Evaluation of stool-based markers for the early detection of colorectal cancers and adenomas.
Primary Investigator: Kim Turgeon MD
Missy Tuck, M.S., Clinical Research Project Manager
Phone: (734) 763-1141
Fax: (734) 764-2566
In recognition of the fact that novel potential biomarkers are continually being identified and will need to be validated in a rapid, efficient and scientifically rigorous manner, the NCI has made an enormous commitment to the development of a network that will facilitate biomarker development and validation in multiple organ sites. As part of the National Cancer Institute-funded Early Detection Research Network (EDRN), the Great Lakes-New England Clinical Epidemiological Center (GLNE CEC) proposes a research study that validates potential molecular markers (“biomarkers”) for the detection of precancerous and cancerous conditions and cancer risk assessment. Although examples of such biomarkers are currently in clinical use (i.e. CEA, CA-125), there are limitations to all of them. Our consortium focuses on gastrointestinal neoplasia.
The goals of this phase of the proposed research are as follows:
1. Preliminary exploration of sensitivity and specificity relative to adenocarcinomas, adenomas and normal tissue of stool-based biomarkers to be considered for a future panel for the early detection of colonic neoplasia.
2. Characterization of the utility of individual markers and prototype panels under a number of assumptions concerning prevalence and cost of misclassification.
3. Preliminary exploration of sensitivity and specificity relative to adenocarcinomas, adenomas and normal tissue of serum-based or urine-based biomarkers to be considered for a future panel for the early detection of colonic neoplasia.
4. Construction of a panel of markers from Objective 1 to classify:
-Participants with normal colons versus participants with adenomas or cancers
-Participants with normal colons or adenomas versus participants with cancers.
-Participants with normal colons versus participants with adenomas versus participants with cancers.
5. Comparison of the markers and panels to the established current standard, FOBT.
6. Assess the usefulness of two different stool collection tools for detection of stool based
7. Development of a bank of stool samples linked to serum, tissue, urine and clinical data from patients with colorectal cancer, adenomas and normal controls for validation of stool-based markers that may be developed in the future.
To meet our goals we propose to collect stool, serum, plasma and urine samples from 600 patients (200 colorectal cancer, 200 adenomas and 200 controls). The stool samples will be assayed for 5 stool based biomarkers. EDRN Common Data Elements (CDEs) will be completed by the recruiting sites and provided for the laboratories developing the assay. Each biomarker will be analyzed individually and considered as a potential panel marker to be used for future large-scale screening longitudinal trials.
Based upon the outcomes of a subset of these biomarkers, samples will be then sent to the UCLA Biomarker Validation Lab (BVL) for assay validation and preparation for a biomarker panel validation project. This validation project will be the subject of a subsequent protocol.