W45 – Validation of candidate markers found in EDRN Proteomic Colon Cancer Study (W20)
This site provides study documentation for the W45 Core Study. Datasets for this study are contained within the existing WHI datasets, located on the Data site (a completed Data Distribution Agreement is required; see details on the Data site).
Investigator Names and Contact Information
Core study approved by WHI Steering Committee
Introduction/Intent
From core study W20 - EDRN Proteomic Colon Cancer Study, circulating proteins were found to be significantly (p < 0.05) up-regulated in the cases relative to controls. Of interest is a set of proteins with known association with cancer including MAPRE1, SPARC, SERPINA1, IGFBP2, KNG1, LRG1, SLURP1, which are plausible candidates for early detection of colon cancer. In particular, MAPRE1 is known to be an interacting protein with the APC protein whose gene is mutated early during colon cancer development. It is noteworthy that MAPRE1 is known to bind to APC at the site that is mutated in colon cancer, raising the possibility that increased levels of MAPRE1 in blood may provide an early indication of colon cancer development. Additionally, serological reactivity against a set of tumor antigens was observed among cases compared to controls. In particular, significant reactivity was observed against a set of four separate arrayed protein fractions, which all turned out to consist of different members of the heterogeneous nuclear ribonucleoprotein family.
These promising findings from the two parallel studies require confirmation. An aliquot from an independent set of 100 cases occurring within one year following the baseline blood draw and 100 matched controls is requested to validate findings from the discovery study. Circulating candidate markers will be validated using immunological methods. Reactivity to tumor antigens will be evaluated using antigen microarrays.
Circulating candidate markers will be validated using immunological methods, primarily ELISA and SPR Resonance). Reactivity to tumor antigens will be evaluated using antigen microarrays that will be constructed to include the candidate antigens.