Biology:Armitage–Doll multistage model of carcinogenesis
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
[math]\displaystyle{ \mathrm{rate} = \frac{N p_1 p_2 p_3 \cdots p_r}{(r-1)!} t^{r-1} }[/math]
in Ashley's notation.[3]
Their interpretation was that a series of [math]\displaystyle{ r }[/math] 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 [math]\displaystyle{ r }[/math] 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]
References
- ↑ 1.0 1.1 Armitage, P. and Doll, R. (1954) "The Age Distribution of Cancer and a Multi-Stage Theory Of Carcinogenesis", British Journ. of Cancer, 8 (1), 1-12. Reprinted (2004): reprint, British Journal of Cancer, 91, 1983–1989. doi:10.1038/sj.bjc.6602297
- ↑ Nordling, C. O. (1953) Brit. J. Cancer, 7, 68.
- ↑ 3.0 3.1 Ashley, D. J. B., Brit. J. Cancer, 23, 313 (1969)
- ↑ Knudson, A.G., 1971. Mutation and cancer: statistical study of retinoblastoma. Proceedings of the National Academy of Sciences, 68(4), pp.820-823.
- Steven A Frank (2004) "Commentary: Mathematical models of cancer progression and epidemiology in the age of high throughput genomics", Int. J. Epidemiol. 33(6): 1179-1181 doi:10.1093/ije/dyh222
- Suresh H Moolgavkar (2004) "Commentary: Fifty years of the multistage model: remarks on a landmark paper", Int. J. Epidemiol. 33(6): 1182-1183 doi:10.1093/ije/dyh288
- Richard Doll (2004) "Commentary: The age distribution of cancer and a multistage theory of carcinogenesis", Int. J. Epidemiol. 33(6): 1183-1184 doi:10.1093/ije/dyh359
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