  Most human carcinomas exhibit telomere abnormalities early in the
carcinogenesis process suggesting that crisis caused by telomere shortening may
be a necessary event leading to human carcinomas. Epidemiological records of
the age at which each patient in a population develops carcinoma are known as
age-incidence data; these provide a quantitative measure of human tumor
initiation and dynamics. If crisis brought on by telomere shortening is
necessary for most human carcinomas, it may also be the rate limiting step. To
test this, we compared a mathematical model in which telomere loss is the rate
limiting step during carcinogenesis with age-incidence data compiled by the
Surveillance, Epidemiology and End Results (SEER) program. We found that this
model adequately explains the age-incidence data. The model also implies that
two distinct paths exist for carcinoma to develop in prostate, breast, and
ovary tissues. We conclude that a single step, crisis brought on by telomere
shortening, limits the rate of formation of human carcinomas.
