Epidemiologic evidence for multi‐stage theory of carcinogenesis

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Abstract
A multi‐stage model of carcinogenesis is proposed assuming time homogeneous transition intensities from stage to stage. The model shows a fairly close agreement with the observed age incidence curves, not only for epithelial tumors, but also for tumors showing a more irregular age pattern. The model is applied to throw light on the mechanisms of carcinogenesis. Selected primary sites are considered and it is proposed that tumors of peripheral nerves in children and young adults are a result of a single change or hit, acute leukemia in children is probably a two‐hit disease, whereas most tumors of epithelial origin require several changes. Tumors with a bimodal incidence curve, like Hodgkin's disease and breast cancer, are likely to consist of two entities.It is stressed that the assumption of constant transition intensities may not be true, especially in regard to tumors with conceivably long periods of exposure.Different incidence patterns have required different interpretations on the mechanisms of carcinogenesis. The model presented in this paper provides a synthetic explanation for the genesis of different types of tumors with apparently different shapes in the age‐specific incidence curves.

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