The overall impact of screening in Lynch Syndrome (LS) and Familial Colorectal Cancer type X families (FCCTX) (i.e. LS families with no mutation identified) remains uncertain. This uncertainty remains because methods are not yet available to study this problem and because a large number of families are needed to thoroughly understand it. In this project, we propose to evaluate the impact of screening on cancer occurrences and deaths in LS and FCCTX families and to identify the major factors affecting screening effectiveness. This research will address many important clinical issues affecting LS and FCCTX families: a) Estimate the risks of developing successive cancers among individuals who had and did not have screening given their mutation status; b) Identify and describe the poor responders to screening (e.g. individuals screened but who developed cancer); c) Provide realistic expectations about intervention responses over time; d) Characterize disease risk in the FCCTX families. e) Determine genetic risk in LS and FCCTX families using screening history and other known risk factors. This research project will provide appropriate guidelines for screening protocols in LS families and families who carry other disease genes in the US, Canada and around the world.