Abstract B36: Modifier genes and cancer susceptibility: Lessons from inbred mouse strains

The adenomatous polyposis coli ( APC ) tumor suppressor gene is mutated in Familial Adenomatous Polyposis (FAP), an inherited disorder that predisposes individuals to developing intestinal polyposis and eventually leads to cancer. In the Min mouse model, the genetic background of mice carrying a mutation in the murine homolog of the APC gene ( Apc Min ) is critical to the manifestation of tumor phenotypes, as inbred strains have been demonstrated to differ dramatically in their susceptibility to polyposis. Complex trait analyses from several laboratories, including our own, have identified modifier loci that alter intestinal tumor number and size in Apc Min/+ mice, but less than a handful of modifier genes have been identified to date. We review the results of several quantitative trait loci (QTL) studies that have exploited the genomic diversity among inbred mouse strains and report the identification of novel modifier loci that protect against polyposis. We compare the results with cancer susceptibility loci identified through GWAS and other studies in the human genome. The usefulness of using the mouse as a model organism for optimizing complex trait screens for cancer phenotypes and speeding the process of causative gene identification is discussed. Research supported in part by NCI grants to LDS. Citation Format: Stephanie Nnadi, Xiang Wang, Richard C. Crist, Arthur M. Buchberg, Linda D. Siracusa. Modifier genes and cancer susceptibility: Lessons from inbred mouse strains. [abstract]. In: Proceedings of the AACR Special Conference: The Translational Impact of Model Organisms in Cancer; Nov 5-8, 2013; San Diego, CA. Philadelphia (PA): AACR; Mol Cancer Res 2014;12(11 Suppl):Abstract nr B36.