AS505 – Validation of colorectal cancer early detection markers

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Investigator Names and Contact Information

Paul Lampe [ plampe@fhcrc.org ]

Introduction/Intent

Colorectal cancer (CRC) is one of the most common cancers in the United States and the second ranked cause of cancer related death among men and women combined. Early detection of CRC clearly saves lives. We have used our high density antibody array to discover potential early detection biomarkers of colorectal cancer in samples collected during the Cardiovascular Health Study (CHS) for people diagnosed up to 2 years from blood draw.  We determined a 4-marker panel that had an AUC=0.84.  We then tested these markers in control, advanced adenoma and stages I-IV colon cancer diagnostic samples supplied by the Early Detection Research Network (EDRN) and found AUCs for the combined panel ranged from 0.92-0.96 for the different combinations.  In particular, comparing controls to advanced adenoma and stage I and II cancers, people thought most to benefit from early intervention, yielded an AUC=0.93 (84% sensitivity at 90% specificity).  We then tested these markers in adenoma samples collected in a colonoscopy study conducted at the University of Minnesota and confirmed the upregulation and identification of these markers. We need to perform a blinded validation study with samples appropriate for early detection (i.e., pre-diagnostic). We propose to validate these markers in a case-control design study with samples collected by the WHI using women that had a CRC diagnosis within 2 years of blood draw (controls would be matched on age, BMI, race, smoking status). Specifically, we request 150 µl of EDTA-plasma samples from all CRC cases in the WHI Observational Study that were diagnosed with colorectal cancer within 2 years a blood draw (~288 centrally adjudicated) and two matched controls per case (~576).

Specific Aims

Specific Aim 1. Test the plasma level of 4 markers in 288 women who develop colorectal cancer within 2 years of blood draw compared to twice the number of matched controls.

Specific Aim 2.  Determine whether this 4 marker panel and the potential addition of cancer specific glycosylation changes in these markers performs well enough to warrant further investigation in larger sets and those further from diagnosis.