A multi-stage model of adenoma development

The overwhelming proportion of colorectal carcinomas are believed to origin ate as adenomatous polyps (adenomas), and the identification and removal of adenomas is an important component of colorectal cancer prevention efforts . Mathematical modeling of adenomas can increase our understanding of the n atural history and biology of adenomas and colorectal cancer and can help i n the effort to devise optimal prevention and screening strategies. Here we adapt the multi-stage model of carcinogenesis to the problem of the develo pment and growth of adenomas. We show that, using plausible values for the biological parameters, the model can fit various aspects of adenoma data in cluding adenoma prevalence by age, the size distribution of adenomas, clust ering of adenomas within individuals and the correlation between distal and proximal adenomas. Explaining the clustering of adenomas within individual s, as well as other findings, requires heterogeneity in risk in the populat ion; we show how such heterogeneity can be related to the distribution of b iological parameters in the population. The model can also be adapted to ac count for adenoma development in two major syndromes related to colorectal cancer, familial adenomatous polyposis and hereditary non-polyposis colorec tal cancer. (C) 2000 Academic Press.