Page 179 - 20dynamics of cancer

164 CHAPTER 8

If fast progressors have passed through all but the final stage in cancer
progression, and have only one stage remaining, then their annual risk
is constant—the risk is just the constant probability of passing the final
stage (Frank 2004d). By contrast, families with low genetic risk move
through the early stages slowly. In midlife, slow progressors typically
have more than one stage to pass, and so continue to have an increasing
rate of risk with advancing age.
The key questions concern what sort of genetic variants cause rela-
tively fast or slow progression, and how those genetic variants actually
affect the mechanisms and rates of progression. In a later chapter, I
discuss genetic variation in more detail. Based on the limited data cur-
rently available, one conclusion is that variants in DNA repair efficacy
may play an important role.

8.4 Summary

This chapter discussed inherited genetic predisposition to cancer in
light of multistage theory. Comparisons between genotypes provide the
strongest evidence for the role of particular genes in cancer progression.
Indeed, shifts in age-specific incidence may be the only way to measure
the consequences of particular genotypes on cancer, and quantitative
changes in progression dynamics may be the only way to evaluate the
relative importance of particular carcinogenic processes. The next chap-
ter applies the same methods of analysis to chemical carcinogens. The
observed shifts of age-specific incidence in response to carcinogens pro-
vide a window onto the processes of cancer progression.