) The general objective of this application is to develop a population-based colorectal cancer (CRC) family registry resource, with epidemiologic data and a biologic tissue bank, from CRC patients in Ontario, Canada. The registry will be a contributor to the consortium of such registries planned by the National Institutes of Health (NIH) that will be used for epidemiologic studies, primary prevention trials, gene discovery; for the investigation of gene environment interactions; and for the evaluation of surveillance protocols and treatment interventions in high risk CRC families as part of a Co-operative Agreement with other family registries. This objective will be met by building on existing infrastructure and experience developed by co-investigators participating in the activities of the previously awarded Co-operative Family Registry for Breast Cancer Studies (CFRBCS), with which the CRC registry proposed here will be integrated. Further, the proposed Co-operative Family Registry for Colon Cancer Studies (CFRCCS) will take advantage of established resources, in particular the Ontario Cancer Genetics Network (OCGN) and the population-based Ontario Cancer Registry (OCR). The applicant plans to compile family history data for all eligible CRC cases in Ontario who will serve as probands, and family history information will be used to define cohorts of high risk according to the Amsterdam criteria and intermediate risk and sporadic cases and their families. Epidemiologic data, CRC treatment data and biologic tissues will be obtained from all high and intermediate risk probands and their families, from a random sample of sporadic cases (and a subsample of their families), and from population controls and a sample of their families. The frequency and nature of mutations in genes involved in hereditary predisposition to colon cancer in high and intermediate risk families will be determined. Molecular diagnostic testing will be performed on specimens from probands in these risk groups. The populations with hereditary predisposition to CRC identified by these activities will be potential participants in trials that evaluate new prevention and therapeutic strategies.
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