Some mixed models of carcinogenesis (Q1118537)

The general mixed model of carcinogenesis considered by the author describes a population of \(k=k_ 1+k_ 2\) non-overlapping subpopulations involving \(k_ 1\) one-stage models and \(k_ 2\) two-stage models [Moolgavkar-Venzon-Knudson Model; see e.g. \textit{S. H. Moolgavkar}, Mathematics and computers in biomedical applications, Proc. IMACS Conf., 325-331 (1985; Zbl 0563.92003), and \textit{S. H. Moolgavkar} and \textit{D. J. Venzon}, Math. Biosci. 47, 55-77 (1979; Zbl 0422.92006)]. Biological evidence is shown by the application of mixtures of one-stage and two- stage models to carcinogenic processes related to oncogenes, anti oncogenes and accessory cancer genes. Basically it is assumed as in \textit{W. Y. Tan} and \textit{C. C. Brown}, Math. Modelling 9, 631-642 (1987; Zbl 0643.92016), that the normal stem cells and the intermediate cells follow a non-homogeneous birth-death process and that the mutation rates are age-dependent. Tumor cell growth is assumed to be instantaneously, and stochastic independence is required for all processes involved in the tumor development as well as between the process initiated by different cells. Using a probability generating function technique for the numbers of intermediate cells and tumor cells present at time t, expected incidence functions and probabilities of the number of tumors are derived if the number of initial stem cells \(N_ 0\) tends to infinity so that the product of \(N_ 0\) with the mutation rates remains finite. Important special cases, which are outlined analytically, are carcinogenesis for retinoblastoma and Wilm's tumor \((k_ 1=k_ 2=1),\) cancers involving accessory genes \((k_ 1=0,k_ 2=3)\), and the case of normal stem cells becoming immortatized by loss of differentiation capability.