Rise in colorectal cancers in young people under age 50 linked to bacterial toxin

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"A bacterial toxin called colibactin could help explain the mysterious rise in colorectal cancers in young people globally. Researchers examined the genomes of almost 1,000 colorectal cancers and found that people who were diagnosed before the age of 40 were 3.3 times more likely to have mutational signatures related to colibactin than those diagnosed after the age of 70.

Colibactin is a toxin that Escherichia coli and other bacteria use to defend themselves against attack, but it also harms DNA. This study cannot demonstrate a causal link, but it does raise the possibility of screening for colorectal cancer by testing for high-risk bacteria in stool samples  ..."

From the abstract:

"Colorectal cancer incidence rates vary geographically and have changed over time. Notably, in the past two decades, the incidence of early-onset colorectal cancer, affecting individuals under the age of 50 years, has doubled in many countries.

The reasons for this increase are unknown.

Here, we investigate whether mutational processes contribute to geographic and age-related differences by examining 981 colorectal cancer genomes from 11 countries. No major differences were found in microsatellite unstable cancers, but variations in mutation burden and signatures were observed in the 802 microsatellite-stable cases.

Multiple signatures, most with unknown etiologies, exhibited varying prevalence in Argentina, Brazil, Colombia, Russia, and Thailand, indicating geographically diverse levels of mutagenic exposure.

Signatures SBS88 and ID18, caused by the bacteria-produced mutagen colibactin, had higher mutation loads in countries with higher colorectal cancer incidence rates.

SBS88 and ID18 were also enriched in early-onset colorectal cancers, being 3.3 times more common in individuals diagnosed before age 40 than in those over 70, and were imprinted early during colorectal cancer development.

Colibactin exposure was further linked to APC driver mutations, with ID18 responsible for about 25% of APC driver indels in colibactin-positive cases.

This study reveals geographic and age-related variations in colorectal cancer mutational processes, and suggests that early-life mutagenic exposure to colibactin-producing bacteria may contribute to the rising incidence of early-onset colorectal cancer."

Nature Briefing: Cancer

Geographic and age variations in mutational processes in colorectal cancer (no public access, but article above contains link to PDF)