1.William Grady/Fred Hutchinson Cancer Center/University of Washington: Markers of Methylation
2.Sanford Markowitz/Ireland Cancer Center/Case Western Reserve: Vimentin and 15-PGDH
3.Robert Getzenberg/Johns Hopkins School of Medicine: Creatine Kinase B
4.Paul Lampe/Fred Hutchison Cancer Research Center: Proteomic Markers
5.Daniel C. Liebler: Vanderbilt University School of Medicine: Proteomic Markers
G.I. and Other Associated Cancers Research Group
The goal of this project is to evaluate biomarkers in normal colonic mucosa to determine their relationship to the occurrence of short- and long-term colorectal neoplasia. Candidate markers have been proposed by participating investigators based on promising preliminary data. The purpose of this team project is to evaluate these markers in a common, tissue-based reference set, under a uniform, structured protocol.
1. Characterization of intra-subject reproducibility and variability: To assess the reproducibility and variability of marker expression within individuals, we will evaluate marker expression in duplicate samples from the same region of the colon and in 4 different sites around the colon, the rectum, left, transverse and right colon.
2. Characterization of inter-subject variability in marker expression by disease phenotype: To characterize the inter-subject variability in marker expression by disease phenotype, we will compare marker expression in normal colonic mucosa between subjects with and without adenomatous polyps.
3. Characterization of the relationship of marker expression and long-term adenoma recurrence: To examine the relationship between marker expression and long-term adenoma recurrence, we will compare marker expression among subjects with baseline adenomas who have a recurrence of adenomatous polyps compared to those who do not.
Analysis Plan: A mixed effects linear model will be used to estimate means and between-patient and within-segment variance parameters; location of biopsy will be considered a fixed effect, and patient a random effect. The within-segment variance is an estimator of assay reliability, while the difference in means between segments indicates how well rectal or distal colon values agree with transverse and proximal colon values. The between-patient variances can be used to calculate effect sizes used in the design of subsequent trials. The biopsy location effect is an indicator of the consistency of the biomarkers throughout the colon; because these are normal tissue, not adenoma, biopsies, significant variation between biopsy sites would have implications for sampling strategies, and could indicate non-specificity of the marker for adenoma. Using Monte Carlo simulation of the proposed design, we determined that, in 90% of the simulated trials, the estimated between-patient variance was within 70% of the true value, and the estimated within-segment variance was within 28% of its true value. The power to test the null hypothesis of no difference in means between segments was in excess of 80% if the effect size (difference between segment means divided by within-segment standard deviation) was 0.8 or greater.
There are currently no biomarkers annotated for this protocol.
No datasets are currently associated with this protocol.