A subset of skin tumor modifier loci determines survival time of tumor-bearing mice

Studies of mouse models of human cancer have established the existence of m ultiple tumor modifiers that influence parameters of cancer susceptibility such as tumor multiplicity, tumor size, or the probability of malignant pro gression, We have carried out an analysis of skin tumor susceptibility in i nterspecific Mus musculus/ Mus spretus hybrid mice and have identified anot her seven loci showing either significant (six loci) or suggestive (one loc us) linkage to tumor susceptibility or resistance. A specific search was ca rried out for skin tumor modifier loci associated with time of survival aft er development of a malignant tumor. A combination of resistance alleles at three markers [D6Mit15 (Skts12), D7Mit12 (Skts2), and D17Mit7(Skts10)], ai l of which are close to or the same as loci associated with carcinoma incid ence and/or papilloma multiplicity, is significantly associated with increa sed survival of mice with carcinomas, whereas the reverse combination of su sceptibility alleles is significantly linked to early mortality caused by r apid carcinoma growth (chi(2) = 25.22; P = 5.1 x 10(-8)), These data indica te that host genetic factors may be used to predict carcinoma growth rate a nd/or survival of individual backcross mice exposed to the same carcinogeni c stimulus and suggest that mouse models may provide an approach to the ide ntification of genetic modifiers of cancer survival in humans.