Continued support of the Great Lakes New England (GLNE) Clinical Validation Center (CVC) of the Early Detection Research Network (EDRN) via the U01 mechanism is requested. The GLNE CVC is a highly collaborative, multi-institutional consortium designed to develop, implement and analyze trials for the validation of biomarkers for the early detection of colorectal adenocarcinoma and other Gl malignancies. Over the last 5 years, the GLNE has developed a high quality biosample repository of samples collected from human subjects with colorectal and lower esophageal neoplasias and controls. The GLNE has preliminary characterization of 16 biomarkers for the early detection of colorectal adenocarcinoma and 3 biomarkers for the detection of progression of lower esophageal metaplasia to dysplasia and carcinoma. The GLNE has collaborated with 5 biomarker developmental laboratories, 4 biomarker reference laboratories, the EDRN DMCC, and 5 industrial partners publishing 23 manuscripts including 15 manuscripts collaborating with other EDRN centers. In the next grant period, the GLNE-CVC proposes to 1. To determine the performance of vimentin methylation, galectin-3 ligand, the Exact stool DNA panel, and fecal immunochemical test (FIT) for the early detection of colorectal neoplasia using colonoscopy as the gold standard;2. To determine if vimentin methylation, galectin-3 ligand, Exact sciences stool DNA panel, or any future individual biomarker alone performs better than fecal immunochemical testing for the detection of colorectal adenocarcinoma and high grade dysplasia;3. To determine the screening performance of vimentin methylation in stool, galectin-3 ligand, Exact sciences stool DNA panel, or any future individual biomarker or FIT together for detection of colorectal adenocarcinoma and high grade dysplasia;and 4. To establish an archive of appropriately preserved stool, serum, plasma, urine, and DNA human biospecimens to be used by EDRN investigators for future validation and biomarker discovery research.
These aims will be addressed by a multi-institutional consortium of university and community Gl practices recruiting human subjects undergoing screening colonoscopy under a PRoBE compliant protocol. The protocol requires the implementation of detailed standard operating procedures for biosample collection and management and associates these biosamples with EDRN compliant data elements. The data will be managed and analyzed by the EDRN data management and coordinating center. Biosamples will be collected for future biomarker colorectal cancer early detection validation trials and to support EDRN biomarker discovery and prevalidation.

Public Health Relevance

Cancer mortality is caused by dissemination from the primary site. Through development and validation of biomarkers that signal the presence of risk or a cancer, individuals at high risk or with early stage cancers are identified. Early cancers can be removed at a curable stage, reducing cancer mortality while individuals at high risk can be monitored closely and interventions to delay or reverse the cancer process provided.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Project--Cooperative Agreements (U01)
Project #
Application #
Study Section
Special Emphasis Panel (ZCA1)
Program Officer
Rinaudo, Jo Ann S
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Michigan Ann Arbor
Internal Medicine/Medicine
Schools of Medicine
Ann Arbor
United States
Zip Code
Baxter, Nielson T; Ruffin 4th, Mack T; Rogers, Mary A M et al. (2016) Microbiota-based model improves the sensitivity of fecal immunochemical test for detecting colonic lesions. Genome Med 8:37
Baxter, Nielson T; Koumpouras, Charles C; Rogers, Mary A M et al. (2016) DNA from fecal immunochemical test can replace stool for detection of colonic lesions using a microbiota-based model. Microbiome 4:59
Yu, Ming; O'Leary, Rachele M; Kaz, Andrew M et al. (2015) Methylated B3GAT2 and ZNF793 Are Potential Detection Biomarkers for Barrett's Esophagus. Cancer Epidemiol Biomarkers Prev 24:1890-7
Zackular, Joseph P; Rogers, Mary A M; Ruffin 4th, Mack T et al. (2014) The human gut microbiome as a screening tool for colorectal cancer. Cancer Prev Res (Phila) 7:1112-21
Rho, Jung-hyun; Mead, Judson R; Wright, W Shea et al. (2014) Discovery of sialyl Lewis A and Lewis X modified protein cancer biomarkers using high density antibody arrays. J Proteomics 96:291-9
Brenner, Dean E; Hawk, Ernest (2013) Trials and tribulations of interrogating biomarkers to define efficacy of cancer risk reductive interventions. Cancer Prev Res (Phila) 6:71-3
Baron, John A (2012) Screening for cancer with molecular markers: progress comes with potential problems. Nat Rev Cancer 12:368-71
Yurgelun, Matthew B; Goel, Ajay; Hornick, Jason L et al. (2012) Microsatellite instability and DNA mismatch repair protein deficiency in Lynch syndrome colorectal polyps. Cancer Prev Res (Phila) 5:574-82
Yue, Tingting; Maupin, Kevin A; Fallon, Brian et al. (2011) Enhanced discrimination of malignant from benign pancreatic disease by measuring the CA 19-9 antigen on specific protein carriers. PLoS One 6:e29180
Ruffin, Mack T; Normolle, Daniel P; Evelegh, Michael J et al. (2010) Rectal mucosal quantitative galactose oxidase-Schiff reaction as an early detection biomarker for colorectal cancer: comparison to fecal occult stool blood test. Cancer Biomark 8:109-12

Showing the most recent 10 out of 28 publications