Abstract A025: Accelerated aging as a predictor for early onset colorectal cancer

Abstract Background: The median age of early onset colorectal cancer (EOCRC) is 44 years old. Given that screening begins at age 45, there is a substantial screening gap. Identifying individuals at risk of EOCRC and offering early screening is an optimal solution, but risk factors remain poorly defined. A few studies have demonstrated an association between accelerated aging (an individual’s biological age exceeding chronological age) and increased EOCRC risk, as well as risk of preneoplastic polyps. However, biological age metrics are not standardized and require resource intensive epigenetic analyses. PhenoAge is an accessible biological age metric based on peripheral blood sampling and routine laboratory markers. We evaluate whether PhenoAge and colorectal adenomas (CRAs) correlate in persons under age 50 undergoing colonoscopy for benign indications. Such an approach has the potential to identify patients at risk for EOCRC while minimizing healthcare burden associated with early CRC screening. Methods: This is a prospective study with IRB approval of average-risk patients undergoing screening colonoscopy at a single institution between February 2025 and August 2025. Participants provided informed consent for peripheral blood draws at the time of colonoscopy. Biological age was determined using the PhenoAge calculation based on bloodwork results. Polyp detection during colonoscopy was conducted according to standard practice. Polyp characteristics, pathologic findings, medical history, and demographics were obtained from the electronic medical record. Relationships between polyp presence and patient demographics and medical history were compared using chi-square test for categorical values and Wilcoxon signed-rank test for continuous values. Results: A total of 41 patients were included in this cohort. Median age was 47 years old and 25 (61%) were female. Among these 41, 14 (34%) were found to have at least 1 adenoma on colonoscopy. There were no significant differences in sex, race, ethnicity, country of birth, body mass index, metabolic syndrome, or indication between those with or without CRA. The median age acceleration among patients with CRA was –4. 7 years and –3. 6 among those without CRA (p = 0. 294). Those with CRA demonstrated a greater proportion of current smokers (28. 6%) compared to those without CRA (3. 7%) (p = 0. 095). 36% of patients with CRA had hypertension compared to 22% of those without CRA (p= 0. 463). Conclusions: Accelerated aging as a marker for early onset cancer screening has not been extensively studied. Existing literature demonstrates an association between accelerated aging and increased EOCRC risk. This is a pilot study with a small sample size that provides foundational data to support future studies in using accelerated aging as a predictor for polyps in average-risk persons under age 50. As the healthcare burden of colorectal cancer screening grows with the increasing incidence of EOCRC, less invasive methods of identifying patients at risk for EOCRC such as using blood-based screening are urgently needed. Citation Format: Karen Zhang, Catherine Blandon, Shria Kumar. Accelerated aging as a predictor for 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 (23Suppl): Abstract nr A025.