A toxin produced by E. coli may be driving rates of bowel cancer in young people, scientists have discovered.
Experts believe the finding could help explain why rates of bowel cancer are rising among young people across the globe.
The bacterial toxin – called colibactin – is capable of altering DNA and is produced by a strain of E. coli, though not the strain linked to infection such as diarrhoea in some people.
Researchers, including from the UK and backed by Cancer Research UK, found that exposure to colibactin in early childhood imprints a genetic signature on the DNA of bowel cells, which may then increase the risk of developing bowel cancer before the age of 50.
A previous study published in December found rates of bowel cancer in young people are rising more sharply in England than in many other countries around the world.
For those aged 25 to 49, England is among the countries with the biggest rise, averaging a 3.6% increase every year in the decade up to 2017.
Data provided by Cancer Research UK up to 2019 further suggests that bowel cancer has seen a 52% increase in incidence rates for adults aged 25 to 49 since the early 1990s.
There are around 2,600 new bowel cancer cases in people aged 25-49 in the UK every year and around 44,100 new cases among all ages.
Work has been ongoing to discover why more younger people are developing bowel cancer, with experts believing poor diet, more ultra-processed foods, obesity and a lack of exercise are playing a role.
Now in the latest study, led by the University of California San Diego (UCSD) and published in the journal Nature, researchers have uncovered another possible culprit.
Experts examined 981 colorectal (bowel) cancer genomes from patients with both early and late-onset disease in 11 different countries.
They found colibactin can leave behind specific patterns of DNA mutations that are 3.3 times more common in early-onset bowel cancer cases (in the study this was adults under 40) than in those diagnosed after the age of 70.
These mutation patterns were also particularly common in countries with a higher rate of early-onset bowel cancer.
Senior author, Ludmil Alexandrov, a professor at UCSD, said: “These mutation patterns are a kind of historical record in the genome, and they point to early-life exposure to colibactin as a driving force behind early-onset disease.”
Study first author Marcos Diaz-Gay, a former postdoctoral researcher, said: “When we started this project, we weren’t planning to focus on early-onset colorectal cancer.
“Our original goal was to examine global patterns of colorectal cancer to understand why some countries have much higher rates than others.
“But as we dug into the data, one of the most interesting and striking findings was how frequently colibactin-related mutations appeared in the early-onset cases.”
The study also found that colibactin-related mutations account for around 15% of what are known as APC driver mutations – some of the earliest genetic alterations that directly promote cancer development – in bowel cancer.
“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,” Professor Alexandrov said.
The work is part of Cancer Grand Challenges team Mutographs, funded by Cancer Research UK.
Researchers are now developing early detection tests that analyse stool samples for colibactin-related mutations.
The director of Cancer Grand Challenges, Dr David Scott, said: “Globally and in the UK, we’re witnessing an alarming increase in some types of cancer in people under the age of 50.
“It is unlikely that there will be one clear driver but Cancer Grand Challenges scientists are racing to solve this puzzle, and our Mutographs team has uncovered a surprising clue.
“Many early-onset colorectal cancer patients appear to have been exposed to a toxin, called colibactin, produced by some strains of the bacteria E. coli in early life.
“It’s unclear how the exposure originates, but we suspect that a combination of factors – including diet – may intersect during a crucial phase in the development of the gut microbiome.
“This study adds an important piece to the puzzle of early-onset cancers, but it isn’t conclusive, and more research will be needed to establish a definitive link between colibactin and an increased risk of early-onset colorectal cancer.
“Other Cancer Grand Challenges teams, like Optimisticc and Prospect, are looking deeper into the microbiome and other environmental factors to uncover what’s behind the global rise.”
Professor Sir Mike Stratton, Mutographs team lead and senior group leader at the Wellcome Sanger Institute, said: “Our research has allowed us to generate the hypothesis that the presence of colibactin leads to an increased number of mutations in colon cells, which then causes a greater risk of colorectal cancer at an early age.
“If this turns out to be correct, we can explore preventive measures such as tests that tell us if the toxin, or the bacterium that makes it, is present, and finding ways to eliminate them from our bodies at a young age.
“We know that diet and lifestyle choices drive the risk of developing colorectal cancer, but this study has opened up a new and exciting route we can take when researching how to lower the rate of early-onset colorectal cancer.”
