Early-Onset Colon Cancer: New Research on Causes

A concerning rise in early-onset colon cancer among young, fit adults has prompted researchers to investigate causes beyond traditional risk factors. Virginia-based doctor Tim Cannon observed a cluster of aggressive cases in endurance athletes, leading to a study where 39% of runners had precancerous colon tumors.

Researchers are now looking at early life as a critical window. UC San Diego scientist Ludmil Alexandrov identified a mutational signature caused by colibactin, a toxin from E. coli, often affecting infants before nine months. Experts like Dr. Kimmie Ng emphasize the role of the microbiome, while others note the impact of modern diets high in sugar and low in fiber.

Factors such as birth method (C-section vs. vaginal) and breastfeeding are also under scrutiny. While lifestyle changes like increasing fiber and reducing sugar are recommended, the scientific consensus is that these cancers result from complex interactions between genetics, environment, and early-life exposures.

Five years ago, Tim Cannon, a cancer doctor in Virginia, noticed a disturbing trend: his colon cancer patients were getting younger and their disease was more aggressive. Within a six-month period, he diagnosed three people in their 30s with late-stage, metastatic cancer. "Within a six-month period, I saw three extreme athletes in their 30s with metastatic, very advanced, incurable colon cancer," Cannon said. All three were endurance athletes, and tragically, all three patients died.

Cannon suspected this pattern was not an anomaly. He examined 100 long-distance runners between 35 and 50 years old. The results were startling: 39 had developed precancerous tumors in their colons. Fifteen of those cases were advanced, a rate far exceeding the expected 1.2%. This meant nearly one-sixth of the runners were at immediate risk.

This early research points to broader questions confounding the medical community: Why are young, fit adults getting sick from colon and rectal cancer? And why are patients under 45—the age when screening typically begins—developing the most aggressive forms of the disease?

As researchers scramble for answers, attention has shifted to the first year of life. Dr. Kimmie Ng, director of Dana-Farber's Young-Onset Colorectal Cancer Center, notes, "The steepest rise is in people in their 20s and 30s." She adds, "They're younger, they're healthier, they don't have comorbidities, they get more treatment — and yet they're not living longer."

At UC San Diego, molecular biologist Ludmil Alexandrov published a study in Nature identifying a mutational signature in more than half of colorectal tumors found in patients under 40. This signature appears to be caused by colibactin, a toxin produced by a specific strain of E. coli. What startled researchers was the timing: the infection occurred before babies reached their ninth month of life.

Alexandrov's research suggests infants can acquire DNA mutations months into life, predisposing them to cancer decades later. "You get your first hit at age 1 instead of age 30," Alexandrov said. "So you are about 20 to 30 years ahead of schedule for cancer." He warns that "Something that happened at age 6 months, you don't even consider when you're 35. That disconnect is extremely problematic."

The rise in early-onset cases is likely multifactorial. Dr. Maria Gloria Domínguez-Bello, a professor at Rutgers University, states, "There is strong evidence that early-life microbial disruption can influence long-term health risk." Modern changes to birth and feeding practices may disrupt the infant microbiome. Babies born vaginally acquire critical microbes from the mother, while C-section babies start with different microbial communities.

Diet plays a significant role. Dr. Andrea Cercek at Memorial Sloan Kettering noticed high sugar consumption stood out among her youngest stage 4 patients. "There were slight differences in risk factors — and sugars in particular," Cercek said. Dr. Stephen O'Keefe emphasizes that "A high fiber diet produces metabolites that suppress colon cancer risk," while "A high saturated meat diet produces metabolites that are inflammatory and carcinogenic."

Other modern factors include:

• Artificial light at night disrupting DNA repair
• Long periods of sitting slowing gut motility
• Air pollution introducing carcinogenic particles

Dr. Heinz-Josef Lenz at USC suggests these factors may trigger epigenetic changes, influencing cancer risk regardless of genetics.

If early life is the root cause, prevention strategies must start there. Alexandrov envisions targeted probiotics for infants to neutralize colibactin-producing bacteria. "If we can monitor the mutations and see that the ones exposed to the probiotic don't appear," he said, "it could mean we're eliminating the cause."

Researchers are also exploring "vaginal seeding" for C-section babies to transfer maternal microbes, though results will take years. The infant formula market is evolving, with companies developing products containing synthetic versions of complex sugars found in breastmilk to mimic a breastfed microbiome.

Regarding treatment, Dr. Steve Kay and Dr. Lenz are investigating the circadian rhythm. They found that drugs targeting circadian clock proteins could kill colorectal cancer cells. Despite these advances, oncologists caution that behavior changes reduce risk but do not eliminate it. As Cannon notes, "You don't have total control over this, as far as I can tell."