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Carcinogenesis Advance Access originally published online on September 14, 2006
Carcinogenesis 2007 28(2):479-487; doi:10.1093/carcin/bgl173
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© The Author 2006. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Stochastic modelling of colon cancer: is there a role for genomic instability?

Mark P. Little* and Guangquan Li

Department of Epidemiology and Public Health, Imperial College Faculty of Medicine London W2 1PG, UK

*To whom all correspondence should be addressed. Tel: +44 0 20 7594 3312; Fax: +44 0 20 7402 2150; Email: mark.little{at}imperial.ac.uk

Three stochastic models of genomic instability recently developed by Little and Wright (Math. Biosci., (2003) 183, 111–34), with two, three and five stages, and the two-stage genomic instability model of Nowak et al. (Proc. Natl Acad. Sci. USA, (2002) 99, 16226–16231) are compared with the four-stage model proposed by Luebeck and Moolgavkar (Proc. Natl Acad. Sci. USA, (2002) 99, 15095–15100) that does not assume such an instability mechanism. All models are fitted to US colon cancer incidence data. The best fitting models are the two-stage model of Nowak et al. and the two-stage model of Little and Wright, with the four-stage model of Luebeck and Moolgavkar not markedly inferior. The fits of the three-stage and five-stage models are somewhat worse (P < 0.05), the five-stage model fitting particularly poorly (P < 0.01). Both optimal genomic instability models predict cellular mutation rates that are at least 10 000 times higher after genomic destabilization, for both sexes. Therefore, the results of this paper are somewhat at variance with those of previous analyses of Little and Wright in suggesting that equivalently good fit may be obtained by models that do not assume a role for genomic destabilization in the induction of colon cancer as for those that do.

Abbreviations: AIC, Akaike information criterion; APC, adenomatous polyposis coli; CIN, chromosomal instability; GI, genomic instability; HNPCC, hereditary non-polyposis colon cancer; MIN, microsatellite instability; SEER, Surveillance, Epidemiology and End Results.

Received April 12, 2006; revised August 4, 2006; accepted September 2, 2006.


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