Statistical properties of a two-stage model of carcinogenesis.

Some of the statistical properties of a simple two-stage model of carcinogenesis are explored. The implications of additive treatment effects versus independent treatment effects on the shape of the dose-response curve are considered. Response that is low-dose linear results in the cases where the mutation rates are affected by dose or in the cases where treatment changes the birth rate/death rate of initiated cells in an additive fashion. Independent treatment effects lead to non-low-dose linear response when the survival of initiated cells is affected by treatment. A computer simulation experiment was performed that examined the ability of animal carcinogenesis data to differentiate between various forms of this simple two-stage model. It is shown that animal carcinogenicity experiments do not contain enough data to adequately describe the difference between these two types of effects.