Colorectal cancer rates have been steadily increasing in younger adults in recent decades – a phenomenon that has gone largely unexplained.
A toxin produced by certain strains of bacteria — in particular E. coli — may be to blame, according to a study out of the University of California, San Diego.
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Colorectal cancer diagnoses in people 18 to 50 have increased 15% since 2004, compared to a 3% rise in diagnoses in people 45 to 55 during the same time period, according to the National Cancer Database.
Colorectal cancer is now the leading cause of cancer death in men younger than 50 and the second leading-cause of cancer death for women under 50. In the late 1990s, colorectal cancer was the fourth-leading cause of cancer deaths for both men and women under 50, according to the American Cancer Society.
Often, young people diagnosed with colorectal cancer have no family history of the disease or risk factors such as obesity and high blood pressure.
Colorectal cancer starts in the colon, or in the rectum. Usually, it begins as clusters of cells called polyps that then grow and transform into cancer.
The rapid rise in early-onset colorectal cancer is "remarkably striking," Dr. James T. McCormick, a colorectal surgeon and chair of the Pennsylvania chapter of the American College of Surgeons Commission on Cancer, told the Colorectal Cancer Alliance last year. "We're not quite sure why that's happening or how to screen for it at such a young age. That's the conundrum."
The mystery seems to have been partly solved by the new research that found a toxin called colibactin causes genetic mutations far more frequently in colorectal cancer found in people under 40 compared to in colorectal cancer in people diagnosed after age 70. The research, published Wednesday in the journal Nature, also found that these patterns of mutations were "particularly prevalent" in countries that have high rates of colorectal cancer in young people.
A 2024 study showed that early-onset colorectal cancer was on the rise in at least 27 countries.
"When we started this project, we weren't planning to focus on early-onset colorectal cancer," said Marcos Díaz-Gay, one of the UC San Diego researchers. "Our original goal was to examine global patterns of colorectal cancer to understand why some countries have much higher rates than others. But as we dug into the data, one of the most interesting and striking findings was how frequently colibactin-related mutations appeared in the early-onset cases."
Childhood exposure to colibactin seems to account for about 15% of the mutations in the colon that drive the development of colorectal cancer, according to the study.
"If someone acquires one of these driver mutations by the time they're 10 years old, they could be decades ahead of schedule for developing colorectal cancer, getting it at age 40 instead of 60," the study's senior author Ludmil Alexandrov said.
But how children are being exposed to colibactin-producing bacteria and what can be done to prevent infection needs further study, Alexandrov said.
The results of the study reshape "how we think about cancer," Alexandrov said. "It might not be just about what happens in adulthood — cancer could potentially be influenced by events in early life, perhaps even the first few years. Sustained investment in this type of research will be critical in the global effort to prevent and treat cancer before it's too late."