISCLOSURES: Dr. Ng reports receiving research funding to her institution from Pharmavite LLC and Janssen. She is also on the advisory board of CytomX, Revolution Medicines, Agenus, Johnson & Johnson, Manta Cares, AbbVie, AstraZeneca, and Amgen; and is the Associate Editor at JAMA.

REFERENCES

1. Siegel RL, Wagle NS, Cercek A, et al: Colorectal cancer statistics, 2023. CA Cancer J Clin 73(3):233-254, doi.org/10.3322/caac.21772, 2023.
2. Jayakrishnan T, Ng K: Early-onset gastrointestinal cancers: a review. JAMA doi: 10.1001/jama.2025.10218, 2025.
3. Char SK, O’Connor CA, Ng K: Early-onset gastrointestinal cancers: comprehensive review and future directions. BJS 112(7), znaf102, doi.org/10.1093/bjs/znaf102, 2025.
4. Collins S: 2024—First Year the US Expects More Than 2M New Cases of Cancer. American Cancer Society January 17, 2024. Available at www.cancer.org/research/acs-research-news/facts-and-figures-2024.html.
5. Díaz-Gay M, dos Santos W, Moody S, et al: Geographic and age variations in mutational processes in colorectal cancer. Nature 643(8070):230-240, doi: 10.1038/s41586-025-09025-8, 2025.
6. Abboud Y, Samaan JS, Oh J, et al: Increasing pancreatic cancer incidence in young women in the United States: a population-based time-trend analysis, 2001-2018. Gastroenterology 164(6):978-989.e6, doi: 10.1053/j.gastro.2023.01.022, 2023.
7. U.S. Preventive Services Task Force: Final Recommendation Statement: Colorectal Cancer: Screening. May 18, 2021. Available at www.uspreventiveservicestaskforce.org/uspstf/recommendation/colorectal-cancer-screening.