Page 44 - 20dynamics of cancer

AGE OF CANCER INCIDENCE 29

information about how particular genotypes affect the dynamics of pro-
gression. In later chapters, I show how to extract quantitative informa-
tion from the traditional survival plots and use that information to test
hypotheses about how genetic variants affect the dynamics of cancer
progression (Frank et al. 2005).

2.5 Carcinogens

Carcinogens alter age-specific incidence patterns. The extent to which
incidence patterns change depends on the dosage and the duration of
exposure, and also on the age at which an individual is exposed (Druck-
rey 1967; Peto et al. 1991). The ways in which carcinogens change age-
specific incidence may provide clues about the processes that cause can-
cer.
Most of the data on carcinogens come from studies of lab animals
because, of course, one cannot apply carcinogens to humans in a con-
trolled way. In later chapters, I will provide a more extensive discussion
of the experimental data on carcinogens in relation to various hypothe-
ses about the processes that lead to cancer. Here, I continue my empha-
sis on the patterns of incidence.
Figure 2.8 shows the best data available for carcinogen exposure in
humans: the effect on lung cancer of different durations of smoking.
As expected, the later the age at which individuals quit, the higher their
mortality (Figure 2.8a). Interestingly, the acceleration of lung cancer is
fairly constant for nonsmokers, with a slope of the log-log incidence
plot for nonsmokers of about four (Figure 2.8b). For those who smoke
until an age of at least 40 years, acceleration declines later in life; the
late-life decline in acceleration becomes steeper with a decrease in the
age at which individuals quit smoking.
Carcinogens applied to lab animals allow controlled measurement of
dosage and incidence. In the largest study, Peto et al. (1991) measured
the age-specific incidence of esophageal tumors in response to chronic
exposure to N-nitrosodiethylamine (NDEA). Exposure of inbred rats be-
gan at about six weeks of age and continued throughout life. The data
fit well to
I = nbt n−1 , (2.1)
where I is the standard measure of age-specific incidence, b is a constant
depending on dosage, t measures in years the duration of carcinogen