Model for the Incidence of Embryonal Cancers: Application to Retinoblastoma

The two-mutation theory of cancer initiation hypothesizes that some cancers originate after two successive mutations, of which the second mutation is always somatic and the first 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 explicitly to the number of divisions of embryonal cells and to rates of somatic mutations per cell division. A good fit is obtained when the model is applied to data on ages at diagnosis for one such embryonal tumor, retinoblastoma.