Abbreviated Name

EDRN/WHI COLON

Lead Investigator

Hanash, Samir — The University of Texas MD Anderson Cancer Center

Coordinating Investigator

Feng, Ziding — Fred Hutchinson Cancer Center

Involved Investigators

• Feng, Ziding — Fred Hutchinson Cancer Center
• Semmes, John — Eastern Virginia Medical School
• Chinnaiyan, Arul M. — University of Michigan
• Chan, Daniel — Johns Hopkins Medical Institutions
• Hanash, Samir — The University of Texas MD Anderson Cancer Center
• Srivastava, Sudhir — National Cancer Institute
• Bigbee, William L. — University of Pittsburgh Cancer Institute

Abstact

A pioneering collective discovery project using colon cancer pre-diagnostic plasma and controls is proposed as a joint Early Detection Research Network-Women’s Health Initiative (EDRN-WHI) study. One half ml of plasma from 100 colon cancer cases and an equal number of pair matched controls from the Observational Study (OS) will be aliquotted and made available by WHI for analysis using complementary proteomic platforms to assess the potential of proteomics technologies to generate leads concerning early detection markers or risk prediction markers for colon cancer, and to compare and contrast findings between proteomic platforms. Colon cancer cases that occur within a span of 18 months following year-3 OS blood draw will be selected. The platforms considered will include the commonly used ‘peptide shotgun’ approach, a comprehensive, quantitative intact plasma protein approach, tumor antigen/autoantibody approaches, a peptide capture mass spectrometry approach, and glycoprotein enrichment approaches. In phase 1, which is expected to last six months, participating investigators will analyze their own data. However by the end of phase one investigators are expected to have deposited their data in a central database for integrated analysis. The data will be publicly accessible following publication. The NCI Early Detection Research Network is expected to contribute most of the funding needed for this project.

Aims

Specific Aims are identified by each assay laboratory.

Analytic Method

The primary analysis for this study is to identify proteins/peptides that have potential as colon cancer early detection or risk prediction markers for subsequent validation. The secondary aim is to see if some proteins/peptides are complementary in their early detection abilities so their combinations will improve their sensitivity and specificity. Since thousands of protein/peptides will be identified and/or quantified, one important issue is to quantify and control the False Discovery Rate (# of false positive finding / # of selected markers as differentially expressed) and maintain reasonable power to detect truly differentially expressed markers. Another important feature of the data analysis is that the derived data from mass spectrometry critically depends on the algorithms of identifying the peptides, assigning protein identities and intensities. Coordinating center biostatisticians need work closely with proteomics bioinformaticians and computational biologists with expected iterations between data processing and data analyses.

Outcome

A pioneering collective discovery project using colon cancer pre-diagnostic plasma and controls is proposed as a joint Early Detection Research Network-Women’s Health Initiative (EDRN-WHI) study. One half ml of plasma from 100 colon cancer cases and an equal number of pair matched controls from the Observational Study (OS) will be aliquotted and made available by WHI for analysis using complementary proteomic platforms to assess the potential of proteomics technologies to generate leads concerning early detection markers or risk prediction markers for colon cancer, and to compare and contrast findings between proteomic platforms. Colon cancer cases that occur within a span of 18 months following year-3 OS blood draw will be selected. The platforms considered will include the commonly used ‘peptide shotgun’ approach, a comprehensive, quantitative intact plasma protein approach, tumor antigen/autoantibody approaches, a peptide capture mass spectrometry approach, and glycoprotein enrichment approaches. In phase 1, which is expected to last six months, participating investigators will analyze their own data. However by the end of phase one investigators are expected to have deposited their data in a central database for integrated analysis. The data will be publicly accessible following publication. The NCI Early Detection Research Network is expected to contribute most of the funding needed for this project.

Publications

• Increased plasma levels of the APC-interacting protein MAPRE1, LRG1, and IGFBP2 preceding a diagnosis of colorectal cancer in women.

Biomarkers

• No biomarkers available at this time for this protocol.

Data Collections

• EDRN WHI Colon

Start Date

Jan 17 2006

Estimated Finish Date

Jan 17 2007

Finish Date

Jan 17 2008

Protocol ID

126

Protocol Type

Collaboration

Field of Research

Glycomics

Collaborative Group

G.I. and Other Associated Cancers Research Group

Cancer Types

• Malignant neoplasm of colon