Multistage carcinogenesis and radiation.

We will briefly review the concept of multistage carcinogenesis and the mathematical models built on this idea, including a class of models recently developed to describe the pathogenesis of colon cancer. The simplest model that explicitly accounts for cell proliferation kinetics is the two-stage clonal expansion model. It has been applied to a number of experimental and epidemiological data sets and has generated several thought-provoking hypotheses, especially as they relate to the role of promotion in radiation-induced carcinogenesis. The model generates hazard functions (used to estimate age-specific cancer incidence) that are not always intuitive because of the stochastic nature of the clonal expansion process involved. However, the model does make specific predictions depending on whether initiation, promotion or malignant conversion is affected by a carcinogen. A recent analysis of a large cohort of radiation workers exemplifies this behaviour.