Studies of both spontaneous and chemically induced tumors have demonstrated that there is considerable variation among individuals in their response to carcinogenesis suggesting that genetic factors influence the likelihood of developing cancer. Although studies of familial cancer syndromes such as Wilms’ tumor, retinoblastoma and Li-Fraumeni syndrome have led to the discovery of tumor suppressor genes that directly contribute to tumor development, inheritance of such highly penetrant mutated genes accounts for only a small proportion of the overall incidence of cancer [1, 2]. Much epidemiological data suggest that cancer susceptibility in the general population is a function of multiple, poorly penetrant tumor susceptibility genes that control the propensity toward environmental carcinogen-induced tumor development. Animal models of genetic susceptibility for development of specific tumors have proved to be useful experimental tools for identifying and characterizing such genetic factors.

The notion that tumor susceptibility genes are encoded in the germline is supported by the striking variation in tumor incidence among different inbred strains of mice or rats exposed to the same chemical. The fact that the relative sensitivity or resistance of a given rodent strain is a heritable trait supports the premise that specific genes regulate susceptibility to tumor development. Tumor susceptibility genes that contribute to interstrain variance in development of carcinogen-induced lung, liver, colon, mammary, kidney, hematopoietic and skin tumors have been mapped by analyzing tumor development in segregating crosses of sensitive versus resistant mouse or rat strains [reviewed in 3]. For example, the complexity of genetic control of cancer