The spindle assembly checkpoint is a mechanism that ensures that daughter cells inherit a balanced copy of the genetic material from the mother cell during cell division. Many genes are involved in this process and we have recently shown that a mutation in one of these genes was the cause of multiple gastrointestinal cancers in a man with several cancers. The aim of our proposal is to study whether mutations or misregulation of this and other important genes with closely related functions in the spindle assembly checkpoint (SAC) pathway also influence the risk of developing colorectal cancers in other patients. This will be accomplished as a case-control study using DNA and cell lines derived from colorectal cancer patients and unaffected individuals serving as controls. We believe this study will provide us with the opportunity to gain new insight into the mechanisms involved in the earliest stages of gastrointestinal carcinogenesis and could provide unique knowledge to help develop novel early diagnosis tools and treatments.