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

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]

References

  1. ^ a b 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
  2. ^ Nordling, C. O. (1953) Brit. J. Cancer, 7, 68.
  3. ^ a b Ashley, D. J. B., Brit. J. Cancer, 23, 313 (1969)
  4. ^ 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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