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The book provides a unique conceptual and historical framework for understanding the causes of cancer and other diseases that increase with age. Using a novel quantitative framework of reliability and multistage breakdown, Frank unifies molecular, demographic, and evolutionary levels of analysis. He interprets a wide variety of observations on the age of cancer onset, the genetic and environmental causes of disease, and the organization of tissues with regard to stem cell biology and somatic mutation. Frank uses new quantitative methods to tackle some of the classic problems in cancer biology and aging: how the rate of increase in the incidence of lung cancer declines after individuals quit smoking, the distinction between the dosage of a chemical carcinogen and the time of exposure, and the role of inherited genetic variation in familial patterns of cancer.
Contents
- Chapter 1. Introduction
- Part I. Background
- Chapter 2. Age of Cancer Incidence
- Chapter 3. Multistage Progression
- 3.1 Terminology
- 3.2 What Is Multistage Progression?
- 3.3 Multistage Progression in Colorectal Cancer
- 3.4 Alternative Pathways to Colorectal Cancer
- 3.5 Changes during Progression
- 3.6 What Physical Changes Drive Progression?
- 3.7 What Processes Change during Progression?
- 3.8 How Do Changes Accumulate in Cell Lineages?
- 3.9 Summary
- Part II. Molecular Processes
- Chapter 4. History of Theories
- 4.1 Origins of Multistage Theory
- 4.2 A Way to Test Multistage Models
- 4.3 Cancer Is a Genetic Disease
- 4.4 Can Normal Somatic Mutation Rates Explain Multistage Progression?
- 4.5 Clonal Expansion of Premalignant Stages
- 4.6 The Geometry of Cell Lineages
- 4.7 Hypermutation, Chromosomal Instability, and Selection
- 4.8 Epigenetics: Methylation and Acetylation
- 4.9 Summary
- Chapter 5. Progression Dynamics
- Chapter 4. History of Theories
- Part III. Individual Interactions
- Part IV. Population Consequences
- Part V. Studying Evolution
- Chapter 15. Conclusions
- Appendix: Incidence
- References
- PDF version of this title (3.0M)
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