Genes Controlling Susceptibility to Mammary Cancer.

Oral gavage with the carcinogen 7,l2-dimethylbenzAanthracene (DMBA) is reported to specifically cause mammary tumors in rats. This work examined the response of different genotypes of mice to this carcinogen. Mice demonstrate a genotypic specificity for the particular tumors that they develop; DMBA increase the incidence of and decreases the average age at which these tumors are manifest. It does not appear that the genetic instability of the sort associated with the Werner syndrome in humans appreciably enhances the predilection of mice to develop mammary cancer, even in mice dosed with the carcinogen DMBA. Increased adiposity is a risk factor for postmenopausal breast cancer in humans. Presented is work demonstrating that the dietary intervention of calorie restriction reduces the incidence of mammary tumors following carcinogen administration in genotypes predisposed to its development. It does not appear, however, that adiposity augmented beyond that obtained with ad libitum feeding increases mammary tumor incidence in mice. This work illustrates an aspect of mammary tumor carcinogenesis deserving of further investigation, namely, the fact that tumor incidence in genetically identical individuals maintained under identical environmental conditions is not 100% is strongly suggestive that there is a stochastic component involved in tumor development.