Epistatic interactions between skin tumor modifier loci in interspecific (spretus/musculus) backcross mice

The development of cancer is influenced both by exposure to environmental c arcinogens and by the host genetic background. Epistatic interactions betwe en genes are important in determining phenotype in plant and animal systems and are likely to be major contributors to cancer susceptibility in humans . Several tumor modifier loci have been identified from studies of mouse mo dels of human cancer, and genetic interactions between modifier loci have b een detected by genome scanning using recombinant congenic strains of mice (R, Fijneman et at, Nat, Genet,, 14: 465-467, 1996; T, van Wezel et al,, Na t, Genet,, 14: 468-470, 1996; W, N, Frankel at al,, Nat, Genet,, 14, 371-37 3, 1996), We demonstrate here that strong genetic interactions between skin tumor modifier loci can be detected by hierarchical whole genome scanning of a complete interspecific backcross [outbred Mus spretus X Mus musculus ( NIH/Ola)], A locus on chromosome 7 (Skts1) showed a highly significant inte raction with Skts5 on chromosome 12 (P < 10(-16)), whereas additional signi ficant interactions were detected between loci on chromosomes 4 and 5, and 16 and 15, Some of these quantitative trait loci and their interactions, in particular the Skts1-Skts5 interaction, were confirmed in two completely i ndependent backcrosses using inbred spretus strains (SEG/Pas and SPRET/Ei) and NIH/Ola, These results, therefore, illustrate the general use of inters pecific crosses between Mus musculus and Mus spretus for the detection of s trong genetic interactions between tumor modifier genes.