Childhood Exposure to E. coli Toxin Linked to Rise in Early-Onset Colorectal Cancer.

In a major step toward understanding the surge of colorectal cancer among young adults, a team of international researchers led by the University of California San Diego has identified a bacterial toxin—colibactin—as a likely contributor. This toxin, produced by specific strains of Escherichia coli (E. coli) living in the colon and rectum, appears to leave a permanent genetic imprint that could trigger cancer decades later.

Published on April 23 in Nature, the study examined the genomes of 981 colorectal cancer patients from 11 countries with varying cancer rates. Researchers discovered that the unique mutation patterns caused by colibactin were over three times more prevalent in early-onset colorectal cancer patients—specifically those under 40—compared to individuals diagnosed after age 70. These mutations were also disproportionately frequent in countries with high early-onset incidence.

“These mutation patterns act like a genetic time stamp, showing us that colibactin exposure likely happened early in life,” said lead researcher Ludmil Alexandrov, professor of bioengineering and cellular and molecular medicine at UC San Diego and member of the Moores Cancer Center.

This study marks the first comprehensive investigation to link colibactin-related mutations predominantly to early-onset cases. While previous studies had detected the toxin's genetic footprint in a minority of colorectal cancers, they often failed to distinguish between early- and late-onset disease. This new research clarifies that early-life exposure may set the stage for cancer development well before traditional risk factors emerge.

The findings are particularly striking given the ongoing global increase in colorectal cancer among individuals under 50. The incidence rate in this age group has doubled every decade for the past 20 years across at least 27 countries. If this trend persists, colorectal cancer could become the leading cause of cancer-related death among young adults by 2030.

Notably, many young patients lack a family history of the disease or common risk factors such as obesity or high blood pressure, prompting scientists to investigate hidden environmental or microbial contributors. This new study directly addresses that gap by identifying a biological agent that may silently initiate genetic changes during childhood.

“When we began analyzing global cancer genomes, we didn’t set out to study early-onset colorectal cancer specifically,” said co-first author Marcos Díaz-Gay, formerly of Alexandrov’s lab and now at the Spanish National Cancer Research Center. “But the data made it clear that colibactin-related mutations were much more common in early cases.”

The team used molecular timing techniques to determine when the mutations likely occurred. The results suggest that colibactin’s DNA damage happens early in life—often within the first ten years. Furthermore, the toxin appears responsible for about 15% of APC gene mutations, among the earliest known drivers of colorectal cancer.

“If a child develops one of these mutations by age ten,” Alexandrov explained, “they may be set on a trajectory to develop colorectal cancer decades earlier than expected.”

While the evidence strongly supports the role of colibactin in early-onset cases, the researchers caution that further investigation is needed to establish definitive causality. Ongoing efforts include exploring how children are exposed to colibactin-producing bacteria and whether lifestyle, diet, or environmental factors encourage bacterial colonization.

The team is also investigating if probiotics could reduce or eliminate harmful E. coli strains and is developing stool-based tests to detect colibactin-associated mutations early.

Beyond the link to colibactin, the study also observed varying mutation signatures across different countries, including Argentina, Brazil, Colombia, Russia, and Thailand. These findings suggest that local environmental factors may influence cancer risk, potentially paving the way for regional prevention strategies.

“This opens the door to understanding unique causes of cancer by country,” Díaz-Gay said. “And that could help us develop more effective, targeted prevention approaches.”

The broader implication, Alexandrov noted, is that cancer risk might be shaped not just by adult exposures but by events occurring as early as infancy.

“This changes our perspective on cancer’s origins,” he said. “Early-life exposures, even those that leave no immediate symptoms, may silently contribute to disease decades later. Continued investment in this research is essential if we are to stop cancer before it starts.”

Source:https://www.sciencedaily.com/releases/2025/04/250423120654.html

This is non-financial/medical advice and made using AI so could be wrong.