The Evolution of Lifespan and Age-Dependent Cancer Risk

The Armitage-Doll multistage model of carcinogenesis refocused cancer science by postulating that carcinogenesis is driven by a sequence of genetic changes in cells. Age-dependent cancer incidence thus has been explained in terms of the time necessary for oncogenic mutations to occur. While the multistep nature of cancer evolution is well supported by evidence, the mutation-centric theory is unable to explain numerous phenomena, such as the disproportion between cancer frequency and animal body size and the scaling of cancer incidence with animal lifespan. Here we present a theoretical review of the current paradigm and discuss some fundamental evolutionary theory postulates that explain why cancer incidence is a function of lifespan and physiological, not chronological, aging.