Abstract 7017: Increased epigenetic age acceleration in young adult and early onset colorectal cancer patients post-treatment: A ColoCare Pilot Study

Abstract Introduction: Advanced biological age relative to chronological age has been observed in individuals with colorectal cancer (CRC), and there is growing evidence that cancer treatments can further accelerate biological aging. However, the influence of age at diagnosis on these relationships has yet to be examined in detail. This pilot study used data from the ColoCare Study to explore pre- and post-treatment differences in age acceleration by chronological age at CRC diagnosis. Methods: The ColoCare Study is a prospective cohort study of newly-diagnosed CRC patients enrolled across seven U.S. and European sites. Participants in this pilot study were from the ColoCare site in Tampa, Florida who had available pre-treatment blood DNA. Young adult (YA, aged 18-39) and early onset (EO, aged 40-49) participants were matched with average onset (AO, aged 50-64) and late onset (LO, aged >64) participants on stage, sex, race and microsatellite instability status. Genome-wide DNA methylation profiles were assayed on buffy coat DNA using MethylationEPIC v2 BeadChips. PhenoAgeAccel and GrimAgeAccel were calculated on all samples to quantify the difference between DNA methylation-predicted biological age and chronological age (i.e., age acceleration). Linear regression models were used to estimate the associations of age at diagnosis and treatment with PhenoAgeAccel and GrimAgeAccel, adjusted for sex, race, and site (rectal, colon). Results: The sample (n=60) included n=19 YA, n=15 EO, n=11 AO, and n=15 LO participants with pre-treatment blood DNA. Over half (n=15 YA/EO, n=20 AO/LO) had a paired post-treatment blood sample available. Half of participants were female and had colon tumors, and 76% were diagnosed with stage I-III disease. Pre-treatment, PhenoAgeAccel and GrimAgeAccel were similar across age groups (P > 0.05). In the subset of participants with pre- and post-treatment samples, age acceleration appeared to increase post-treatment (pre- and post-treatment differences, PhenoAgeAccel: 1.44, SD: 5.55, P= 0.13; GrimAgeAccel: 0.92, SD: 2.80, P= 0.06). Increases were largest among YA/EO participants. In adjusted models, the predicted differences in pre-to post-treatment PhenoAgeAccel were 2.89 (95% CI: -0.13, 5.90) in YA/EO and 0.36 (95% CI: -2.25, 2.96) in AO/LO (P-difference= 0.20). The predicted differences in GrimAgeAccel were 1.75 (95% CI: 0.25, 3.25) in YA/EO and 0.30 (95% CI: -1.00, 1.60) in AO/LO (P-difference= 0.15). Conclusions: In this pilot study of CRC patients, pre-treatment age acceleration did not vary by age at diagnosis. Post-treatment, patients diagnosed at age 49 or younger had larger increases in age acceleration than patients diagnosed at age 50 or older. These findings warrant further investigation in larger samples and to determine if increases in post-treatment age acceleration as associated with patient outcomes and treatment response. Citation Format: Erin M. Siegel, Jacob K. Kresovich, Amanda M. Bloomer, Anders Berglund, Esther Jean-Baptiste, Gillian Trujillo, Rachel Carmella, Julaxis Love, Seth Felder, Jennifer Ose, Biljana Gigic, Christopher I. Li, Jane C. Figueiredo, Adetunji T. Toriola, Cornelia M. Ulrich, David Shibata, Laura B. Oswald. Increased epigenetic age acceleration in young adult and early onset colorectal cancer patients post-treatment: A ColoCare Pilot Study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7017.