Multiple-Mutation Theory of Carcinogenesis

Abstract

NEW life was given to the somatic mutation theory of carcinogenesis when it was recognized that not just one, but several mutations were probably required. Fisher and Hollomon¹ thought that a number of similar mutations in adjacent cells might initiate cancer, and deduced a law of the form ${(\text{age})}^{p^{–1}}$ for the rate of appearance of cancers in a population, with p being the number of cells in the critical size group. They arrived at a value of p near 7 from the mortality data. Muller² and Nordling³ thought that a number of successive mutations in the same cell might initiate cancer, and deduced a law of the same form, ${(\text{age})}^{p^{–1}}$, for the rate of appearance of cancers, with p ≈ 7 now being the number of mutations required in a single cell.