Page 20 - 20dynamics of cancer

INTRODUCTION 5

the reaction grows too severe. The rest of the book applies the quan-
titative concepts of the mathematical chapters, but does so in a way
that can be read with nearly full understanding independently of the
mathematical details.
Chapters 8, 9, and 10 apply the quantitative theory to observed pat-
terns of age-specific incidence. I first test hypotheses about how inher-
ited, predisposing genotypes shift the age-specific incidence of cancer.
I then evaluate alternative explanations for the patterns of age-specific
cancer onset in response to chemical carcinogen exposure. Finally, I an-
alyze data on the age-specific incidence of the leading causes of death,
such as heart disease, cancer, cerebrovascular disease, and so on.
I then turn to various evolutionary problems. In Chapter 11, I evaluate
the population processes by which inherited genetic variants accumu-
late and affect predisposition to cancer. Chapters 12 and 13 discuss
how somatic genetic mutations arise and affect progression to disease.
For somatic cell genetics, the renewal of tissues through tissue-specific
adult stem cells plays a key role in defining the pattern of cell lineage
history and the accumulation of somatic mutations. Chapter 14 finishes
by describing empirical methods to study cell lineages and the accumu-
lation of heritable change.
The following section provides an extended summary of each chap-
ter. I give those summaries so that readers with particular interests
can locate the appropriate chapters and sections, and quickly see where
I present specific analyses and conclusions. The extended summaries
also allow one to develop a customized reading strategy in order to fo-
cus on a particular set of topics or approaches. Many readers will prefer
to skip the summaries for now and move directly to Chapter 2.

1.3 Chapter Summaries

Part I of the book provides background in three chapters: incidence,
progression, and conceptual foundations. Each chapter can be read in-
dependently as a self-contained synthesis of a major topic.
Chapter 2 describes the age-specific incidence curve. That failure
curve defines the outcome of particular genetic, cellular, and environ-
mental processes that lead to cancer. I advocate the acceleration of
cancer as the most informative measure of process: acceleration mea-
sures how fast the incidence (failure) rate changes with age. I plot the