Clinical Rather Than Genetic Factors Drive Prognosis in Early- Onset Colorectal Cancer: A Retrospective Cohort Study

Clinical Rather Than Genetic Factors Drive Prognosis in Early- Onset Colorectal Cancer: A Retrospective Cohort Study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Clinical Rather Than Genetic Factors Drive Prognosis in Early- Onset Colorectal Cancer: A Retrospective Cohort Study Kien Trung Le, Huy Duc Tran, Minh Duc Do, Thinh Huu Nguyen, Tin Trung Nguyen, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9338468/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 10 You are reading this latest preprint version Abstract Background Early-onset colorectal cancer (EOCRC) is increasing globally and exhibits both aggressive clinicopathological features and distinct molecular characteristics. However, the relative contribution of clinical and genetic factors to prognosis remains unclear, particularly in underrepresented populations. Methods A retrospective cohort study was conducted on 100 colorectal cancer (CRC) patients under 50 years of age, diagnosed and treated between January 2016 and December 2020, with follow-up up to 60 months or until death. Patients were stratified by patient characteristics, oncological features, and genetic mutation status to perform overall survival (OS) analysis. Results The mean OS was 49.8 months (95% CI: 46.4–53.2), with an estimated 5-year OS rate of 65.2%. The mean disease-free survival (DFS) was 50.1 months (95% CI: 46.2–53.9). In univariate analysis, factors significantly associated with OS included serum CEA level at diagnosis (p = 0.001), histological grade (p = 0.006), mode of surgery (emergency vs. elective) (p = 0.003), curative resection status (p < 0.001), disease stage (p < 0.001), mutations in the POL–MMR DNA repair gene group (p = 0.035), high mutation accumulation (p = 0.020), PIK3CA mutation (p = 0.036), and co-mutation of RAS/RAF and MMR genes (p = 0.011). However, when adjusted for disease stage, only patient and oncological factors remained associated with OS, including elevated CEA (HR = 2.33, 95% CI: 1.2–4.7, p = 0.018), poorly differentiated tumors (HR = 2.57, 95% CI: 1.2–5.7, p = 0.021), emergency surgery (HR = 3.50, 95% CI: 1.5–7.9, p = 0.003), and curative treatment (HR = 0.10, 95% CI: 0.05–0.2, p < 0.001). Conclusion In EOCRC, clinical and treatment-related factors outweigh genetic alterations in determining prognosis after adjustment for disease stage. These findings highlight the importance of optimizing clinical management strategies, while the prognostic role of genetic factors appears to be limited. early-onset colorectal cancer long-term outcomes gene mutations Vietnam Full Text Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Reviews received at journal 12 May, 2026 Reviews received at journal 11 May, 2026 Reviewers agreed at journal 04 May, 2026 Reviewers agreed at journal 29 Apr, 2026 Reviewers agreed at journal 29 Apr, 2026 Reviewers invited by journal 29 Apr, 2026 Editor invited by journal 08 Apr, 2026 Editor assigned by journal 07 Apr, 2026 Submission checks completed at journal 07 Apr, 2026 First submitted to journal 06 Apr, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-9338468","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":635751175,"identity":"a8a636c6-e680-4c67-a8e2-12eb6cd073d0","order_by":0,"name":"Kien Trung Le","email":"","orcid":"","institution":"Univercity Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Kien","middleName":"Trung","lastName":"Le","suffix":""},{"id":635751176,"identity":"b46846f3-2d62-459c-881e-0699074e3c7f","order_by":1,"name":"Huy Duc 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02:38:55","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-9338468/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9338468/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":108806166,"identity":"3fc29a65-9b81-47da-96bb-f7201335f6ec","added_by":"auto","created_at":"2026-05-08 15:27:52","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":575689,"visible":true,"origin":"","legend":"","description":"","filename":"EOCRCBMCcancerplain.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9338468/v1_covered_3f88c488-c25e-419a-808a-f1371c27451c.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Clinical Rather Than Genetic Factors Drive Prognosis in Early- Onset Colorectal Cancer: A Retrospective Cohort 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Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"early-onset colorectal cancer, long-term outcomes, gene mutations, Vietnam","lastPublishedDoi":"10.21203/rs.3.rs-9338468/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9338468/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eEarly-onset colorectal cancer (EOCRC) is increasing globally and exhibits both aggressive clinicopathological features and distinct molecular characteristics. However, the relative contribution of clinical and genetic factors to prognosis remains unclear, particularly in underrepresented populations.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eA retrospective cohort study was conducted on 100 colorectal cancer (CRC) patients under 50 years of age, diagnosed and treated between January 2016 and December 2020, with follow-up up to 60 months or until death. Patients were stratified by patient characteristics, oncological features, and genetic mutation status to perform overall survival (OS) analysis.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eThe mean OS was 49.8 months (95% CI: 46.4\u0026ndash;53.2), with an estimated 5-year OS rate of 65.2%. The mean disease-free survival (DFS) was 50.1 months (95% CI: 46.2\u0026ndash;53.9). In univariate analysis, factors significantly associated with OS included serum CEA level at diagnosis (p\u0026thinsp;=\u0026thinsp;0.001), histological grade (p\u0026thinsp;=\u0026thinsp;0.006), mode of surgery (emergency vs. elective) (p\u0026thinsp;=\u0026thinsp;0.003), curative resection status (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), disease stage (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), mutations in the POL\u0026ndash;MMR DNA repair gene group (p\u0026thinsp;=\u0026thinsp;0.035), high mutation accumulation (p\u0026thinsp;=\u0026thinsp;0.020), \u003cem\u003ePIK3CA\u003c/em\u003e mutation (p\u0026thinsp;=\u0026thinsp;0.036), and co-mutation of RAS/RAF and MMR genes (p\u0026thinsp;=\u0026thinsp;0.011). However, when adjusted for disease stage, only patient and oncological factors remained associated with OS, including elevated CEA (HR\u0026thinsp;=\u0026thinsp;2.33, 95% CI: 1.2\u0026ndash;4.7, p\u0026thinsp;=\u0026thinsp;0.018), poorly differentiated tumors (HR\u0026thinsp;=\u0026thinsp;2.57, 95% CI: 1.2\u0026ndash;5.7, p\u0026thinsp;=\u0026thinsp;0.021), emergency surgery (HR\u0026thinsp;=\u0026thinsp;3.50, 95% CI: 1.5\u0026ndash;7.9, p\u0026thinsp;=\u0026thinsp;0.003), and curative treatment (HR\u0026thinsp;=\u0026thinsp;0.10, 95% CI: 0.05\u0026ndash;0.2, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eIn EOCRC, clinical and treatment-related factors outweigh genetic alterations in determining prognosis after adjustment for disease stage. These findings highlight the importance of optimizing clinical management strategies, while the prognostic role of genetic factors appears to be limited.\u003c/p\u003e","manuscriptTitle":"Clinical Rather Than Genetic Factors Drive Prognosis in Early- Onset Colorectal Cancer: A Retrospective Cohort Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-05-08 00:06:39","doi":"10.21203/rs.3.rs-9338468/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorInvitedReview","content":"","date":"2026-05-12T20:50:25+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-05-11T08:21:47+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"114814005860652872196465939674262740612","date":"2026-05-04T11:26:22+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"83975510307333052394691162269967907699","date":"2026-04-29T17:52:54+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"146338117097927828558189512745092904517","date":"2026-04-29T10:20:27+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-04-29T09:28:53+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2026-04-08T17:15:42+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-04-07T23:59:20+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-04-07T23:59:16+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Cancer","date":"2026-04-07T02:31:23+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-cancer","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bcan","sideBox":"Learn more about [BMC Cancer](http://bmccancer.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bcan/default.aspx","title":"BMC Cancer","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"382b6dd8-e40d-4b27-ad32-58d176c255a0","owner":[],"postedDate":"May 8th, 2026","published":true,"recentEditorialEvents":[{"type":"editorInvitedReview","content":"","date":"2026-05-12T20:50:25+00:00","index":68,"fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-05-11T08:21:47+00:00","index":66,"fulltext":""},{"type":"reviewerAgreed","content":"114814005860652872196465939674262740612","date":"2026-05-04T11:26:22+00:00","index":45,"fulltext":""},{"type":"reviewerAgreed","content":"83975510307333052394691162269967907699","date":"2026-04-29T17:52:54+00:00","index":43,"fulltext":""},{"type":"reviewerAgreed","content":"146338117097927828558189512745092904517","date":"2026-04-29T10:20:27+00:00","index":42,"fulltext":""},{"type":"reviewersInvited","content":"30","date":"2026-04-29T09:28:53+00:00","index":"","fulltext":""}],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-05-08T00:06:39+00:00","versionOfRecord":[],"versionCreatedAt":"2026-05-08 00:06:39","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9338468","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9338468","identity":"rs-9338468","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}