Childhood exposure to a bacterial toxin produced in the bowel may be driving an increase in colorectal cancer among young people, a new study has found.
The findings are the latest evidence on what’s driving a global rise in early-onset cancers.
Once thought of as a disease of ageing, scientists have been racing to understand why more people under age 50 are getting cancer.
Worldwide, the number of early-onset cancer diagnoses has surged by about 80 per cent since 1990, while deaths have risen by 28 per cent, according to a 2023 study. Prostate and nasopharyngeal, or throat-related, cancers have seen the sharpest increases in incidence.
It’s not entirely clear why, but researchers believe the uptick is driven by a combination of environmental and lifestyle factors that trigger mutations to our genes, raising the risk of certain cancers.
The new analysis, published in the journal Nature on Thursday, suggests that for colorectal cancer, the answer lies partly with childhood exposure to a bacterial toxin called colibactin.
Colibactin is made by a certain strain of E. coli, a common gut microbe that lives in the intestine or bowel.
Exposure in early childhood appears to leave a unique genetic fingerprint on colon cells, raising the risk that someone will develop colorectal cancer before they turn 50, the study found.
Colibactin-linked gene mutations
“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,” Ludmil Alexandrov, the study’s senior author and a professor of cellular and molecular medicine at the University of California San Diego, said in a statement.
Researchers analysed samples from 981 colorectal cancer patients in 11 countries. They found that colibactin-linked gene mutations were 3.3 times more common in cancer patients under 40 compared with those diagnosed after the age of 70.
In countries where early-onset colorectal cancer is more common, the mutations were even more prevalent, the study found.
Notably, the gene changes emerged early on as people’s tumours grew, in line with previous research that indicates mutations happen within the first 10 years of life.
That means the bacteria could be setting the stage for cancer in young children, decades before they develop symptoms, the researchers said.
“This reshapes how we think about cancer,” Alexandrov said. “It might not be just about what happens in adulthood – cancer could potentially be influenced by events in early life, perhaps even the first few years”.
Study limitations
Independent experts said more studies are needed to confirm that colibactin-linked mutations do cause colorectal cancer, as well as how children are being exposed to the bacteria.
“It’s not clear when and how the particular strain of E. coli gets into the bowel in the first place, and why they are usually gone again by the time the cancer starts to grow,” Trevor Graham, who leads the Centre for Evolution and Cancer at The Institute of Cancer Research in the UK, said in a statement.
Questions also remain about how the bacteria could be eliminated – and whether doing so could have unintended consequences for gut health, given E. coli bacteria are used in some probiotics, he added.
Many more people could be exposed to colibactin without getting cancer, he said.
“I think it is very likely cancer only occurs in some cases, because even though someone might have the ‘bad bugs’ that cause mutations, those bugs have to cause the right mutations to make a cancer grow,” Graham said.
