At least four genes and sex are associated with susceptibility to urethane-induced pulmonary adenomas in mice.

Susceptibility to urethane-induced lung adenomas in mice has a polygenic mode of inheritance, with no obvious discontinuity in lung tumour counts among 37 AXB recombinant inbred strains. However, mean tumour counts were markedly higher in strains carrying the A/J allele at the Kras2 and H2 complex than in those carrying the C57BL/ allele. In 162 F2 hybrids and small numbers of both backcrosses between strain A/J (susceptible) and C57/BL/6 (resistant) mice, five factors influencing susceptibility were identified. Variation due to the 'major' Kras2 locus (chromosome 6) accounted for 60% of the total variation. 'Minor' loci linked to microsatellite markers Tnfb (in the H2 complex), D9Mit11 and D19Mit16 (on chromosomes 17, 9 and 19, respectively) accounted for a further 13% of the variation, and males had more tumours than females with sex differences accounting for 2% of the variation. No significant association with 32 other loci was detected. On a square-root transformed scale, heterozygotes at all marker loci were of intermediate susceptibility compared with homozygotes. The three minor loci and sex only affected lung tumour counts when at least one susceptible Kras2 allele was present.