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An international team of researchers has identified a potential microbial culprit behind the alarming rise in early-onset colorectal cancer: a bacterial toxin called colibactin.
Scientists report that exposure to colibactin in early childhood imprints a distinct genetic signature on the DNA of colon cells--one that could significantly increase the risk of developing colorectal cancer before the age of 50. The study was led by an international team of researchers, headed by the University of California, San Diego. It was produced by certain strains of Escherichia coli that reside in the colon and rectum, colibactin is a toxin capable of altering DNA. The new study, published on April 23 in Nature, analysed 981 colorectal cancer genomes from patients with both early- and late-onset disease across 11 countries with varying colorectal cancer risk levels. The findings reveal that colibactin 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 a high incidence of early-onset cases. "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," said study senior author Ludmil Alexandrov, professor in the Shu Chien-Gene Lay Department of Bioengineering and the Department of Cellular and Molecular Medicine at UC San Diego. Although previous studies, including earlier work from Alexandrov's lab, have identified colibactin-related mutations in roughly 10 to 15 per cent of all colorectal cancer cases, those studies either focused on late-onset cases or did not distinguish between early- and late-onset disease. This latest study is the first to demonstrate a substantial enrichment of colibactin-related mutations specifically in early-onset cases. The implications are sobering. Once considered a disease of older adults, colorectal cancer is now on the rise among young people in at least 27 countries. Its incidence in adults under 50 has roughly doubled every decade for the past 20 years. If current trends continue, colorectal cancer is projected to become the leading cause of cancer-related death among young adults 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. That has fueled speculation about potential hidden environmental or microbial exposures--something this new study directly investigates. (ANI)
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