Dynamics of Cancer: Incidence, Inheritance, and Evolution by Steven A. FrankDynamics of Cancer: Incidence, Inheritance, and Evolution by Steven A. Frank

Dynamics of Cancer: Incidence, Inheritance, and Evolution

bySteven A. Frank

Paperback | July 22, 2007

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The onset of cancer presents one of the most fundamental problems in modern biology. In Dynamics of Cancer, Steven Frank produces the first comprehensive analysis of how particular genetic and environmental causes influence the age of onset.


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.


This is the only book that presents a full analysis of the age of cancer onset. It is a superb teaching tool and a rich source of ideas for new and experienced researchers. For cancer biologists, population geneticists, evolutionary biologists, and demographers interested in aging, this book provides new insight into disease progression, the inheritance of predisposition to disease, and the evolutionary processes that have shaped organismal design.

About The Author

Steven A. Frank is professor of biology at the University of California, Irvine. He is the author of Immunology and Evolution of Infectious Disease and Foundations of Social Evolution (both Princeton).
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Details & Specs

Title:Dynamics of Cancer: Incidence, Inheritance, and EvolutionFormat:PaperbackDimensions:400 pages, 9.25 × 6 × 0.68 inPublished:July 22, 2007Publisher:Princeton University PressLanguage:English

The following ISBNs are associated with this title:

ISBN - 10:0691133662

ISBN - 13:9780691133669

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Extra Content

Table of Contents

Chapter 1: Introduction 1

1.1 Aims 2

1.2 How to Read 4

1.3 Chapter Summaries 5





PART I: BACKGROUND





Chapter 2: Age of Cancer Incidence 17

2.1 Incidence and Acceleration 19

2.2 Different Cancers 20

2.3 Childhood Cancers 23

2.4 Inheritance 25

2.5 Carcinogens 29

2.6 Sex Differences 32

2.7 Summary 35





Chapter 3: Multistage Progression 36

3.1 Terminology 37

3.2 What Is Multistage Progression? 38

3.3 Multistage Progression in Colorectal Cancer 39

3.4 Alternative Pathways to Colorectal Cancer 43

3.5 Changes during Progression 49

3.6 What Physical Changes Drive Progression? 50

3.7 What Processes Change during Progression? 51

3.8 How Do Changes Accumulate in Cell Lineages? 55

3.9 Summary 58





Chapter 4: History of Theories 59

4.1 Origins of Multistage Theory 61

4.2 A Way to Test Multistage Models 65

4.3 Cancer Is a Genetic Disease 69

4.4 Can Normal Somatic Mutation Rates Explain Multistage Progression? 71

4.5 Clonal Expansion of

Premalignant Stages 74

4.6 The Geometry of Cell Lineages 76

4.7 Hypermutation, Chromosomal Instability, and Selection 78

4.8 Epigenetics: Methylation and Acetylation 79

4.9 Summary 80





PART II: DYNAMICS





Chapter 5: Progression Dynamics 85

5.1 Background 86

5.2 Observations to Be Explained 89

5.3 Progression Dynamics through Multiple Stages 90

5.4 Why Study Quantitative Theories? 93

5.5 The Basic Model 93

5.6 Technical Definitions of Incidence and Acceleration 94

5.7 Summary 95





Chapter 6: Theory I 96

6.1 Approach 97

6.2 Solution with Equal Transition Rates 97

6.3 Parallel Evolution within Each Individual 100

6.4 Unequal Transition Rates 103

6.5 Time-Varying Transition Rates 109

6.6 Summary 114





Chapter 7: Theory II 115

7.1 Multiple Pathways of Progression 116

7.2 Discrete Genetic Heterogeneity 120

7.3 Continuous Genetic and Environmental Heterogeneity 129

7.4 Weibull and Gompertz Models 136

7.5 Weibull Analysis of Carcinogen Dose-Response Curves 139

7.6 Summary 142





Chapter 8: Genetics of Progression 143

8.1 Comparison between Genotypes in Human Populations 144

8.2 Comparison between Genotypes in Laboratory Populations 154

8.3 Polygenic Heterogeneity 160

8.4 Summary 164





Chapter 9: Carcinogens 165

9.1 Carcinogen Dose-Response 166

9.2 Cessation of Carcinogen Exposure 180

9.3 Mechanistic Hypotheses and Comparative Tests 190

9.4 Summary 201





Chapter 10: Aging 202

10.1 Leading Causes of Death 203

10.2 Multistage Hypotheses 206

10.3 Reliability Models 207

10.4 Conclusions 209

10.5 Summary 209





PART III: EVOLUTION





Chapter 11: Inheritance 213

11.1 Genetic Variants Affect Progression and Incidence 214

11.2 Progression and Incidence Affect Genetic Variation 234

11.3 Few Common or Many Rare Variants? 243

11.4 Summary 250





Chapter 12: Stem Cells: Tissue Renewal 251

12.1 Background 252

12.2 Stem-Transit Program of Renewal 253

12.3 Symmetric versus Asymmetric Stem Cell Divisions 264

12.4 Asymmetric Mitoses and the Stem Line Mutation Rate 265

12.5 Tissue Compartments and Repression of Competition 269

12.6 Summary 270





Chapter 13: Stem Cells: Population Genetics 271

13.1 Mutations during Development 272

13.2 Stem-Transit Design 280

13.3 Symmetric versus Asymmetric Mitoses 283

13.4 Summary 285





Chapter 14: Cell Lineage History 286

14.1 Reconstructing Cellular Phylogeny 287

14.2 Demography of Progression 295

14.3 Somatic Mosaicism 304

14.4 Summary 308





Chapter 15: Conclusions 309





Appendix: Incidence 314

References 335

Author Index 361

Subject Index 373


Editorial Reviews

"It will be highly interesting to a wide readership, including students who would like to learn about this subject, theoretical/mathematical biologists, epidemiologists, and molecular/clinical cancer biologists. Although the volume is based on mathematical theory, the excellent writing style ensures that it can be read both by biologists with no background in mathematics, and by theoreticians who would like to learn more about the dynamics that govern cancer initiation and progression."--Dominik Wodarz, Quarterly Review of Biology