To address the rise in early-onset colorectal cancer, researchers led by the University of California San Diego have identified colibactin, a toxin produced by specific strains of Escherichia coli, as a potential culprit. Colibactin, which alters DNA, imprints distinct mutational signatures on colon cells, increasing the likelihood of colorectal cancer in individuals under 50.

A study published in *Nature* analyzed 981 colorectal cancer genomes from patients across 11 countries with varying cancer risks. It revealed that colibactin-associated DNA mutation patterns are 3.3 times more common in patients under 40 compared to those diagnosed over 70.

 These mutations were especially prevalent in regions with higher early-onset colorectal cancer cases. Senior author Ludmil Alexandrov described these mutational patterns as a "historical record," highlighting early-life exposure to colibactin as a contributing factor to early-onset disease.

Colibactin-related mutations are believed to arise during the first 10 years of life. These early genetic alterations, including APC driver mutations that directly promote tumor growth, potentially accelerate colorectal cancer development by decades.

The implications of this research are significant as early-onset colorectal cancer rates have doubled every decade for the past 20 years. It is now a growing public health concern in at least 27 countries. The disease is projected to become the leading cause of cancer-related deaths among young adults by 2030. Many cases lack known risk factors such as obesity or family history, which has fueled speculation about environmental or microbial exposures.

This study is part of the broader work of the Cancer Grand Challenges team Mutographs, which specializes in identifying mutational signatures left by environmental factors and behaviors. Their findings suggest that microbial exposure to colibactin-producing bacteria in childhood may silently initiate DNA damage, setting the stage for colorectal cancer. However, researchers emphasize the need for further investigation to establish causality.

To mitigate risks, the team is exploring how children are exposed to colibactin-producing bacteria, whether probiotics can eliminate harmful strains, and how stool sample tests might detect colibactin-related mutations for early intervention. Additionally, they are studying regional environmental factors that may contribute to cancer risk, with countries like Argentina, Brazil, and Thailand showing distinct mutational patterns.

This research redefines the understanding of cancer, suggesting that environmental and microbial factors in early life may play a key role in disease onset. The team remains committed to global prevention strategies and early detection methods to combat rising colorectal cancer rates.