Molecular Epidemiology of Colorectal Cancer

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DESCRIPTION (provided by applicant): The Molecular Epidemiology of Colorectal Cancer (MECC) study is a population-based case-control study that examines the contribution of genetic sequence variation and environmental factors to the risk, pathogenesis, and prognosis of colorectal cancer (CRC). CRC is the second leading cause of cancer death in the United States and the leading cause of cancer death in Israel. Epidemiologic risk factors for CRC are reasonably well described, yet the majority of CRC arises in individuals with no known risk factors other than older age. Low penetrance susceptibility alleles such as APC 11307K are likely to play an important role in the population dynamics of this complex disease, yet the genetic variation that contributes to CRC is largely unexplored. Thus the broad objective of the MECC study is to understand how classic epidemiologic factors and genetic variation are related to the risk, pathogenesis, and prognosis of CRC. Israel has a well-defined population structure that facilitates gene discovery, and the differences in the incidence of CRC among different populations within Israel provide an epidemiologic context to study environmental and genetic contributions to CRC. In this collaborative study between the University of Michigan and the National Center for Cancer Control at Carmel Medical Center in Haifa, Israel we plan to evaluate 2 hypotheses: 1) Clinical features, somatic molecular markers, and tumor expression profiles predict relapse-free survival, disease-specific survival, and overall survival, 2) Previously unrecognized genes contribute to the risk of colorectal cancer and can be identified using a whole genome association. These hypotheses will be evaluated through the following specific aims: 1) Discover novel prognostic factors for CRC recurrence and survival of the MECC cases using clinical, laboratory, and epidemiologic data in conjunction with expression profiles of snap frozen tumors, and 2) Complete a whole genome association study of CRC using 400,000 carefully selected single nucleotide polymorphism (SNPs) that are densely spaced in and around approximately 85% of all known human genes.