Abstract Longitudinal blood collections from cohort studies provide the means to search for proteins associated with disease processes prior to diagnosis. We have investigated pre-diagnostic plasma samples to determine quantitative differences in plasma protein between subjects subsequently diagnosed with colorectal cancer (CRC) and matched controls that remain cancer free during an 18 month period of active follow-up. In-depth quantitative proteomic profiling was performed on 90 pre-diagnostic plasma samples. Experiments compared nine pools each consisting of plasma aliquots from 10 CRC subjects diagnosed within 18 months after blood draw and 10 matched controls. MAPRE1 was confirmed in a set of 58 pairs of plasma from newly diagnosed CRC cases and controls using enzyme linked immunosorbent assay (ELISA). MAPRE1 was further tested by ELISA in a second independent set of 100 pre-diagnostic CRC plasma samples diagnosed within 18 months after blood draw and 100 matched controls. Proteomic analysis of pre-diagnostic plasma samples collected prior to diagnosis of CRC yielded a set of proteins with elevated concentrations (p <0.05) in cases compared to control that included MAPRE1 which is a binding partner for APC. MAPRE1 and carcinoembryonic antigen (CEA) were assayed by ELISA in newly diagnosed CRC samples, yielding equally significant elevation (p <0.05) among cases relative to controls for each protein with areas under the curve (AUCs) of 0.778 and 0.782, respectively. Further testing in an independent set of pre-diagnostic samples confirmed predictive value of MAPRE1 by receiver operator characteristic (ROC) achieving an AUC of 0.675 within 7 months of diagnosis. This is the first reported evidence of elevated circulating levels of MAPRE1 in colorectal cancer patient plasma. Plasma levels increased with development of CRC. Because of MAPRE1's interaction with adenomatous polyposis coli protein (APC), a known target of mutation in a majority of CRC, increased circulating levels of MAPRE1 may be an early indicator of CRC development. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5102. doi:10.1158/1538-7445.AM2011-5102