Origins of Multistage Theory

Two different lines of thought developed the idea that cancer progresses through multiple stages. The first line arose from the observation that, in experimental animal studies, cancer often followed after sequential application of different chemical carcinogens. The second line arose from observations on the age-onset patterns of cancer, in which incidence often accelerates with age in a manner that suggests multiple stages in progression. In the 1920s, several laboratories began to apply...

Technical Definitions of Incidence and Acceleration

Two ways to characterize age-onset patterns play an important role in analyzing cancer data and studying theories of cancer progression. Incidence is the rate at which individuals develop cancer at particular ages. Acceleration is the change in incidence rates. For example, positive acceleration means that incidence increases with age. This section provides some technical details for the definitions of incidence and acceleration. One can get a rough idea of the main results without these...

Alternative Pathways to Colorectal Cancer

Approximately 15 percent of colorectal tumors do not have CIN or widespread chromosomal abnormalities Rajagopalan et al. 2003 . Instead, these tumors usually have mutations in their mismatch repair MMR system, a component of DNA repair Boland 2002 . Loss of MMR Figure 3.3 Genetic changes in HNPCC progression. Approximately 2-4 percent of colorectal cancers follow this pathway. Figure 3.3 Genetic changes in HNPCC progression. Approximately 2-4 percent of colorectal cancers follow this pathway....