{"entity":{"id":"idea-crc-early-onset-cause-hunt","kind":"idea","name":"Find out what is driving early-onset bowel cancer, starting with colibactin, before extending screening any further","aka":[],"tldr":"Bowel cancer in people under 50 is rising by 2 to 8 percent a year on both sides of the Atlantic and nobody knows why. The strongest lead is a toxin made by some gut bacteria whose damage signature is three times more common in young patients and is stamped on the colon early in life. If that is the cause, the fix is in childhood, not in a screening programme.","summary":"Siegel's age-period-cohort analysis of 490,305 United States cases showed that someone born around 1990 has double the colon cancer risk and quadruple the rectal cancer risk of someone born around 1950; Vuik found the same cohort pattern across 20 European countries, with incidence rising 7.9 percent a year in 20 to 29-year-olds. Neither study can say what changed. Diet, obesity, antibiotic exposure and the microbiome have all been proposed, and Hur's cohort found that each daily sugar-sweetened drink in adolescence carried a relative risk of 1.32, on 109 cases.\n\nThe 2025 genome study is the first mechanistic lead with a plausible timing. Across 981 colorectal cancer genomes from 11 countries, the colibactin signatures SBS88 and ID18 were 3.3 times more common in cancers diagnosed before 40 than after 70, were higher in countries with higher incidence, were imprinted early during tumour development and accounted for about 25 percent of APC driver indels in colibactin-positive cases. Colibactin is made by pks-positive Escherichia coli, which colonise in childhood, which would explain a birth-cohort effect that a screening programme cannot touch.","asOf":"2026-09-24","links":[{"label":"Díaz-Gay et al.: geographic and age variations in mutational processes (Nature 2025)","url":"https://europepmc.org/article/MED/40267983"},{"label":"Siegel et al.: colorectal cancer incidence patterns 1974-2013 (JNCI 2017)","url":"https://europepmc.org/article/MED/28376186"},{"label":"Vuik et al.: rising incidence in young adults in Europe (Gut 2019)","url":"https://europepmc.org/article/MED/31097539"}],"tags":["colorectal-evidence"],"related":["colorectal-roadmap","prevention-roadmap","iarc"],"cancers":["colorectal","early-onset-colorectal"],"sections":["prevention","early-detection"],"technologies":["wes-wgs","colorectal-screening"],"targets":["apc"],"drugs":[],"companies":[],"institutions":[],"pathways":["microbiome-tumour"],"terms":["gut-microbiome-diversity"],"trials":[],"people":[],"bottlenecks":["b-early-detection","b-prevention-adoption","b-translational-valley"],"keyPapers":["paper-diaz-gay-colibactin-geographic-age-mutational-processes-nature-2025","paper-siegel-colorectal-incidence-birth-cohort-jnci-2017","paper-vuik-early-onset-colorectal-europe-gut-2019","paper-hur-sugar-sweetened-beverages-early-onset-colorectal-gut-2021"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A measurable childhood exposure, of which colibactin-producing pks+ Escherichia coli colonisation is the leading candidate, accounts for a substantial share of the birth-cohort rise in early-onset colorectal cancer, and its mutational signature can be detected in normal colonic crypts decades before a tumour appears.","rationale":"The colibactin signature is enriched in the young, geographically patterned in line with incidence, written early in tumour development and directly implicated in APC driver formation. No other proposed exposure has a mechanism that acts at the right age, and no screening policy can prevent cancers whose driver mutations were written before adolescence.","test":"A prospective cohort with stored childhood stool and normal colonic biopsies linked to registry outcomes, plus signature analysis of normal crypts across age bands in an existing biobank; in parallel, a randomised trial of a pks+ Escherichia coli decolonisation or displacement strategy in carriers, with the SBS88 and ID18 crypt burden as the surrogate endpoint. Reject the hypothesis if crypt signature burden does not track birth cohort in the same direction as incidence.","maturity":"preclinical-evidence","actor":"research","cost":"large","horizonYears":8},"route":"/ideas/idea-crc-early-onset-cause-hunt/","neighbours":{"roadmap":[{"id":"prevention-roadmap","kind":"roadmap","name":"Cancer prevention roadmap: tobacco control and vaccines → biomarker-guided chemoprevention → interception in carriers","route":"/roadmaps/prevention-roadmap/"},{"id":"colorectal-roadmap","kind":"roadmap","name":"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","route":"/roadmaps/colorectal-roadmap/"}],"institution":[{"id":"iarc","kind":"institution","name":"International Agency for Research on Cancer (IARC / WHO)","route":"/institutions/iarc/"}],"cancer":[{"id":"colorectal","kind":"cancer","name":"Colorectal cancer","route":"/cancers/colorectal/"},{"id":"early-onset-colorectal","kind":"cancer","name":"Early-onset colorectal cancer (under 50)","route":"/cancers/early-onset-colorectal/"}],"section":[{"id":"early-detection","kind":"section","name":"Early Detection & Screening","route":"/fronts/early-detection/"},{"id":"prevention","kind":"section","name":"Prevention & Risk","route":"/fronts/prevention/"}],"technology":[{"id":"colorectal-screening","kind":"technology","name":"Colorectal cancer screening (colonoscopy, FIT, stool DNA, blood)","route":"/technologies/colorectal-screening/"},{"id":"wes-wgs","kind":"technology","name":"Whole-exome & whole-genome sequencing","route":"/technologies/wes-wgs/"}],"target":[{"id":"apc","kind":"target","name":"APC","route":"/targets/apc/"}],"pathway":[{"id":"microbiome-tumour","kind":"pathway","name":"Microbiome-tumour interactions","route":"/pathways/microbiome-tumour/"}],"term":[{"id":"gut-microbiome-diversity","kind":"term","name":"Gut microbiome diversity and composition","route":"/terms/gut-microbiome-diversity/"}],"bottleneck":[{"id":"b-prevention-adoption","kind":"bottleneck","name":"Prevention we already have is not deployed","route":"/bottlenecks/b-prevention-adoption/"},{"id":"b-early-detection","kind":"bottleneck","name":"The hardest cancers are found late","route":"/bottlenecks/b-early-detection/"},{"id":"b-translational-valley","kind":"bottleneck","name":"The valley of death between lab and product","route":"/bottlenecks/b-translational-valley/"}],"paper":[{"id":"paper-siegel-colorectal-incidence-birth-cohort-jnci-2017","kind":"paper","name":"Colorectal cancer incidence patterns in the United States, 1974-2013","route":"/key-papers/paper-siegel-colorectal-incidence-birth-cohort-jnci-2017/"},{"id":"paper-diaz-gay-colibactin-geographic-age-mutational-processes-nature-2025","kind":"paper","name":"Geographic and age variations in mutational processes in colorectal cancer","route":"/key-papers/paper-diaz-gay-colibactin-geographic-age-mutational-processes-nature-2025/"},{"id":"paper-vuik-early-onset-colorectal-europe-gut-2019","kind":"paper","name":"Increasing incidence of colorectal cancer in young adults in Europe over the last 25 years","route":"/key-papers/paper-vuik-early-onset-colorectal-europe-gut-2019/"},{"id":"paper-hur-sugar-sweetened-beverages-early-onset-colorectal-gut-2021","kind":"paper","name":"Sugar-sweetened beverage intake in adulthood and adolescence and risk of early-onset colorectal cancer among women","route":"/key-papers/paper-hur-sugar-sweetened-beverages-early-onset-colorectal-gut-2021/"}],"idea":[{"id":"idea-crc-uk-young-patient-referral-and-diagnostic-interval","kind":"idea","name":"UK gap: shorten the route to diagnosis for patients below the screening age, where the rise in incidence is","route":"/ideas/idea-crc-uk-young-patient-referral-and-diagnostic-interval/"}]}}