Why Are Colorectal Cancers Different in Young People? New Cell Atlas Published in Nature Medicine

Colorectal Cancer at a Young Age: The First Large Cell Atlas That Looks Inside the Tumor

Colon and rectal (colorectal) cancer is rising in people under 50 in many countries, and the reason is still not fully understood. A study published in Nature Medicine on October 29, 2026, approached the question from the side of tumor biology. Researchers examined more than 850,000 cell nuclei, one by one, in 189 tumors from patients aged 29 to over 90, and produced a map of how tumors change with age. In the most common subtype, younger patients' tumors had more support (stromal) cells, higher long non-coding RNA activity and patterns of cell-to-cell communication linked to the spread of cancer cells into surrounding tissue. These findings do not explain the rise, nor do they prove that the differences make the disease more aggressive; but they offer a new roadmap for research. We covered the broader picture in our articles on the rise in cancer under 50, colorectal cancer in children and adolescents and lowering the screening age to 45.

Why does this matter?

According to the American Cancer Society, colorectal cancer diagnoses in people under 50 in the US rose by 2.9% per year between 2013 and 2022, and colorectal cancer has become the leading cause of cancer-related loss of life in this age group. A similar rise is being seen in many countries in Europe, Australia and Asia. Young patients are often diagnosed at a more advanced stage, because neither patients nor doctors think of cancer first at this age, and symptoms are attributed to common problems such as hemorrhoids.

The rise is most often discussed in terms of diet, obesity, physical inactivity and the gut microbiota. But another question was also waiting for an answer: is the tumor that develops in young people biologically the same disease as the tumor in older people? As Kimmie Ng of Dana-Farber Cancer Institute puts it, survival in patients under 35 in particular may be no better than in patients in their 40s or 60s, despite more intensive treatment and better overall health. This strengthens the idea that the tumor itself may be different.

Is bowel cancer biologically different in young people?

The new findings suggest that at least some colorectal cancers that develop in young people may be biologically different. In the 189-tumor atlas published in Nature Medicine, younger patients' tumors showed more support cells, higher long non-coding RNA activity and cell communication linked to spread. However, it has not yet been proven that these differences cause the disease or a more aggressive course.

How was the study done?

Researchers from Dana-Farber Cancer Institute, Mass General Brigham and the Broad Institute (first author Caroline Porter; senior authors Ana C. Anderson, Kimmie Ng and Ramnik J. Xavier) analyzed tumors from 189 patients who had surgery at Brigham and Women's Hospital and whose tissue had been stored frozen. Of these patients, 54 were diagnosed before age 50 and 135 at age 50 or older. The method used was single-nucleus RNA sequencing (snRNA-seq), which also works on frozen tissue: the RNA in each cell nucleus is read separately to determine which genes are active, how active they are and which type the cell belongs to (what is RNA sequencing?).

The study has an important methodological difference: instead of splitting patients into "under 50" and "50 and over," the researchers looked for features that change gradually with age. Tumor location, stage, the patient's sex and whether the patient had received treatment before surgery were accounted for statistically. This was an attempt to remove some of the factors that had blurred the results of earlier, smaller studies.

Three main findings

1. More support cells in younger patients' tumors

A tumor is not made up of cancer cells alone; it is surrounded by a "microenvironment" of connective tissue cells (fibroblasts), blood vessels and immune cells. In the atlas, in the most common subtype of colorectal cancer, the ratio of support (stromal) cells to cancer cells was significantly higher in younger patients' tumors. This finding was also confirmed in a separate gene activity dataset of 564 tumors and by computer analysis of stained tissue images from 712 tumors. In other solid tumors, stroma-rich tumors have been found to be more resistant to chemotherapy; however, this study did not directly test for such resistance in colorectal cancer.

2. Higher "dark" RNA activity

Younger patients' tumors showed higher activity of long non-coding RNAs (lncRNAs), which do not make proteins but can regulate how genes work. Some of these RNAs appeared again and again across different types of cancer cells. The researchers emphasize that most of them are "dark" RNAs whose function is not yet known. For this reason, the finding is only a clue for now: what each RNA does in the tumor needs to be investigated in separate experiments.

3. Cell communication linked to spread

Cells "talk" to each other through signaling molecules and the receptors that recognize them. In younger patients' tumors, gene activity patterns suggested stronger cell-to-cell communication that could support cancer cells in moving and advancing into surrounding tissue. This is an inference drawn from gene activity; it has not been shown experimentally that the signals actually increase spread.

Why should the findings be interpreted with caution?

• Association, not cause: The atlas shows features that change with age; it does not prove that these features make cancer appear earlier or progress faster. The researchers themselves stress this point.
• Tissue from a single center: The main atlas comes from a single hospital biobank and from patients who were able to have surgery. Fifty-four young patients is a large number for single-cell research but a limited one for representing all young patients.
• Immune cells underrepresented: The method captured relatively few immune cells; this study cannot tell whether the immune response differs in young people.
• No link to survival: The relationship of the findings to treatment response or survival was not tested in this study.
• Causes not investigated: The link between these tumor features and factors such as diet-related chemicals and gut microbes needs to be examined separately.

So what is causing the rise in young people?

There is no definitive answer; most likely, several factors play a role together. The fact that the rise is most pronounced in later-born generations points to exposures that begin in childhood and adolescence.

• Lifestyle and diet: Obesity, physical inactivity, sugary drinks, red and processed meat and ultra-processed foods have been linked to increased risk (lifestyle and colorectal cancer).
• Gut microbiota: In a 981-genome study published in Nature in 2025, the mutational signature of colibactin, a toxin produced by some E. coli strains, was found 3.3 times more often in people diagnosed before 40 than in those diagnosed after 70; these mutations are thought to arise in the first decade of life (microbiota and colorectal cancer).
• Heredity: About 16% of patients diagnosed before 50, or roughly 1 in 6, carry an inherited gene change such as Lynch syndrome. For this reason, genetic counseling and genetic testing for inherited risk are recommended for every patient in this age group (hereditary cancers, germline variant analysis).
• Tumor biology: The new atlas offers a cell-level starting point for investigating what kind of mark the factors above may be leaving in the tumor.

Where does the tumor occur in young people, and with what symptoms?

Colorectal cancers in young people are more often located on the left side of the large bowel (descending and sigmoid colon) and in the rectum. This is why rectal bleeding is one of the most common and most important symptoms. However, this symptom is often blamed on hemorrhoids, and diagnosis can be delayed for months (symptoms of colon and rectal cancer).

Unexplained iron deficiency is especially important in young men and in women who do not menstruate, and should be evaluated for blood loss from the bowel. A person with symptoms may need a colonoscopy without waiting until screening age.

What can we do today?

The atlas does not immediately change treatment or screening; but it shows once again that colorectal cancer in young people is a real problem that deserves separate attention. For now, the evidence-based steps are:

• If you are at average risk, talk with your doctor about starting screening at age 45 (screening with colonoscopy, alternatives to colonoscopy).
• People with a first-degree relative who had colorectal cancer or an advanced polyp should start screening earlier, usually at age 40 or 10 years before the age at which the relative was diagnosed (polyps).
• If a fecal occult blood test (FIT) comes back positive, do not postpone colonoscopy (what to do after a positive test).
• If you have rectal bleeding, a change in bowel habits or unexplained iron deficiency, see a doctor whatever your age.
• If you were diagnosed with colorectal cancer before 50, ask for genetic counseling and genetic testing for inherited risk; the result also matters for your family.
• A healthy weight, regular physical activity, a diet rich in fiber and low in processed foods, and avoiding smoking and alcohol lower the risk (foods that lower risk, obesity and healthy diets).

Frequently Asked Questions

Why is bowel cancer rising in young people?

The exact cause is not known. Obesity, physical inactivity, processed foods, the gut microbiota (e.g., colibactin-producing bacteria), heredity and early-life exposures may all play a role together. The fact that the rise is most pronounced in later-born generations points to factors that begin in childhood and adolescence.

Is bowel cancer in young people biologically different?

New findings suggest that it may be. In a 189-tumor single-cell atlas, tumors of the most common subtype in younger patients showed more support cells, higher long non-coding RNA activity and cell communication linked to spread. Whether these differences affect the course of the disease is not yet known.

What are the symptoms of colorectal cancer in young people?

The most common symptoms are rectal bleeding, a change in bowel habits (diarrhea, constipation, narrow stools), persistent abdominal pain and unexplained iron-deficiency anemia. If these symptoms last longer than a few weeks, see a doctor regardless of age.

At what age should I start colon cancer screening?

US guidelines recommend age 45 for people at average risk; in Türkiye, the national program covers ages 50–70. For people with a family history of colorectal cancer or advanced polyps, screening usually starts at age 40 or 10 years before the age at which the relative was diagnosed.

Glossary

Early-onset colorectal cancer

Colon or rectal cancer diagnosed before age 50.

Single-nucleus RNA sequencing (snRNA-seq)

A method that reads the RNA in each cell nucleus separately to determine cell type and gene activity; it can also be used on frozen tissue.

Cell atlas

A detailed map showing all the cell types in a tissue and their characteristics.

Tumor microenvironment

All the support cells, blood vessels, immune cells and connective tissue surrounding cancer cells.

Stromal (support) cell

Cells in a tumor that are not cancer cells and that form connective tissue and blood vessel structures; the most important are fibroblasts.

Long non-coding RNA (lncRNA)

Long RNA molecules that do not make proteins but can regulate how genes work.

Birth-cohort effect

Higher disease risk at the same age in later-born generations.

Colibactin

A bacterial toxin produced by some E. coli strains that leaves a distinctive mutational signature in DNA.

Lynch syndrome

The most common hereditary colorectal cancer syndrome, which raises the risk of many cancers, especially colorectal and uterine cancer.