Scientists investigating an alarming rise in bowel cancer in young adults have identified the bacterial toxin colibactin as a potential culprit, with childhood exposure perhaps increasing the risk of later cancer development.
Colibactin has already been linked to this cancer type, but the relationship hasn't been specifically studied in people under the age of 50 before. It may go some way to explaining why bowel (or colorectal) cancer is on course to be the leading cancer-related cause of death in young adults in the next few years.
Analyzing cancer tissue samples from 981 individuals across 11 countries, an international team of researchers looked for cancer-causing mutations in the DNA genome. In more than half of the early-onset cases, these mutations matched up with damage caused by colibactin.
"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," says computational biologist Ludmil Alexandrov of the University of California San Diego.
So how is this exposure happening? The researchers aren't sure, but we do know that colibactin is produced by certain strains of Escherichia coli in the gut, and the data suggests that the damaging exposure probably happens in the first 10 years of life.
One of the more likely scenarios is that childhood infections are producing colibactin, which then damages DNA in the bowel. These harmful mutations then make cancer more likely later on, typically long after the colibactin has disappeared.
Specifically, colibactin-related DNA mutations were 3.3 times more common in adults diagnosed under the age 40, compared to those diagnosed at age 70 or above. For cancer in older people, the DNA patterns were more often associated with normal aging.
"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," says Alexandrov.
Previous research has identified several associations that could be contributing to the rise in colorectal cancer at a relatively young age. Studies have pointed to ultra-processed food, and too many sugary or alcoholic beverages, for example.
Here, the suggestion is that lifestyle or environmental factors very early on in life may also be planting seeds of the disease. Further research is needed to know for sure, though with recent science funding cutbacks in the US, that research is by no means guaranteed.
The researchers also want to take a closer look at how colibactin and its related DNA scars could be protected against, as well as how the different factors affecting this kind of cancer risk may vary between countries.
"It's possible that different countries have different unknown causes," says computational biologist Marcos Díaz-Gay of the Spanish National Cancer Research Center. "That could open up the potential for targeted, region-specific prevention strategies."
The research has been published in Nature.