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

edit

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

edit

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

edit
  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