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Apr 25 2025
2A groundbreaking study has identified a strong link between early-onset colorectal cancer (CRC) and childhood exposure to a harmful toxin produced by gut bacteria. The findings shed light on why CRC rates are increasing among individuals younger than 50, with scientists uncovering distinct genetic signatures that trace back to early life.
The global rise in CRC cases among younger adults has prompted researchers to investigate environmental and lifestyle-related risk factors that might contribute to the trend. While genetics play a role, the new study emphasizes how early exposures can leave lasting marks on DNA. These imprints, called mutational signatures, provide a molecular history of environmental insults to the genome.
Leading the research is Dr. Ludmil Alexandrov, a cancer geneticist at the University of California, San Diego. By merging traditional epidemiology with genetic analysis, Alexandrov and his team examined whole-genome sequencing data from over 900 colorectal cancer patients spanning 11 countries across four continents. Their focus was on mutational patterns that could explain regional and age-related variations in CRC incidence.
The most notable discovery was a set of mutations linked to colibactin—a DNA-damaging toxin made by specific strains of Escherichia coli (E. coli), a common gut bacterium. While E. coli generally supports a healthy gut microbiome, certain strains produce colibactin, a compound capable of causing double-stranded breaks in DNA. This leads to two specific types of mutations: single base substitutions (SBS) and insertions or deletions (indels).
Earlier research had shown that colibactin-related mutations appeared in about 10 to 15 percent of all CRC cases. However, in the current study, these mutations—specifically SBS88 and ID18—were found to be 3.3 times more common in patients diagnosed before age 40 compared to those over 70.
“These mutation patterns act as a genomic diary, revealing exposure to colibactin early in life as a likely driver of early-onset colorectal cancer,” said Alexandrov.
To determine when these mutations occurred, researchers distinguished between mutations present in all tumor cells (early clonal) and those found only in some cells (late clonal). The colibactin-related mutations were predominantly early clonal, indicating they likely developed in the early stages of tumor formation. Furthermore, these mutations often co-occurred with additional driver mutations that accelerate cancer progression.
“If a child acquires one of these cancer-promoting mutations by age 10, they might face colorectal cancer two decades earlier than expected,” Alexandrov noted.
He emphasized that the findings shift the timeline of cancer development, highlighting the importance of what happens in the earliest years of life. “Cancer prevention efforts need to start much earlier than we thought,” he said. “Continued support for research like this is essential in the fight to detect and treat cancer before it takes hold.”
Source:https://www.the-scientist.com/childhood-exposure-to-bacterial-toxin-tied-to-early-onset-colorectal-cancer-72952
This is non-financial/medical advice and made using AI so could be wrong.
