Synopses & Reviews
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.
Review
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.
Review
"This book 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 and the inheritance of predisposition to disease."--Biology Digest
Review
Frank is an evolutionary biologist with a strong mathematics bent. His book grapples with many...issues, offering insights from his mathematical modelling of various steps of tumour progression...One day he may be seen as the pioneer who began the difficult task of building a sturdy foundation for a truly useful mathematical model of cancer development. -- Robert A. Weinberg, Nature Frank's forte in the book is his search for the simplicity that is often masked by the complexities of cancer. With his mathematical models in hand, he turns to the details of cancer genetics, carcinogens, and aging and provides novel integrative insights...Dynamics of Cancer emphasizes both the multiscale dynamics of the disease and an approach that synthesizes empirical knowledge with parsimonious, mathematical theory. Frank moves the field forward, narrowing the gap between a tragic disease of everyday life and the Darwinian world of the genome. -- David C. Krakauer, Science This book 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 and the inheritance of predisposition to disease. -- Biology Digest 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
Review
"Frank is an evolutionary biologist with a strong mathematics bent. His book grapples with many...issues, offering insights from his mathematical modelling of various steps of tumour progression...One day he may be seen as the pioneer who began the difficult task of building a sturdy foundation for a truly useful mathematical model of cancer development."--Robert A. Weinberg, Nature
Review
"Frank's forte in the book is his search for the simplicity that is often masked by the complexities of cancer. With his mathematical models in hand, he turns to the details of cancer genetics, carcinogens, and aging and provides novel integrative insights...Dynamics of Cancer emphasizes both the multiscale dynamics of the disease and an approach that synthesizes empirical knowledge with parsimonious, mathematical theory. Frank moves the field forward, narrowing the gap between a tragic disease of everyday life and the Darwinian world of the genome."--David C. Krakauer, Science
Review
"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
Synopsis
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.
Synopsis
"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
Synopsis
"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
Synopsis
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.
Synopsis
"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
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).
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