Page 41 - 20dynamics of cancer

26 CHAPTER 2

for particular kinds of genetic predisposition. Second, individuals with
genetic predisposition are often identified by their cancers or the can-
cers of family members, causing the sample of genetically predisposed
individuals to be biased and incomplete. Third, because we often do
not know the base population for individuals with particular genetic
tendencies, we usually cannot directly calculate incidence—the ratio of
cases relative to the total number of individuals with a particular genetic
predisposition over a particular time interval.
Studies vary in the extent to which they suffer from one or more of
these sampling problems. Measurements will improve as better genomic
techniques allow screening larger samples of individuals in an unbiased
way. For now, we can look at the existing studies to get a sense of what
patterns may arise.
The plots in Figures 2.4 and 2.5 use all individuals of a particular age
as the base population, measuring incidence as the number of cases di-
vided by the number of individuals in the base population. But many
of those cases arose among a small subpopulation of individuals who
carried particular genetic defects. It would be better to measure inci-
dence and acceleration against the correct base population of carriers
at risk for the disease. The following two examples show that, for high
penetrance inherited genetic defects that lead to particular cancers, one
can approximate the base population by assuming that a fixed fraction
of carriers eventually develops the disease (Frank 2005).
Familial adenomatous polyposis (FAP) occurs in individuals who carry
one mutated copy of the APC gene (Kinzler and Vogelstein 2002). This
form of colon cancer can be identified during examination and distin-
guished from sporadic colon cancers. Figure 2.6a,b compares the inci-
dence and acceleration for inherited and sporadic (nonfamilial) cases.
Retinoblastoma occurs as an inherited cancer in children who carry
one mutated copy of the Rb gene (Newsham et al. 2002). Inherited cases
often develop multiple tumors, usually at least one in each eye (bilateral).
Retinoblastoma also occurs as a sporadic cancer, usually with only a sin-
gle tumor in one eye (unilateral). Figure 2.6c,d compares the incidence
and acceleration for inherited and sporadic cases.
The comparison between inherited and sporadic forms illustrates the
role of genetics; the comparison between colon cancer and retinoblas-
toma illustrates the role of tissue development and the timing of cell
division. I will return to these data in later chapters, where I consider