Abstract B003: Risk Factors, Clinical and Molecular Characteristics of de novo Metastatic Early Onset Colorectal Cancer
Notice bibliographique
Résumé
Abstract Background: Early onset colorectal cancer (EO CRC) is rising worldwide. Epidemiologic studies have shown diets high in sugar are associated with EO CRC when compared to healthy controls. Preclinical work reported that high fructose diets increase colorectal tumor size; however, an association with clinical outcomes has not yet been established. Investigating risk factors, clinical and molecular characteristics of de novo metastatic EO CRC is an unmet need. Methods: All eligible EO CRC patients were enrolled in MSK’s Center for Young Onset Colorectal and Gastrointestinal Cancer and completed a risk factor questionnaire (MSK-approved IRB #20-315). We analyzed questionnaire responses and compared risk factors between patients with de novo metastatic disease vs localized disease using Wilcoxon rank sum test or Fisher’s exact test. Overall survival was estimated using Kaplan-Meier methods. Tumors (n=206) were sequenced using MSK-IMPACT (MSK-approved IRB #12-245) and underwent genomic analyses. A subset of samples (n=37) were recaptured using Whole Exome Sequencing (WES) and processed using the Tempo pipeline at MSKCC. Somatic mutations from WES samples were fitted to 11 predefined CRC-relevant COSMIC SBS mutational signatures using tempoSig. Stool samples (n=87) were also collected for 16S sequencing and aggregated to genus level for analysis. Alpha diversity (Shannon index) was compared using Wilcoxon rank-sum test. Beta diversity was assessed using Aitchison distance and tested using PERMANOVA. Results: 303 patients completed the questionnaire (median age at diagnosis 42; 51% Female; 88% left-sided tumors). 112 had de novo stage IV disease and 191 had stage I-III disease. Patients with de novo metastatic disease were younger, 40.9 [95%CI: 36.8 - 44.8] vs. 43.0 [95%CI: 38.4 - 46.4] (P-value0.037). High sugar diets were significantly associated with de novo metastatic disease, with 30 (45%) vs. 37 (29%) (P-value, 0.004) patients reporting daily consumption of high sugar foods. 3-year OS in the metastatic population was 72% [95%CI: 62% - 84%] vs. 99% [95%CI: 98% - 100%]. Within the metastatic group, no association was observed between daily high sugar consumption and non-daily consumption in terms of PFS or OS. 3-year OS in the daily high sugar group was 79 % [95%CI: 62%-100%] vs 74% [95%CI: 57%-95%]. Genomic analyses revealed no significant differences in tumor mutational burden, fraction genome altered, frequency of oncogenic or signaling pathway alterations in de novo metastatic vs. non-metastatic patients. Similarly, in metastatic patients who reported daily consumption of high sugar foods, there was no distinct genomic profiles. Microbiome analyses also showed no differences in alpha or beta diversity. Conclusions: In a single center study, in EO CRC patients, high sugar diets may be associated with de novo metastatic disease. There were no significant differences at the genome or microbiome level. Future studies are warranted to interrogate the components of high sugar diets and their impact on tumorigenesis. Citation Format: Emma Schatoff, Ramzi Homsi, Joanne F. Chou, Marinela Capanu, Henry Walch, Lerie Palmaira, Jill Weiss, Jordana Kaller, Callahan Wilde, Walid Chatila, Robin Mendelsohn, Andrea Cercek. Risk Factors, Clinical and Molecular Characteristics of de novo Metastatic Early Onset Colorectal Cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: The Rise in Early-Onset Cancers—Knowledge Gaps and Research Opportunities; 2025 Dec 10-13; Montreal, QC, Canada. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(23_Suppl):Abstract nr B003.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,002 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,001 | 0,001 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,012 | 0,001 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».