Lay Summary

Proposal No. IBD-0065R
Principal Investigator: Randall F. Holcombe, M.D.
Applicant Organization: University of California, Irvine (U.S.A.)
Project Title: Wnt signaling in inflammatory bowel disease-related colon cancer
Period of Award: November 1, 2003 - October 31, 2005

These studies will define the role of Wnt signaling, and specifically the contributions of specific components of this signaling pathway, in inflammatory bowel disease (IBD) and IBD-associated colon cancers. Tissues for study will include paraffin-embedded, archived, pathologic samples from IBD patients who have had resection of a colon cancer, as well as fresh tissues obtained from IBD patients undergoing surveillance colonoscopy. In the latter, uninflamed, inflamed and dysplastic tissues, as well as any malignant tissue if present, will be evaluated. Tissues will be tested for the expression of important components of the Wnt pathway and for analysis of somatic mutations in particular genes important for regulating Wnt signaling. These data will be utilized to study the signaling specificity of particular subtypes of frizzled receptors and to define the genes regulated by this signaling.

These studies may lead to the identification of new prognostic markers and new modalities of early cancer detection for patients with IBD. They have the potential to define an objective modality for assisting in the differentiation between normal and dysplastic (pre-cancer) colonic mucosa. Understanding the role of these components of the Wnt pathway will contribute to knowledge required for the future development of novel, targeted prevention and therapeutic interventions for IBD patients who are at high risk for the development of colon cancer.