Scientists uncover how cancer time bombs are silently planted in children by their own guts

Scientists have identified a bacterial toxin that may be playing a role in the rising cases of colorectal cancer among young adults. A team led by the University of California, San Diego, working with researchers from 11 countries, has found evidence suggesting that colibactin—a toxin produced by certain strains of Escherichia coli—can cause DNA damage that might lead to cancer before the age of 50. Their findings were published in Nature.

To better understand why colorectal cancer is becoming more common in younger individuals, researchers examined 981 cancer genomes from patients across different parts of the world. Their analysis showed that cancers with unstable DNA did not vary much between countries. However, microsatellite-stable cancers displayed notable differences in mutation patterns and mutation burdens.

Certain DNA mutations were more frequent in Argentina, Brazil, Colombia, Russia, and Thailand, indicating that local environmental or microbial exposures might be playing a role. The bacterial toxin colibactin was found more often in places with higher colorectal cancer rates, further reinforcing its potential significance.

Lead researcher Ludmil Alexandrov explained that mutation patterns found in cancer genomes act like a historical record, showing early-life exposure to colibactin as a possible factor contributing to early-onset disease.

The study found that two specific mutation patterns—SBS88 and ID18—associated with colibactin were found 3.3 times more often in patients diagnosed before age 40 than in those diagnosed after age 70. The toxin was also linked to mutations in the APC gene, which plays a major role in tumor development. In cases where colibactin exposure was confirmed, about 25% of APC gene mutations resulted from ID18-related DNA changes.

For those unfamiliar, the APC (Adenomatous Polyposis Coli) gene is a tumor suppressor gene that plays a crucial role in regulating cell growth and division, thus helping to deal with abnormalities like tumors and cancer.

Scientists believe exposure to colibactin-producing bacteria may occur early in life, possibly even during childhood, leading to small DNA mutations that could eventually increase cancer risk decades later. Alexandrov noted that if someone acquires one of these early mutations by the time they are 10 years old, they may end up developing colorectal cancer much earlier than expected, potentially by age 40 instead of 60.

The number of younger adults diagnosed with colorectal cancer has doubled in many countries over the past 20 years, yet researchers still don’t fully understand why. Unlike older patients, younger individuals diagnosed with this disease often lack common risk factors such as obesity or a family history of colorectal cancer. This has led scientists to explore hidden environmental or microbial causes, with colibactin now a major suspect.

Researchers are now investigating several key questions, including how people are exposed to colibactin-producing bacteria, whether certain lifestyles or diets increase exposure, and whether probiotics can safely remove harmful bacteria. This study is part of a larger effort by the Cancer Grand Challenges team Mutographs, which has examined DNA mutation patterns in various cancers affecting the esophagus, kidneys, and head and neck.

However, future research could face funding challenges. Much of the work relies on support from the U.S. National Institutes of Health, but proposed budget cuts could put critical projects at risk. Alexandrov emphasized that if NIH funding cuts disrupt this research, it could negatively impact cancer studies worldwide.

Scientists hope continued funding will allow them to develop effective prevention strategies for early-onset colorectal cancer. They also suspect many cancers may start much earlier in life than previously thought, challenging existing views on when the disease begins. Alexandrov noted that this research reshapes the understanding of cancer, suggesting that environmental exposures or microbial influences in early childhood could play a significant role in cancer development later in life.

Source: University of California, Nature

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