Page 17 - 20dynamics of cancer

2 CHAPTER 1

level: little more than the fact that progression seems to follow through
multiple stages. A divide separates multistage theory from the daily
work of cancer research.
The distance between theory and ongoing research arose naturally.
The theory follows from rates of component failures and age-specific
incidence in populations; most cancer research focuses on the mecha-
nistic and biochemical controls of particular components such as the
cell cycle, cell death, DNA repair, or nutrient acquisition. It is not easy
to tie failure of a particular pathway in cell death to an abstract notion
of the rate of component failure and advancement by a stage in cancer
progression.
In this book, I work toward connecting the great recent progress in
molecular and cellular biology to the bigger problem: how failures in
molecular and cellular components determine rates of progression and
the age-specific incidence of cancer. I also consider how one can use
observed shifts in age-specific incidence to analyze the importance of
particular molecular and cellular aberrations. Shifts in incidence curves
measure changes in failure rates; changes in failure rates provide a win-
dow onto the design of molecular and cellular control systems.

1.1 Aims

The age-specific incidence curve reflects the processes that drive dis-
ease progression, the inheritance of predisposing genetic variants, and
the consequences of carcinogenic exposures. It is easy to see that these
various factors must affect incidence. But it is not so obvious how
these factors alter measurable, quantitative properties of age-specific
incidence.
My first aim is to explore, in theory, how particular processes cause
quantitative shifts in age-specific incidence. That theory provides the
tools to develop the second aim: how one can use observed changes in
age-specific incidence to reveal the molecular, cellular, inherited, and
environmental factors that cause disease. Along the way, I will present
a comprehensive summary of observed incidence patterns, and I will
synthesize the intellectual history of the subject.
I did not arbitrarily choose to study patterns of age-specific incidence.
Rather, as I developed my interests in cancer and other age-related dis-
eases, I came to understand that age-specific incidence forms the nexus