Abstract
Carcinogenesis is a multistage process driven by genetic damage and epigenetic changes. The classic view of two-stage carcinogenesis, in which tumor initiation (mutation) is followed by tumor promotion (epigenetic changes), has been conceptually important but is too simplistic. There may be six or more independent mutational events. Average annual agespecific cancer incidence rates from 1981 to 1985 reported by the SEER program are analyzed, and interpreted in accordance with a mathematical model which takes into consideration the number of events needed for tumor generation (n) and annual probability of occurrence of that event (p). Basically, cancer incidence rates are equated in terms of time as (1-(1-p)<sup>t</sup>)<sup>n</sup>. A genetic algorithm is used to find the minimum sum of squares. Overall, 4 to 8 events occur with an annual probability of 0.006 to 0.01. Specific data by site will be presented in tabular and graphical form.
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