Page 33 - 20dynamics of cancer

18 CHAPTER 2

The fourth section turns to incidence patterns in individuals that
carry a strong genetic predisposition to cancer. Individuals carrying
a mutation in the APC gene have colon cancer at a rate about three to
four orders of magnitude higher than normal individuals, causing most
of the susceptible individuals to suffer cancer by midlife. Susceptible
individuals have an acceleration curve similar in shape to normal indi-
viduals, but shifted about 25 years earlier and slightly lower in average
acceleration. Individuals carrying an Rb mutation have retinoblastoma
at a rate about five orders of magnitude greater than normal individuals.
This difference is consistent with the theory that two Rb mutations are
the rate-limiting steps in transformation for this particular cancer, the
susceptible individuals already having one of the necessary two steps.
The fifth section discusses how carcinogens alter the incidence of can-
cer at different ages. The best data on human cancers come from stud-
ies of people who quit smoking at different ages. Longer duration of
smoking strongly increases the incidence of lung cancer. Interestingly,
among nonsmokers, the acceleration of cancer does not change as indi-
viduals grow older, whereas among smokers, the acceleration tends to
rise in midlife and then fall later in life. I also discuss incidence data
from laboratory studies that apply carcinogens to animals. These stud-
ies show remarkably clear relationships between incidence and dose.
Dose-response patterns provide clues about how mechanistic perturba-
tions to carcinogenesis shift quantitative patterns of incidence.
The sixth section examines the different patterns of incidence be-
tween the two sexes. Males have slightly more cancers early in life.
From approximately age 20 to 60, females have more cancers, mainly
because breast cancer rises in incidence earlier than the other major
adulthood cancers. After age 60, during the period of greatest cancer
incidence, males have more cancers than females, male incidence ris-
ing to about twice female incidence. The excess of male cancers late in
life occurs mainly because of sharp rises in male incidence for prostate,
lung, and colon cancers. Male cancers accelerate more rapidly with age
than do female cancers for lung, colon, bladder, melanoma, leukemia,
and thyroid. Female cancers accelerate more rapidly for the pancreas,
esophagus, and liver, but the results for those tissues are mixed among
samples taken from different countries.