Abstract

Many mouse models of colorectal cancer (CRC) have been developed, but the vast majority model familial forms of cancer. We have been exploiting a chemical model of colon cancer, azoxymethane (AOM) exposure, to model non-familial CRC . An extensive multi-strain comparison of the response to AOM -mediated tumorigenesis suggested genetic contribution to cancer, mirroring non-familial CRC in humans. We observed significant differences in susceptibility and In the present study, an extensive inbred strain profile was carried out using 39 inbred strains. A series of F1 and F2 crosses, and backcrosses between resistant and susceptible inbred strains in response to AOM showed a wide variety of strain differences in response to AOM and detailed analysis of inheritance patterns suggests that resistance to tumor development across populations is inherited in a dominant fashion. The model also revealed substantial genetic contribution to cancer morphology. Current studies are underway to identify biomarkers of susceptibility that can be used to identify the likelihood that an individual will develop cancer.