Abstract 1890: Proteomic analysis of colorectal cancer risk across two prospective cohorts

Abstract High-throughput proteomic profiling in prospective cohorts has the potential to uncover biomarkers of cancer risk and biology of cancer development. We investigated prospective associations of up-to 7, 335 aptamers with overall and site-specific colorectal cancer in a case-cohort study within the European Prospective Investigation into Cancer and Nutrition (EPIC) and then evaluated associations in the Atherosclerosis Risk in Communities (ARIC) study. Hazard ratios and 95% confidence intervals were estimated using Prentice weighted Cox-proportional hazard models (stratified by recruitment center, sex, and 5 year age group and adjusted for fasting status, day of blood draw, body mass index, smoking status, daily alcohol consumption, physical activity level, and highest level of education) in 977 incident colorectal (colon, 658; rectum, 319) cancer cases and 5, 057 non-cases under a case-cohort design. The identified associations were then evaluated in ARIC in a cohort design including 271 colorectal (colon, 235; rectum, 36) cancers in 9, 495 individuals using multivariate Cox-proportional hazard models. Overall, 37 aptamers were associated (false discovery rate[FDR] p-value < 0.05) with colorectal cancer in EPIC; data on 27 of these were available in ARIC, 7 of which had consistent directions of association in both studies and met a nominal p-value (0.05) threshold in ARIC (positive associations: ACAA1, ASL, GDF15, IQCF1, TFF3; inverse associations: CLEC3B, COMP). Associations did not change after 5-year follow-up exclusion. In site-specific analyses in EPIC, 66 and 6 aptamers were specifically associated with colon and rectal cancer, respectively at FDR<0.05. Four of these aptamers were nominally (P<0.05) associated with colon cancer in ARIC (inverse association: CLEC3B; positive association: ACAA1, GDF15, TFF3) while a further 29 showed associations directionally consistent with those in EPIC. These large-scale proteomic analyses identified a set of proteins associated with colorectal cancer risk across two independent cohorts. These proteins reflect pathways involved in cell migration and adhesion, colorectal mucosal integrity and growth and differentiation, among others, and may represent novel biomarkers of colorectal cancer risk. Citation Format: Matthew A. Lee, Vivian Viallon, David C. Muller, Ziqiao Wang, Paula Jakszyn, Pietro Ferrari, Giovanna Masala, Domenico Pali, Salvatore Panico, Carlotta Sacerdote, Karl Smith-Byrne, Ruth C. Travis, 8 Rosario Tumino, P. Martijn Kolijn, Roel Vermeulen, Monique Verschuren, Nicholas Wareham, Elizabeth A. Platz, Nilanjan Chatterjee, Elio Riboli, Marc J. Gunter. Proteomic analysis of colorectal cancer risk across two prospective cohorts [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 1890.