Abstract PR002: Clinical, pathological, and molecular differences in early- and late-onset colorectal cancer: Results from a multicenter study
Bibliographic record
Abstract
Abstract Introduction: The incidence of colorectal cancer (CRC) in individuals under 50, referred to as early-onset colorectal cancer (EO-CRC), has risen markedly in recent decades. By 2030, EO-CRC is projected to account for 10.9% of colon and 22.9% of rectal cancers. By contrast, cases diagnosed at ≥50 years are classified as late-onset CRC (LO-CRC), corresponding to the population historically included in routine screening. Because routine screening is not offered to younger adults, EO-CRC is often detected at advanced stages, underscoring the need for tailored prevention and detection strategies. In this study, we investigated clinical, pathological, and molecular differences between EO-CRC and LO-CRC, focusing on stage distribution, tumor location, and DNA methylation profiles, and evaluated the association of age with CRC and adenoma risk. Methods: From 2018 to 2024, a total of 12,520 individuals were enrolled in a multicenter trial conducted in Spain and the United States. The cohort included 4,977 controls, 1,731 with non-advanced adenomas, 2,244 with advanced adenomas, and 3,568 with CRC. Most participants were recruited through average-risk screening colonoscopies (either first-time or surveillance after negative screening, including FIT-based programs), with additional enrollment of EO-CRC cases. For CRC patients, the distribution of tumors by stage and location was assessed. Odds ratios (ORs) were estimated to determine adenoma and CRC risk EO-CRC and LO-CRC. DNA methylation was analyzed by comparing average methylation frequency (AMF) between groups using the Mann-Whitney U test. Results: A total of 140 CRC cases were diagnosed in patients <50 years versus 3,428 in ≥50. EO-CRC patients more frequently presented with stage IV disease (22.8% vs. 12.1% in LO-CRC). Tumor distribution also differed significantly by age: EO-CRC was more often located in the distal colon (54.5% vs. 39.4% in LO-CRC) and rectum (23.6% vs. 19.2%), whereas LO-CRC was predominantly proximal (39.8% vs. 22.0% in EO-CRC). No significant association was found between age <50 and advanced adenomas (OR 0.94, p=0.54). CRC risk increased progressively with age (OR 1.24 at 50–59 to OR 3.88 at 80–89). Nevertheless, individuals <50 years had 22% higher odds of CRC compared with older groups (OR 1.22). Methylation analyses revealed significantly higher EO-CRC AMF values than age-matched controls (p=9.2e-03), with more substantial differences than those observed in LO-CRC. Conclusion: CRC risk escalates with age, yet EO-CRC is disproportionately diagnosed at advanced stages and in distal/rectal sites. Younger patients also display distinct methylation alterations, supporting a divergent tumor biology. These findings highlight the need for heightened awareness, refinement of risk stratification, and consideration of earlier screening or molecular-based surveillance in younger populations. Citation Format: NASTARAN Riahi Dehkordi, Carme D. Nolla Colomer, Francesco D. Mattia Mancuso, Kristi Kruusmaa. Clinical, pathological, and molecular differences in early- and late-onset colorectal cancer: Results from a multicenter study [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 PR002.
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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 | 0.003 | 0.004 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
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".