{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T05:10:57Z","timestamp":1788844257308,"version":"build-2803163510"},"reference-count":86,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T00:00:00Z","timestamp":1788566400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100020655","name":"European Health and Digital Executive Agency","doi-asserted-by":"crossref","award":["101104777"],"award-info":[{"award-number":["101104777"]}],"id":[{"id":"10.13039\/100020655","id-type":"DOI","asserted-by":"crossref"}]},{"award":["101104777"],"award-info":[{"award-number":["101104777"]}],"id":[{"id":"https:\/\/ror.org\/03xxypa75","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background\/Objectives: Early-onset colorectal cancer (EOCRC), diagnosed before age 50 years, is increasing in many populations and usually arises outside routine screening pathways. We synthesized clinical, demographic, familial, and genetic evidence relevant to risk-stratified early detection. Methods: Two core PubMed searches covering publications from 1 January 2010 through 1 June 2026 were supplemented by targeted PubMed searches and reference-list screening. The present review cited 82 journal publications and synthesized the findings qualitatively; no formal risk-of-bias assessment, certainty-of-evidence grading, or de novo quantitative pooling was performed. Results: EOCRC commonly involves the distal colon or rectum and presents with hematochezia, abdominal pain, altered bowel habits, or iron-deficiency anemia, with diagnostic intervals of several months. Screening colonoscopy in average-risk adults aged 45\u201349 years has a clinically relevant yield, although generally lower than in older adults, and direct evidence of reduced incidence or mortality remains limited. Risk rises with age before 50; sex and race or ethnicity provide limited, context-dependent discrimination. Family history is a consistent marker, although most cases lack documented familial aggregation. Pathogenic germline variants explain a minority, and polygenic risk scores are not established for routine practice. Conclusions: Early detection should combine timely investigation of warning signs, assessment of family history, equitable access to diagnostics, germline testing for patients with EOCRC, cascade testing, and prospective validation of population-specific models.<\/jats:p>","DOI":"10.3390\/cancers18172877","type":"journal-article","created":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T09:23:37Z","timestamp":1788773017000},"page":"2877","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Closing the Diagnostic Gap in Early-Onset Colorectal Cancer: Red-Flag Symptoms, Screening, and Inherited Risk"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8648-5541","authenticated-orcid":false,"given":"Jose M.","family":"Martin-Moreno","sequence":"first","affiliation":[{"name":"Biomedical Research Institute\u2014INCLIVA, University of Valencia, 46010 Valencia, Spain"},{"name":"Department of Preventive Medicine, Medical School, University of Valencia, 46010 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3522-5632","authenticated-orcid":false,"given":"Luis","family":"Caba\u00f1as-Alite","sequence":"additional","affiliation":[{"name":"Biomedical Research Institute\u2014INCLIVA, University of Valencia, 46010 Valencia, Spain"},{"name":"Faculty of Health Sciences, Miguel de Cervantes European University, C. del Padre Julio Chevalier, 2, 47012 Valladolid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-7063-3472","authenticated-orcid":false,"given":"Ines E.","family":"Fern\u00e1ndez-Benet","sequence":"additional","affiliation":[{"name":"Biomedical Research Institute\u2014INCLIVA, University of Valencia, 46010 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel","family":"S\u00e1nchez-Casalongue","sequence":"additional","affiliation":[{"name":"Biomedical Research Institute\u2014INCLIVA, University of Valencia, 46010 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antoni","family":"Alegre-Martinez","sequence":"additional","affiliation":[{"name":"Biomedical Research Institute\u2014INCLIVA, University of Valencia, 46010 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1775","DOI":"10.1158\/1055-9965.EPI-21-0844","article-title":"Advances in Understanding Early-Onset Colorectal Cancer","volume":"30","author":"Hayes","year":"2021","journal-title":"Cancer Epidemiol. 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