The purpose of this study is to identify genetic linkage markers for common colorectal cancer and polyps. This will enable the early identification of high risk individuals for primary prevention. First degree relatives of patients with colorectal cancer represent a known high risk group for premalignant adenomatous polyps and subsequent development of large bowel cancer. Linkage studies, by focusing research on specific loci in the genome, are vital in our attempts to identify the major genes predisposing to common colorectal cancer. This study will involve a major collaborative effort involving a variety of biomedical expertise in order to approach this problem comprehensively. This study will include three basic arms: 1) clinical component - gastroenterology and pathology expertise to identify, evaluate, and manage the index cases and relatives. 2) A family studies and linkage analysis component - a team of genetic epidemiologists, field workers and counselors to provide an integrated approach to family risk assessment and counseling, study management, and genetic analysis. This will include coordination of recruitment of index cases and family members, follow up, data collection and management, and formal genetic analysis. An important element will be effective counselling, to facilitate screening and improve compliance. Serum samples will be frozen and stored, and lymphoblastoid lines will be established on all members of families meeting the study criteria. This will allow us to perform specific genetic linkage studies with identified genetic markers as they become available, usually at the DNA level using restriction fragment length polymorphism technology. 3.) A biomarkers hypothesis testing component-basic scientists who will evaluate the tumors and peripheral blood of affected individuals, in order to identify useful markers, usually at the DNA level, to be used in evaluating the genetic risk of asymptomatic family members. By developing the methodologies to identify those at genetic risk in families and the population, the information generated by this study will allow us to decrease the morbidity of colorectal cancer by primary intervention.
