Boston researchers find biological clues to why colon cancer hits younger patients harder

John Veale was 31, juggling work and graduate school in Boston, when he first noticed blood in his stool around Christmas 2024. He assumed hemorrhoids. Six months later, after finally getting a colonoscopy, he was diagnosed with Stage 4 colon cancer.

Veale's experience — a young person, a delayed diagnosis, an advanced disease — has become disturbingly common. Colorectal cancer is now the leading cause of cancer death among Americans under 50, and rates in that age group rose nearly 3 percent every year from 2013 through 2022, according to the American Cancer Society. The proportion of colorectal cancers diagnosed in people younger than 55 has doubled, from 11 percent in 1995 to 22 percent in 2022.

Now, a team of researchers from Dana-Farber Cancer Institute, Mass General Brigham, and the Broad Institute has published what they describe as the largest study of its kind — an analysis of 189 tumors and more than 850,000 individual cells — that offers the first detailed biological picture of how the disease differs in younger patients. The study appeared Thursday in the peer-reviewed journal Nature Medicine.

It's been a bit of a black box. Now we have a research direction. We have a path to follow and hopefully find something that's really specific to this disease and that will be the basis for developing tailored therapies specifically for young-onset colon cancer.— Ana Anderson, senior author and core faculty member, Gene Lay Institute of Immunology and Inflammation at Brigham and Women's Hospital

The researchers examined tumors from patients ranging in age from their 20s to their 90s, including 54 patients diagnosed before age 50. The most striking finding: tumors in younger patients contained a significantly higher proportion of stromal cells — connective and supporting tissue — relative to cancer cells. In studies of other solid cancers, a high stromal cell presence has been linked to resistance to chemotherapy. The team also identified differences in how genes are expressed in younger patients' tumors, which experts say could eventually point toward new therapeutic targets.

It gives a huge amount of hope. It really serves as a guidepost to where we should direct our future research efforts.— Dr. Kimmie Ng, senior author and director, Young-Onset Colorectal Cancer Center at Dana-Farber Cancer Institute

Outside researchers welcomed the dataset while noting its limits. Dr. John Paul Shen, an associate professor of gastrointestinal medical oncology at the University of Texas MD Anderson Cancer Center who was not involved in the study, said the findings point directly toward concrete follow-up experiments.

There's some very clear experiments that we might do in our lab or other people would do in their labs around the world. That's hugely valuable.— Dr. John Paul Shen, associate professor, gastrointestinal medical oncology, University of Texas MD Anderson Cancer Center

Shen and others cautioned that the cellular analysis, however detailed, is drawn from a relatively small number of patients. Ng said the cohort aligns with what is broadly known about young-onset colorectal cancer patients worldwide, and that future studies could expand to other patient groups.

The new tumor biology study lands against a backdrop of intensifying research into why younger generations are getting sick at all. The rise follows what epidemiologists call a birth cohort effect: every generation born after roughly the 1960s carries a higher risk than the one before it. According to Ng, a person born in 1990 has quadruple the risk of developing rectal cancer and more than double the risk of developing colon cancer compared with a similarly aged person born in 1950.

It's an absolute mystery and one of the big unanswered questions in medicine right now. Why are so many getting colorectal cancer at a younger age?— Dr. Kimmie Ng, founding director, Young-Onset Colorectal Cancer Center, Dana-Farber Cancer Institute

Because the rise has occurred over just a few decades — far too quickly to be explained by changes to the human genome — researchers have focused on environmental factors. Diet and obesity are among the leading suspects. Among adults ages 20 to 39, the prevalence of obesity more than doubled over 25 years, from about 18 percent in 1988–1994 to 40 percent in 2017–2018, according to CDC data cited by the AAMC. A 2026 analysis from the long-running Nurses' Health Study II found that women with the highest consumption of ultra-processed foods had a 45 percent higher risk of developing adenomas — precursor polyps associated with colorectal cancer. Sedentary behavior, sugar-sweetened beverages, and vitamin D deficiency have also been linked to risk.

One of the more unexpected leads involves bacteria. A study published in the journal Nature analyzed blood and tumor tissue from nearly 1,000 colorectal cancer patients across 11 countries, using DNA sequencing to identify mutational signatures — the genetic 'footprints' left by carcinogens. Researchers found a signature associated with colibactin, a genotoxin produced by certain strains of E. coli and other bacteria, at three to four times the rate in early-onset cases, particularly in patients under 40, compared with older patients.

We tried to understand when the mutation happened and our estimates are in the first ten years of life. The biggest window is somewhere between 9 and 18 months.— Ludmil Alexandrov, PhD, professor of cellular and molecular medicine, University of California San Diego, and lead author of the colibactin study

Colibactin-producing bacteria are estimated to be present in 40 to 50 percent of children in the United States and Western Europe, compared with about 5 percent in some developing regions, according to Alexandrov. He stressed that carrying the bacteria does not guarantee cancer — but it creates the conditions for DNA damage that could, over decades, contribute to it. Dana-Farber research has also found an association between being breastfed and a higher risk of colorectal cancer, for reasons that remain unclear, adding to the evidence that early-life exposures may be a critical window.

The research is necessary for us to understand why people are getting cancers early and what we can do about it.— Dr. Christina Annunziata, senior vice president of extramural discovery science, American Cancer Society

Annunziata called the new tumor dataset 'an essential first step' — a phrase that captures both the promise and the distance still to travel. Experts across the field agree that treatments tailored specifically to young-onset colorectal cancer remain years away, but that without studies like this one, the path there would have no map.

Why it matters — Colorectal cancer is now the top cancer killer of Americans under 50, and this study — the largest of its kind — gives researchers their first detailed cellular map of why the disease behaves differently in young people, opening a path toward treatments designed specifically for them.

Reported by bostonglobe.com, dana-farber.org, aamc.org