Dynamics of Cancer: Incidence, Inheritance, and Evolution

Dynamics of Cancer: Incidence, Inheritance, and Evolution

by Steven A. Frank
     
 

"As Frank observes, 'Cancer is the failure of controls over cellular birth and death.' Although a vast amount of work has gone into describing the molecular and cellular processes involved, an understanding of the overall dynamics of these processes is less advanced. This book combines empirical information with insights into the nonlinear dynamics of multistage

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Overview

"As Frank observes, 'Cancer is the failure of controls over cellular birth and death.' Although a vast amount of work has gone into describing the molecular and cellular processes involved, an understanding of the overall dynamics of these processes is less advanced. This book combines empirical information with insights into the nonlinear dynamics of multistage progression, in ways that both illuminate and have practical implications. Anyone with serious interests in cancer research should read it."—Robert M. May, University of Oxford

"This is an excellent book on a very difficult but important subject. It does a superb job of introducing the various models for observed cancer frequencies and explaining their assumptions, conclusions, and weaknesses."—Darryl Shibata, University of Southern California

"This is a book of relentless scholarship, precise organization, and fundamental, interdisciplinary insights into the biology of cancer. It provides the first truly comprehensive theory for the epidemiological/genetic incidence curves that characterize cancer, the first solid integration of evolutionary genetics with cancer biology, and a rigorous, well-reasoned approach to progress in understanding the genetic and environmental bases of cancer."—Bernard Crespi, Simon Fraser University

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Product Details

ISBN-13:
9780691133669
Publisher:
Princeton University Press
Publication date:
07/02/2007
Series:
Princeton Series in Evolutionary Biology Series
Edition description:
New Edition
Pages:
400
Product dimensions:
6.10(w) x 9.10(h) x 1.10(d)

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

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