) Inherited predispositions to specific cancers due to high penetrance alleles of genes such as APC and BRCA1 account for only a small percentage of our populations cancer burden. Genetic epidemiological evidence suggests, however, that a much higher percentage of individuals may be at risk due to the inheritance of alleles, or combinations of alleles, that individually show only a relatively low cancer penetrance. This makes it difficult to analyze the associated patterns of inheritance, localize the loci and identify the specific genes involved. Large sample populations are now required to map and identify these genes. We propose establishing a consortium consisting of the Universities of Colorado, New Mexico and Utah whose primary purpose will be to enroll a study population and create an infrastructure to support this next generation of exploration of the genetics of cancer. A population-based approach is needed to understand the population significance of future findings. State cancer registries provide an appropriate avenue of ascertainment. It is also important to develop a study population enriched for predisposed individuals. Our approach, therefore, is to ascertain individuals with one or more relatives who have been diagnosed with the specific cancer. Specifically, we propose initially to contact each individual diagnosed with breast, prostate, or colorectal cancer in calendar 1998 and 1999 and determine: 1) whether they are willing to participate and 2) have first-degree relatives affected with their same cancer. If so, they will be recontacted and asked to provide more detailed information regarding family history, as well as demographic and epidemiologic information. Selected index cases will be requested to complete questionnaires, which will include the names of their first-degree relatives and their permission to contact these relatives. The first-degree relatives will then be contacted and invited to enroll as members of the Cancer Genetics Network. This approach will create a study population of family members who have had cancer and who are at risk for cancer. We will also offer enrollment to appropriate individuals who have already contacted our high-risk clinics or are enrolled in ongoing clinical protocols of familial cancer; for example, Colorado will extend their current research interests by collecting lung cases. In addition, we will establish or enhance clinical and laboratory core facilities, as well as the necessary capabilities in genetic counseling, informatics and database management. As study groups are enrolled, DNA samples may be collected and pilot projects initiated; these include sib-pair studies and candidate-gene analysis funded by the Huntsman Cancer Institute and the University of Colorado Cancer Center.
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