Model for the incidence of embryonal cancers: application to retinoblastoma.

Abstract

The 2-mutation theory of human cancer initiation hypothesizes that some cancers originate after 2 successive mutations, of which the 2nd mutation is always somatic and the 1st mutation may be germinal (hereditary cases) or somatic (nonhereditary cases). A quantitative model using the Poisson distribution is developed for ages at diagnosis for hereditary and nonhereditary cases. This model relates age-specific incidence data to the number of divisions of embryonal cells and rates of somatic mutations per cell division. A good fit is obtained when the model is applied to data on ages at diagnosis for 1 such embryonal tumor, retinoblastoma.