New research has found a potential microbial culprit behind the alarming rise in early-onset colorectal cancer
Exposure to colibactin, a toxin produced by certain strains of the bacterium, Escherichia coli, in early childhood may increase the risk of developing colorectal cancer before the age of 50, new research suggests.
Researchers from the Wellcome Sanger Institute, University of California San Diego and their collaborators analysed 981 colorectal cancer genomes from patients with both early- and late-onset cancer across 11 countries with varying colorectal cancer risk levels.
The new study, published today (23 April) in Nature, reports that exposure to colibactin in early childhood imprints a distinct pattern of change, known as the “mutational signature”, on the DNA of colon cells — one that may increase the risk of developing colorectal cancer before the age of 50.
Despite overall colorectal cancer cases decreasing, this particular cancer is on the rise amongst young people in at least 27 countries.1 If current trends continue, colorectal cancer is projected to become the leading cause of cancer-related deaths among young adults globally by 2030.
Until now, the reasons behind this surge have remained unknown. Young adults diagnosed with colorectal cancer often have no family history of the disease and few known risk factors such as obesity or hypertension. This has fueled speculation about potential hidden environmental or microbial exposures that are contributing to cases, especially in young adults.
This current study originally sought to understand the variation of colorectal cancer incidences between countries by sequencing colorectal cancer genomes from 11 countries on four continents to understand how changes in DNA contribute to geographic and age-related differences in cancer rates.2 However, when analysing the data, the researchers revealed interesting findings about the early-onset cases in particular.
The findings show that colibactin, a toxin produced by E. coli, leaves behind specific patterns of DNA mutations that were 3.3 times more common in early-onset cases – specifically in adults under 40 – than in those diagnosed after the age of 70. These mutation patterns were also particularly prevalent in countries with high incidence of early-onset cases.
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.
Dr Marcos Díaz-Gay
co-first author and Junior Group Leader at the Spanish National Cancer Research Centre
Credit: Welcome Sanga Institute