An international research team led by the University of California, San Diego, has published a study in the journal Nature, linking childhood exposure to a bacterial toxin called colibactin to the rising incidence of colorectal cancer among young adults. The findings suggest that early-life exposure to colibactin, produced by certain strains of Escherichia coli (E. coli), may accelerate the development of colorectal cancer decades earlier than traditionally observed.
Colorectal cancer, long considered a disease of old age, is increasingly affecting people in their 20s, 30s, and 40s in countries like the United States and the United Kingdom, a phenomenon that has puzzled doctors. According to NBC News, two years ago, the American Cancer Society reported that colorectal cancer diagnoses in patients under 55 had doubled between 1995 and 2019.
Despite this alarming trend, the reasons for the increase in colorectal cancer among younger people remained largely unknown. The new study points to exposure during childhood to colibactin-producing E. coli as a possible explanation. Colibactin is a toxin capable of altering DNA and inflicting distinct damage on colon cells, potentially increasing the risk of developing colorectal cancer before the age of 50.
The researchers examined 981 colorectal cancer genomes from patients in 11 countries, including the United States and the United Kingdom, focusing on both early- and late-onset disease. They discovered that mutations associated with colibactin were 3.3 times more frequent in the tumors of younger patients under 40 compared to those over 70. These mutation patterns were particularly prevalent in countries with a high incidence of early-onset colorectal cancer cases, suggesting possible specific environmental exposures.
"These mutational signatures are a kind of historical record in the genome," said Professor Ludmil Alexandrov at the University of California, San Diego. "They point to the fact that exposure to colibactin in early stages of life favors early-onset colorectal cancer."
The study's first author, Spanish researcher Dr. Marcos Díaz-Gay, who completed his doctoral studies at the University of California, San Diego, and currently directs the Digital Genomics Group at the Spanish National Cancer Research Centre (CNIO), noted the significance of the findings. "As we delved into the data, one of the most interesting and striking findings was the frequency with which mutations related to colibactin occurred in early-onset cases," he said, according to EurekAlert.
The researchers found that the harmful effects of colibactin begin early, with especially detrimental effects in infants. They dated the origin of these mutations to the first ten years of the patients' lives, long before the tumor was detectable. "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," added Alexandrov.
Young adults diagnosed with colorectal cancer often present few known risk factors, such as obesity or hypertension, and many do not have a family history of the disease. This lack of known risk factors has led researchers to search for possible causes among environmental carcinogens or microbial infections. The identification of colibactin-producing E. coli strains as a potential culprit sheds new light on this medical mystery.
Colibactin-producing bacteria can silently colonize the intestines of children, possibly through contaminated water or food. While E. coli is important for maintaining a healthy gut microbiome, some strains can produce colibactin, which is capable of altering DNA and has been linked to colorectal cancers for more than two decades.
The study provides a direct association between colibactin and specific patterns of DNA mutations found in early-onset colorectal cancer cases. These findings open new avenues for early detection and prevention strategies. The research team is developing noninvasive tests that analyze stool samples for colibactin-related mutations, which could help detect genetic signatures related to colibactin before tumors appear.
"This reshapes 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." He cautioned that while the findings provide strong support for the hypothesis, further research is necessary to establish causality.
The implications of this work suggest that early-life exposure to certain microbial toxins may have long-term consequences for cancer development. Scientists are exploring preventive approaches, such as targeted probiotics or vaccines, to eliminate dangerous bacterial strains and reduce the risk in exposed children.
"Understanding the traces left by bacteria, toxins, or lifestyle habits in the genome can be key to anticipating, preventing, and treating cancer," remarked Díaz-Gay. The discovery opens the door to expanding research in other fields, with new projects already underway, aimed at advancing toward more predictive and personalized medicine.
The article was written with the assistance of a news analysis system.