Page 169 - 20dynamics of cancer

154 CHAPTER 8

6 (a) 8 (b) 2 (c)
Incidence 4 2 X 10 -4 4 2 $LLA

1 R
1
0
10 20 40 80 22 32 42 22 32 42
Age

Figure 8.5 Age-specific incidence of inherited and sporadic colon cancer. (a
and b) These panels match the corresponding panels in Figure 8.4, with the
fitted incidence curves here forced to be linear by assumption. (c) The difference
in the log-log acceleration between sporadic and inherited cases, which is the
log-log slope of R (see Eq. (8.2)).

multistage theory apply broadly. The first prediction is qualitative: the
acceleration of sporadic cases should be greater than the acceleration
of inherited cases. The second prediction is quantitative: if inherited
cases arise from a single mutation, then the difference in acceleration
between sporadic and inherited cases should be about one. My analyses
of retinoblastoma and the FAP form of inherited colon cancer support
both the qualitative and quantitative predictions.

8.2 Comparison between Genotypes
in Laboratory Populations

The previous sections compared the age of cancer onset between in-
dividuals with and without particular inherited mutations. Those in-
dividuals with inherited mutations progressed more quickly, at a rate
consistent with having passed at birth one stage in cancer progression.
Many lab studies with mice or rats compare the age-onset patterns
of cancer between different genotypes. Those studies usually focus on
whether particular mutations cause faster progression to cancer. In the
lab, one can control the environment and use animals that differ only
at particular loci. Such studies can provide a strong case for the causal
role of certain mutations in cancer progression.