Analysis of cancer incidence data on the basis of multistage and clonal growth models.

Publisher Summary This chapter compares the ability of multistage and clonal growth models for carcinogenesis to fit the cancer incidence/age profiles. It could well be, however, that the two models should not be so sharply distinguished. Indeed, the two may be unrealistic and unrealizable extremes of a continuum of mechanisms, all of which are really multistage and clonal growth processes. The two stages in carcinogenesis as the initiation and then the promotion of cancer, does not negate the possibility of further and clinically important progression of cancer. The chapter presents comparison figures in which two-stage, three-mutation models are fitted to the cancer incidence data and where these same data are fitted by the two-stage, two-mutation model that shows how difficult it will be to kinetically distinguish between these alternatives. Similarly, the multistage models in their pure form cannot be considered as realistic. It is far more realistic to assume that it is this cell and its descendants that are subject to the possibility of the fourth mutation. Indeed, it is necessary to assume this, since it is only during cell division that a thrice-mutated cell is at the risk of mutating once again. The arguments taken together should therefore be seen as supporting a multistage, clonal growth model rather than any extreme case on a continuum of such models.