Abstract B003: Risk Factors, Clinical and Molecular Characteristics of de novo Metastatic Early Onset Colorectal Cancer
Bibliographic record
Abstract
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.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.012 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".