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Epigenetics and Human Health

Linking Hereditary, Environmental and Nutritional Aspects
1. Aufl.

von: Alexander Haslberger, Sabine Greßler
142,99 €
Verlag:	Wiley-Blackwell
Format:	PDF
Veröffentl.:	24.09.2009
ISBN/EAN:	9783527628391
Sprache:	englisch
Anzahl Seiten:	316

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Beschreibungen

Titelbeschreibung

After first introducing the concept of epigenetics, this handbook and ready reference provides an overview of the main research on epigenetics. It adopts a multidisciplinary approach, involving molecular biology, molecular epidemiology and nutritional science, with a special focus of the book is on disease prevention and treatment. Of interest to all healthcare-related professionals as well as nutritionists, and the medical community focusing on disease prevention.

Inhaltsverzeichnis

Preface xv List of Contributors xvii Part I General Introduction 1 The Research Program in Epigenetics: The Birth of a New Paradigm 3 Paolo Vineis References 5 2 Interactions Between Nutrition and Health 7 Ibrahim Elmadfa 2.1 Introduction 7 2.2 Epigenetic Effects of the Diet 8 2.3 Current Nutrition Related Health Problems 8 References 9 3 Epigenetics: Comments from an Ecologist 11 Fritz Schiemer References 12 4 Interaction of Hereditary and Epigenetic Mechanisms in the Regulation of Gene Expression 13 Thaler Roman, Eva Aumüller, Carolin Berner, and Alexander G. Haslberger 4.1 Hereditary Dispositions 13 4.2 The Epigenome 14 4.3 Epigenetic Mechanisms 15 4.3.1 Methylation 15 4.3.2 Histone Modifications 18 4.3.3 Micro RNAs 20 4.4 Environmental Influences 20 4.4.1 Nutritional and Environmental Effects in Early Life Conditions 20 4.4.2 Environmental Pollution and Toxins 22 4.5 Dietary Effects 22 4.5.1 Nutrition and the Immune System 26 4.5.2 Nutrition and Aging 26 4.6 Inheritance and Evolutionary Aspects 28 4.7 Conclusion 29 References 30 Part II Hereditary Aspects 5 Methylenetetrahydrofolate Reductase C677T and A1298C Polymorphisms and Cancer Risk: A Review of the Published Meta-Analyses 37 Stefania Boccia 5.1 Key Concepts of Population-Based Genetic Association Studies 37 5.1.1 Definition and Goals of Genetic Epidemiology 37 5.1.2 Study Designs in Genetic Epidemiology 38 5.1.3 The Human Genome 38 5.1.4 Meta-Analysis in Genetic Epidemiology 39 5.1.5 Human Genome Epidemiology Network 40 5.1.6 “Mendelian Randomization” 41 5.2 Methylenetetrahydrofolate Reductase Gene Polymorphisms (C677T and A1298C) and Its Association with Cancer Risk 41 5.2.1 Gene and Function 41 5.2.2 C677T and A1298C Gene Variants 43 5.2.3 Gene–Environment Interaction 43 5.3 Meta-Analyses of Methylenetetrahydrofolate Reductase C677T and A1298C Polymorphisms and Cancer 44 References 47 6 The Role of Biobanks for the Understanding of Gene–Environment Interactions 51 Christian Viertler, Michaela Mayrhofer, and Kurt Zatloukal 6.1 Background 51 6.1.1 What Purpose Do Different Biobank Formats Serve? 52 6.1.2 Why Do We Need Networks of Biobanks? 53 6.2 The Investigation of Gene–Environment Interactions as a Challenge for Biobanks 55 6.2.1 How to Evaluate Risk Factors for Metabolic Syndrome and Steatohepatitis? 58 6.2.2 Why Are Biobanks Needed in This Context and What Challenges Do They Have to Face? 58 References 60 7 Case Studies on Epigenetic Inheritance 63 Gunnar Kaati 7.1 Introduction 64 7.2 Methodology 65 7.2.1 On the Study of Epigenetic Inheritance 65 7.2.2 The Ideal Study Design 66 7.2.3 The Överkalix Cohorts of 1890, 1905 and 1920 67 7.2.4 The ALSPAC Data Set 68 7.2.5 The Proband’s Childhood 68 7.2.6 Food Availability 69 7.2.7 Ancestors’ Experience of Crises 69 7.2.8 Growth Velocity 69 7.3 Patterns of Transgenerational Responses 70 7.3.1 The Social Context 70 7.3.2 The Ancestors’ Nutrition 71 7.3.3 Longevity and Paternal Ancestors’ Nutrition 71 7.3.4 The Influence of Nutrition During the Slow Growth Period on Cardiovascular and Diabetes Mortality 72 7.3.5 Is Human Epigenetic Inheritance Mediated by the Sex Chromosomes? 73 7.3.5.1 Paternal Initiation of Smoking and Pregnancy Outcome 75 7.3.6 Epigenetic Inheritance, Early Life Circumstances and Longevity 75 7.3.7 How to Explain the Effects of Food Availability During SGP on Human Health? 76 7.3.7.1 Genetic Selection Through Differential Survival or Fertility? 76 7.3.7.2 Chromosomal Transmission of Nutritionally Induced Epigenetic Modifications 76 7.4 Epigenetic Inheritance 77 7.4.1 Fetal Programming and Epigenetic Inheritance 78 7.5 Future Directions 80 7.6 Conclusions 81 References 83 Part III Environmental and Toxicological Aspects 8 Genotoxic, Non-Genotoxic and Epigenetic Mechanisms in Chemical Hepatocarcinogenesis: Implications for Safety Evaluation 89 Wilfried Bursch 8.1 Introduction 90 8.2 Genotoxic and Non-Genotoxic Chemicals in Relation to the Multistage Model of Cancer Development 91 8.2.1 Tumor Initiation 91 8.2.2 Tumor Promotion 92 8.2.3 Tumor Progression 93 8.2.4 Cellular and Molecular Mechanisms of Tumor Initiation and Promotion 93 8.2.5 Epigenetic Effects of Genotoxic and Non-Genotoxic Hepatocarcinogens 96 8.2.6 How Carcinogens Alter the Microenvironment – Crucial Roles of Inflammation 97 8.3 Concluding Remarks 97 References 99 9 Carcinogens in Foods: Occurrence, Modes of Action and Modulation of Human Risks by Genetic Factors and Dietary Constituents 105 M. Mišík, A. Nersesyan, W. Parzefall, and S. Knasmüller 9.1 Introduction 105 9.2 Genotoxic Carcinogens in Human Foods 106 9.2.1 Polycyclic Aromatic Hydrocarbons 107 9.2.2 Nitrosamines 107 9.2.3 Heterocyclic Aromatic Amines (HAAs) and Other Thermal Degradation Products 108 9.2.4 Mycotoxins 109 9.2.5 Food Additives and Carcinogens in Plant-Derived Foods 109 9.2.6 Alcohol 111 9.3 Contribution of Genotoxic Dietary Carcinogens to Human Cancer Risks 111 9.4 Protective Effects of Dietary Components Towards DNA-Reactive Carcinogens 112 9.5 Gene Polymorphisms Affecting the Metabolism of Genotoxic Carcinogens 114 9.6 Concluding Remarks, Epigenetics and Outlook 118 References 118 Part IV Nutritional Aspects 10 From Molecular Nutrition to Nutritional Systems Biology 127 Guy Vergères 10.1 Impact of Life Sciences on Molecular Nutrition Research 127 10.2 Nutrigenomics 129 10.2.1 Genomics and Nutrition Research 129 10.2.2 Transcriptomics and Nutrition Research 130 10.2.3 Proteomics and Nutrition Research 131 10.2.4 Metabolomics and Nutrition Research 132 10.3 Nutrigenetics 133 10.4 Nutri-Epigenetics 135 10.5 Nutritional Systems Biology 137 10.6 Ethics and Socio-Economics of Modern Nutrition Research 137 References 139 11 Effects of Dietary Natural Compounds on DNA Methylation Related to Cancer Chemoprevention and Anticancer Epigenetic Therapy 141 Barbara Maria Stefanska and Krystyna Fabianowska-Majewska 11.1 Introduction 141 11.2 DNA Methylation Reaction 142 11.3 Implication of the Selected Natural Compounds in DNA Methylation Regulation 144 11.3.1 ATRA, Vitamin D3 , Resveratrol, and Genistein 144 11.3.1.1 Involvement of p21 WAF1/CIP1 and Rb/E2F Pathway in Regulation of DNMT1 147 11.3.1.2 Involvement of the AP-1 Transcriptional Complex in Regulation of DNMT1 148 11.3.2 Polyphenols with a Catechol Group 149 11.4 Conclusions and Future Perspectives 151 References 152 12 Health Determinants Throughout the Life Cycle 157 Petra Rust 12.1 Introduction 157 12.2 Pre- and Postnatal Determinants 159 12.3 Determinants During Infancy and Adulthood 160 12.4 Determinants in Adults and Older People 160 12.5 Interactions Throughout the Lifecycle 161 12.6 Intergenerational Effects 161 References 162 Part V Case Studies 13 Viral Infections and Epigenetic Control Mechanisms 167 Klaus R. Huber 13.1 The Evolutionary Need for Control Mechanisms 167 13.2 Control by RNA Silencing 168 13.3 Viral Infections and Epigenetic Control Mechanisms 169 13.3.1 RNA Silencing in Plants 169 13.3.2 RNA Silencing in Fungi 170 13.3.3 RNA Silencing in Mammals 170 13.4 Epigenetics and Adaptive Immune Responses 171 References 171 14 Epigenetics Aspects in Gyneacology and Reproductive Medicine 173 Alexander Just and Johannes Huber References 178 15 Epigenetics and Tumorigenesis 179 Heidrun Karlic and Franz Varga 15.1 Introduction 179 15.2 Role of Metabolism Within the Epigenetic Network 181 15.3 Epigenetic Modification by DNA Methylation During Lifetime 183 15.4 Interaction of Genetic and Epigenetic Mechanisms in Cancer 184 15.5 DNA Methylation in Normal and Cancer Cells 185 15.6 Promoter Hypermethylation in Hematopoietic Malignancies 186 15.7 Hypermethylated Gene Promoters in Solid Cancers 187 15.8 Interaction DNA Methylation and Chromatin 188 References 190 16 Epigenetic Approaches in Oncology 195 Sabine Zöchbauer-Müller and Robert M. Mader 16.1 Introduction 195 16.2 DNA Methylation, Chromatin and Transcription 196 16.3 Methods for Detecting Methylation 197 16.4 The Paradigm of Lung Cancer 198 16.4.1 Frequently Methylated Tumor Suppressor Genes and Other Cancer-Related Genes in Lung Carcinomas 199 16.4.2 Monitoring of DNA Methylation in Blood Samples 200 16.5 Epigenetics and Therapy 200 16.6 Epigenetic Alterations Under Cytotoxic Stress 201 16.7 Therapeutic Applications of Inhibitors of DNA Methylation 202 16.8 How May Methylation Become Relevant to Clinical Applications? 203 16.9 Conclusions 204 References 205 17 Epigenetic Dysregulation in Aging and Cancer 209 Despina Komninou and John P. Richie 17.1 Introduction 210 17.2 The Cancer-Prone Metabolic Phenotype of Aging 210 17.3 Age-Related Epigenetic Silencing Via DNA Methylation 212 17.4 Inflammatory Control of Age-Related Epigenetic Regulators 214 17.5 Lessons from Anti-Aging Modalities 215 17.6 Conclusions 217 References 218 18 The Impact of Genetic and Environmental Factors in Neurodegeneration: Emerging Role of Epigenetics 225 Lucia Migliore and Fabio Coppedè 18.1 Neurodegenerative Diseases 225 18.2 The Role of Causative and Susceptibility Genes in Neurodegenerative Diseases 226 18.3 The Contribution of Environmental Factors to Neurodegenerative Diseases 231 18.4 Epigenetics, Environment and Susceptibility to Human Diseases 233 18.5 Epigenetics and Neurodegenerative Diseases 234 18.6 The Epigenetic Role of the Diet in Neurodegenerative Diseases 237 18.7 Concluding Remarks 238 References 239 19 Epigenetic Biomarkers in Neurodegenerative Disorders 245 Borut Peterlin 19.1 Introduction 245 19.2 Epigenetic Marks in Inherited Neurological and Neurodegenerative Disorders 246 19.3 Epigenetic Dysregulation in Neurodegenerative Disorders 247 19.4 Gene Candidates for Epigenetic Biomarkers 248 19.5 Conclusions 249 References 250 20 Epigenetic Mechanisms in Asthma 253 Rachel L. Miller and Julie Herbstman 20.1 Introduction 253 20.2 Epigenetic Mechanisms 255 20.3 Fetal Basis of Adult Disease 255 20.4 Fetal Basis of Asthma 256 20.5 Experimental Evidence 257 20.6 Epigenetic Mechanisms in Asthma 257 20.7 Cell-Specific Responses 259 20.8 Conclusion 259 References 260 Part VI Ways to Translate the Concept 21 Public Health Genomics – Integrating Genomics and Epigenetics into National and European Health Strategies and Policies 267 Tobias Schulte in den Bäumen and Angela Brand 21.1 Public Health and Genomics 267 21.2 The Bellagio Model of Public Health Genomics 268 21.3 The Public Health Genomics European Network 271 21.4 From Public Health Genomics to Public Health and Epigenetics/ Epigenomics 272 21.5 Health in All Policies – Translating Epigenetics/Epigenomics into Policies and Practice 272 21.6 Health in All Policies as a Guiding Concept for European Policies 273 21.7 Relative Risk and Risk Regulation – A Model for the Regulation of Epigenetic Risks? 274 21.8 Attributable Risks and Risk Regulation 275 21.9 Translating Attributable Risks into Policies 275 21.10 Limits to the Concept of Health in All Policies in Genomics and Epigenetics 277 21.11 Conclusion 278 References 278 22 Taking a First Step: Epigenetic Health and Responsibility 281 Astrid H. Gesche 22.1 Introduction 281 22.2 Responding to Epigenetic Challenges 282 22.3 Responsibility and Public Health Care Policy 283 22.4 Conclusion 284 References 285 Index 287

Autorenportrait

Alexander G Haslberger is group leader at the Department for Nutritional Sciences at the University of Vienna where he also received his academic degrees. He worked in research groups of the Sandoz Research Inst., the University of Minnesota, the WHO in Geneva and headed a group at the Fed. Ministry of Health, Vienna. He participated in the preparation of the WHO report on modern food biotechnology, the UN Millennium Ecosystem Assessment, the preparation of the OECD conference on genetic testing, Vienna 2000, the Public Health Genomic EC network, EC research projects and in WHO expert groups.