Multistage models of carcinogenesis.

The simple multistage model of carcinogenesis is outlined. It provides a satisfactory explanation of the power law for the age incidence of many forms of epithelial carcinoma, for the effects in human populations of changing exposures to supposed carcinogenic agents, and for many of the observed effects of applied carcinogens in animal experiments. In particular, the evidence on the effects of starting and stopping cigarette smoking suggests that both an early and a late stage may be affected. In the absence of direct evidence on the nature of the cellular changes there is some reluctance to accept a model with more than two stages, and several forms of two-stage models provide good general explanations of observed phenomena. Such a model has recently been applied to breast cancer; another approach to this disease, effectively involving transformations of the time scale, is discussed.