Buch, Englisch, 400 Seiten, Format (B × H): 156 mm x 234 mm, Gewicht: 597 g
Incidence, Inheritance, and Evolution
Buch, Englisch, 400 Seiten, Format (B × H): 156 mm x 234 mm, Gewicht: 597 g
Reihe: Princeton Series in Evolutionary Biology
ISBN: 978-0-691-13366-9
Verlag: Princeton University Press
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.
Autoren/Hrsg.
Fachgebiete
- Naturwissenschaften Biowissenschaften Biowissenschaften DNA und Transgene Organismen
- Medizin | Veterinärmedizin Medizin | Public Health | Pharmazie | Zahnmedizin Klinische und Innere Medizin Innere Medizin
- Medizin | Veterinärmedizin Medizin | Public Health | Pharmazie | Zahnmedizin Klinische und Innere Medizin Onkologie, Krebsforschung
Weitere Infos & Material
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
