Page 42 - 20dynamics of cancer

AGE OF CANCER INCIDENCE 27

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Figure 2.6 Comparison of incidence and acceleration between inherited and
sporadic cancers. Incidence is given as log 10 of the number of cases per one
million population per year. Solid lines show inherited forms; dashed lines show
sporadic forms. (a,b) I calculated FAP incidence by analyzing the age distribu-
tion of 129 cases combined for males and females as summarized in Ashley
(1969a), from data originally presented by Veale (1965). Mutated APC alleles
have very high penetrance for FAP, so the incidence at each age can be measured
as the number of cases in an age interval divided by the fraction of individuals
who had not developed the disease at earlier ages and ultimately did develop
the disease. For the sporadic form, I used the incidence of colorectal cancers
from the SEER database combined for white males and females from the period
1973–1977. (c,d) Inherited and sporadic forms of retinoblastoma. For the in-
herited form, I used 221 reported bilateral cases taken directly from the SEER
database for 1973–2001. To estimate age-specific incidence, I assumed that
65 percent of carriers eventually developed bilateral tumors, based on the es-
timated penetrance for bilateral retinoblastoma given in Knudson (1971). The
incidence in each year is approximately the fraction of cases in that year di-
vided by the fraction of individuals in the sample who had not developed the
disease in earlier years. For the sporadic form, I used the reported incidence
of unilateral cases in Young et al. (1999), which is also from the SEER database.
However, the SEER data do not differentiate between sporadic and hereditary
unilateral cases. Based on Knudson (1971), about 75 percent of unilateral cases
are sporadic cancers and about 25 percent arise from carriers who inherit a
mutation. Incidence plots (a,c) from Frank (2005).