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Reading 981 bowel cancer genomes from 11 countries found that the fingerprint of colibactin, a DNA-damaging toxin made by some gut bacteria, is more than three times as common in people diagnosed under 40 as over 70, and is stamped on the tumour early in life. It is the strongest lead yet on why bowel cancer is rising in young adults.
Díaz-Gay, Dos Santos, Moody and colleagues examined 981 colorectal cancer genomes from 11 countries to ask whether mutational processes contribute to geographic and age-related differences in incidence. 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 aetiologies, varied in prevalence across 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, were enriched in early-onset cancers and were imprinted early during tumour development. Colibactin exposure was further linked to APC driver mutations.
If a childhood exposure to colibactin-producing Escherichia coli writes APC mutations into the colon decades before a tumour appears, then the rise in early-onset bowel cancer may be preventable by something done in childhood rather than by screening alone.
One of the few modifiable exposures with a plausible adolescent window to match the birth-cohort pattern; it is the kind of hypothesis a cohort can generate but not settle.
The paper that turned early-onset colorectal cancer from an anecdote into a policy problem, and the direct evidence behind lowering the screening start age from 50 to 45 in the United States.
Shares Increasing incidence of colorectal cancer in young adults in Europe over the last 25 years, Colorectal cancer incidence patterns in the United States, 1974-2013, Find out what is driving early-onset bowel cancer, starting with colibactin, before extending screening any further, Early-onset colorectal cancer (under 50) and the tag colorectal-evidence.
Shares Colorectal cancer incidence patterns in the United States, 1974-2013, Early-onset colorectal cancer (under 50), The hardest cancers are found late, Colorectal cancer roadmap: from the adenoma-carcinoma sequence and the first screening trials to total mesorectal excision, oxaliplatin, RAS testing, immunotherapy for mismatch repair-deficient disease, ctDNA-guided treatment and organ preservation and the tag colorectal-evidence.
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Shares APC, Prevention we already have is not deployed, The hardest cancers are found late, Colorectal cancer roadmap: from the adenoma-carcinoma sequence and the first screening trials to total mesorectal excision, oxaliplatin, RAS testing, immunotherapy for mismatch repair-deficient disease, ctDNA-guided treatment and organ preservation and the tag colorectal-evidence.
Shares APC, Nature, Whole-exome & whole-genome sequencing, Colorectal cancer roadmap: from the adenoma-carcinoma sequence and the first screening trials to total mesorectal excision, oxaliplatin, RAS testing, immunotherapy for mismatch repair-deficient disease, ctDNA-guided treatment and organ preservation and the tag colorectal-evidence.
Shares Prevention we already have is not deployed, The hardest cancers are found late, Colorectal cancer roadmap: from the adenoma-carcinoma sequence and the first screening trials to total mesorectal excision, oxaliplatin, RAS testing, immunotherapy for mismatch repair-deficient disease, ctDNA-guided treatment and organ preservation, Colorectal cancer and the tag colorectal-evidence.
Shares Early-onset colorectal cancer (under 50), Prevention we already have is not deployed, The hardest cancers are found late, Colorectal cancer roadmap: from the adenoma-carcinoma sequence and the first screening trials to total mesorectal excision, oxaliplatin, RAS testing, immunotherapy for mismatch repair-deficient disease, ctDNA-guided treatment and organ preservation and the tag colorectal-evidence.
Shares Prevention we already have is not deployed, The hardest cancers are found late, Colorectal cancer roadmap: from the adenoma-carcinoma sequence and the first screening trials to total mesorectal excision, oxaliplatin, RAS testing, immunotherapy for mismatch repair-deficient disease, ctDNA-guided treatment and organ preservation, Colorectal cancer and the tag colorectal-evidence.