Commentary: The age distribution of cancer and a multistage theory of carcinogenesis.

The reversion of the incidence function to background rates is a mathematical consequence of multistage carcinogenesis. The third consequence has to do with the incidence of second malignant tumours among individuals in whom one has already occurred. A computation using the exact solution shows that the age-specific incidence of second malignant tumours is higher than the age-specific incidence of the first malignant tumour (at the same age). While the incidence of second malignant tumours is difficult to study in human populations because of the treatment intervention after the occurrence of the first tumour, animal experiments appear to show that this is indeed true. 13 The explanation has been advanced that physiological and immunological changes after the first malignancy renders the animal susceptible to a second tumour. This may be true but the higher incidence of second tumours is a logical consequence of multistage carcinogenesis. 14 It is a rare paper that continues to be widely cited 50 years after publication. The paper describing the Armitage-Doll model—often referred to as THE multistage model—is one such rare paper. I congratulate Professors Armitage and Doll on the occasion of the republication of this important and influential paper.