Cancer Dose-Response Models Incorporating Clonal Expansion
Under the assumption that a malignant tumor develops through a sequence of steps (normal cells → initiated cells/foci → nodules → tumors) two classes of mathematical models of carcinogenesis that have a potential to be used for cancer dose-response modeling are discussed. The two classes of models considered are (1) a general version of the two-stage model by Moolgavkar and colleagues [12, 13], henceforth called the MVK model, and (2) a clone process model derived from Tucker . These two classes of models incorporate essentially the same biological information but in different ways and offer a conceptual contrast between the two differing approaches. The objectives of this paper are to (1) highlight issues and problems that arise in using biologically based dose-response models to predict cancer risk and (2) discuss how parameters in the models could be estimated using auxiliary information.
We have also demonstrated that use of an approximate form of the MVK model may lead to a biologically unrealistic implication of the model and an underestimation of risk at low doses when parameters are estimated from bioassay data.
KeywordsHazard Function Vinyl Chloride Initiation Rate Cancer Risk Assessment Quantitative Risk Assessment
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