A nonhomogeneous two-stage model of carcinogenesis

In this paper we extend the Moolgavkar-Venzon-Knudson two-stage model into nonhomogeneous cases. The probability generating functions (PGF) of initiated cells and tumors are derived under very general conditions. Using these PGFs we then obtain expected incidence functions of tumor and provide an iterative procedure for computing probability distributions of tumors. These results can be used to take account of time-varying exposures to help identify etiologic agents and to assess their mechanisms of action in epidemiologic studies.