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| Introduction | |
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| Aims | |
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| How to Read | |
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| Chapter Summaries | |
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| Background | |
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| Age of Cancer Incidence | |
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| Incidence and Acceleration | |
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| Different Cancers | |
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| Childhood Cancers | |
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| Inheritance | |
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| Carcinogens | |
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| Sex Differences | |
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| Summary | |
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| Multistage Progression | |
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| Terminology | |
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| What Is Multistage Progression? | |
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| Multistage Progression in Colorectal Cancer | |
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| Alternative Pathways to Colorectal Cancer | |
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| Changes during Progression | |
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| What Physical Changes Drive Progression? | |
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| What Processes Change during Progression? | |
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| How Do Changes Accumulate in Cell Lineages? | |
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| Summary | |
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| History of Theories | |
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| Origins of Multistage Theory | |
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| A Way to Test Multistage Models | |
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| Cancer Is a Genetic Disease | |
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| Can Normal Somatic Mutation Rates Explain Multistage Progression? | |
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| Clonal Expansion of Premalignant Stages | |
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| The Geometry of Cell Lineages | |
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| Hypermutation, Chromosomal Instability, and Selection | |
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| Epigenetics: Methylation and Acetylation | |
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| Summary | |
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| Dynamics | |
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| Progression Dynamics | |
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| Background | |
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| Observations to Be Explained | |
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| Progression Dynamics through Multiple Stages | |
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| Why Study Quantitative Theories? | |
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| The Basic Model | |
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| Technical Definitions of Incidence and Acceleration | |
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| Summary | |
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| Theory I | |
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| Approach | |
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| Solution with Equal Transition Rates | |
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| Parallel Evolution within Each Individual | |
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| Unequal Transition Rates | |
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| Time-Varying Transition Rates | |
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| Summary | |
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| Theory II | |
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| Multiple Pathways of Progression | |
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| Discrete Genetic Heterogeneity | |
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| Continuous Genetic and Environmental Heterogeneity | |
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| Weibull and Gompertz Models | |
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| Weibull Analysis of Carcinogen Dose-Response Curves | |
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| Summary | |
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| Genetics of Progression | |
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| Comparison between Genotypes in Human Populations | |
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| Comparison between Genotypes in Laboratory Populations | |
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| Polygenic Heterogeneity | |
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| Summary | |
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| Carcinogens | |
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| Carcinogen Dose-Response | |
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| Cessation of Carcinogen Exposure | |
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| Mechanistic Hypotheses and Comparative Tests | |
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| Summary | |
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| Aging | |
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| Leading Causes of Death | |
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| Multistage Hypotheses | |
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| Reliability Models | |
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| Conclusions | |
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| Summary | |
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| Evolution | |
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| Inheritance | |
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| Genetic Variants Affect Progression and Incidence | |
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| Progression and Incidence Affect Genetic Variation | |
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| Few Common or Many Rare Variants? | |
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| Summary | |
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| Stem Cells: Tissue Renewal | |
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| Background | |
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| Stem-Transit Program of Renewal | |
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| Symmetric versus Asymmetric Stem Cell Divisions | |
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| Asymmetric Mitoses and the Stem Line Mutation Rate | |
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| Tissue Compartments and Repression of Competition | |
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| Summary | |
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| Stem Cells: Population Genetics | |
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| Mutations during Development | |
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| Stem-Transit Design | |
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| Symmetric versus Asymmetric Mitoses | |
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| Summary | |
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| Cell Lineage History | |
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| Reconstructing Cellular Phylogeny | |
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| Demography of Progression | |
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| Somatic Mosaicism | |
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| Summary | |
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| Conclusions | |
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| Appendix: Incidence | |
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| References | |
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| Author Index | |
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| Subject Index | |