Armitage–Doll multistage model of carcinogenesis
Statistical model in biology
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The Armitage–Doll model is a statistical model of carcinogenesis, proposed in 1954 by Peter Armitage and Richard Doll, in which a series of discrete mutations result in cancer.[1] The original paper has recently been reprinted with a set of commentary articles.
The model
The rate of incidence and mortality from a wide variety of common cancers follows a power law: someone's risk of developing a cancer increases with a power of their age.[2]
The model is very simple, and reads
in Ashley's notation.[3]
Their interpretation was that a series of mutations were required to initiate a tumour.[1] This is now widely accepted, and part of the mainstream view of carcinogenesis. In their original paper, they found that was typically between 5 and 7. Other cancers were later discovered to require fewer mutations: retinoblastoma, typically emerging in early childhood, can emerge from as few as 1 or 2, depending on pre-existing genetic factors.
History
This was some of the earliest strong evidence that cancer was the result of an accumulation of mutations. With their 1954 paper, Armitage and Doll began a line of research that led to Knudson's two-hit hypothesis and thus the discovery of tumour suppressor genes.[3][4]
