{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T20:41:21Z","timestamp":1788813681947,"version":"build-2803163510"},"reference-count":77,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T00:00:00Z","timestamp":1788393600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"European Union via the European Health and Digital Executive Agency","award":["101104777"],"award-info":[{"award-number":["101104777"]}]},{"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 countries, but its causes remain uncertain. Evidence on potentially modifiable determinants is heterogeneous and vulnerable to retrospective assessment and residual confounding. We synthesized metabolic, behavioral, dietary, medication-related, clinical, and socioeconomic factors, emphasizing consistency and life-course relevance. 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 75 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: Evidence was most consistent for excess adiposity and cardiometabolic dysfunction, with earlier and persistent exposure and cardiometabolic clustering potentially more relevant. Inflammatory bowel disease emerged as a clinically distinct high-risk condition. Sedentary behavior, smoking, and higher alcohol consumption showed recurrent but heterogeneous associations. Dietary findings varied by pattern and component: sugar-sweetened beverages and lower-quality dietary patterns showed positive associations, whereas fiber- and plant-rich diets, calcium, folate, and vitamin D showed possible inverse associations. Dietary evidence was largely retrospective and does not establish causality. Evidence for aspirin and antibiotics was limited and vulnerable to confounding, precluding causal inference. Most patterns resembled later-onset CRC. Conclusions: Current evidence does not support a wholly distinct set of environmental determinants for EOCRC. Earlier exposure, longer duration, and cumulative interaction of CRC risk factors are plausible explanations but remain incompletely tested. Evidence supports life-course primary prevention, but no single factor should determine screening eligibility in isolation. Prospective studies with repeated exposure measurement are needed.<\/jats:p>","DOI":"10.3390\/cancers18172852","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T09:20:43Z","timestamp":1788427243000},"page":"2852","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Understanding the Rising Incidence of Early-Onset Colorectal Cancer: Life-Course Determinants and Opportunities for Primary Prevention"],"prefix":"10.3390","volume":"18","author":[{"given":"Antoni","family":"Alegre-Martinez","sequence":"first","affiliation":[{"name":"Biomedical Research Institute\u2014INCLIVA, 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"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8648-5541","authenticated-orcid":false,"given":"Jose M.","family":"Martin-Moreno","sequence":"additional","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"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,3]]},"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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