Complexity of lung cancer modifiers: mapping of thirty genes and twenty-five interactions in half of the mouse genome

genes control susceptibility to cancer in experimental animals, but the overall genetic information on this group of genes (i.e., number of loci and their mu-tual interactions) is missing. We per-formed a systematic search, scanning roughly half of the mouse genome for lung cancer susceptibility (Sluc) genes affecting tumor size or number by us-ing mouse recombinant congenic (RC) strains. In each RC strain (OcB), ap-proximately 12.5 % of the genome is de-rived from the lung cancer-resistant strain B10.O20, whereas the rest is de-rived from the lung cancer-susceptible strain O20. Methods: A total of 730 F2 hybrids from five (OcB × O20) crosses were tested. Pregnant mice were treated on day 18 of gestation with a single dose of N-ethyl-N-nitrosourea. When off-spring were 16 weeks old, whole lungs were removed and sectioned semiseri-ally, and the size of all lung tumors (n = 2658) was determined. Analysis of variance was used for detection of link-age, and models (including main effect and two-way interactions) were tested with a statistical program. Results: We detected a total of 30 Sluc loci (16 new plus 14 previously reported) and 25 two-way interactions. Some of these in-teractions are counteracting (e.g., Sluc17 and Sluc20), resulting in the partial or total masking of the indi-vidual independent effect (main effect) of each involved locus. Seven loc