Epigenetics and Human Health: Linking Hereditary, Environmental and Nutritional Aspects

Epigenetics and Human Health......Page 5
Contents......Page 9
Preface......Page 17
List of Contributors......Page 19
Part I: General Introduction......Page 25
1: The Research Program in Epigenetics: The Birth of a New Paradigm......Page 27
References......Page 29
2.1 Introduction......Page 31
2.3 Current Nutrition Related Health Problems......Page 32
References......Page 33
3: Epigenetics: Comments from an Ecologist......Page 35
References......Page 36
4.1 Hereditary Dispositions......Page 37
4.2 The Epigenome......Page 38
4.3.1 Methylation......Page 39
4.3.2 Histone Modifications......Page 42
4.4.1 Nutritional and Environmental Effects in Early Life Conditions......Page 44
4.5 Dietary Effects......Page 46
4.5.2 Nutrition and Aging......Page 50
4.6 Inheritance and Evolutionary Aspects......Page 52
4.7 Conclusion......Page 53
References......Page 54
Part II: Hereditary Aspects......Page 59
5.1.1 Definition and Goals of Genetic Epidemiology......Page 61
5.1.3 The Human Genome......Page 62
5.1.4 Meta-Analysis in Genetic Epidemiology......Page 63
5.1.5 Human Genome Epidemiology Network......Page 64
5.2.1 Gene and Function......Page 65
5.2.3 Gene–Environment Interaction......Page 67
5.3 Meta-Analyses of Methylenetetrahydrofolate Reductase C677T and A 1298C Polymorphisms and Cancer......Page 68
References......Page 71
6.1 Background......Page 75
6.1.1 What Purpose Do Different Biobank Formats Serve?......Page 76
6.1.2 Why Do We Need Networks of Biobanks?......Page 77
6.2 The Investigation of Gene–Environment Interactions as a Challenge for Biobanks......Page 79
6.2.2 Why Are Biobanks Needed in This Context and What Challenges Do They Have to Face?......Page 82
References......Page 84
7: Case Studies on Epigenetic Inheritance......Page 87
7.1 Introduction......Page 88
7.2.1 On the Study of Epigenetic Inheritance......Page 89
7.2.2 The Ideal Study Design......Page 90
7.2.3 The Överkalix Cohorts of 1890, 1905 and 1920......Page 91
7.2.5 The Proband’s Childhood......Page 92
7.2.8 Growth Velocity......Page 93
7.3.1 The Social Context......Page 94
7.3.3 Longevity and Paternal Ancestors’ Nutrition......Page 95
7.3.4 The Influence of Nutrition During the Slow Growth Period on Cardiovascular and Diabetes Mortality......Page 96
7.3.5 Is Human Epigenetic Inheritance Mediated by the Sex Chromosomes?......Page 97
7.3.6 Epigenetic Inheritance, Early Life Circumstances and Longevity......Page 99
7.3.7.2 Chromosomal Transmission of Nutritionally Induced Epigenetic Modifications......Page 100
7.4 Epigenetic Inheritance......Page 101
7.4.1 Fetal Programming and Epigenetic Inheritance......Page 102
7.5 Future Directions......Page 104
7.6 Conclusions......Page 105
References......Page 107
Part III: Environmental and Toxicological Aspects......Page 111
8: Genotoxic, Non-Genotoxic and Epigenetic Mechanisms in Chemical Hepatocarcinogenesis: Implications for Safety Evaluation......Page 113
8.1 Introduction......Page 114
8.2.1 Tumor Initiation......Page 115
8.2.2 Tumor Promotion......Page 116
8.2.4 Cellular and Molecular Mechanisms of Tumor Initiation and Promotion......Page 117
8.2.5 Epigenetic Effects of Genotoxic and Non-Genotoxic Hepatocarcinogens......Page 120
8.3 Concluding Remarks......Page 121
References......Page 123
9.1 Introduction......Page 129
9.2 Genotoxic Carcinogens in Human Foods......Page 130
9.2.2 Nitrosamines......Page 131
9.2.3 Heterocyclic Aromatic Amines (HAAs) and Other Thermal Degradation Products......Page 132
9.2.5 Food Additives and Carcinogens in Plant-Derived Foods......Page 133
9.3 Contribution of Genotoxic Dietary Carcinogens to Human Cancer Risks......Page 135
9.4 Protective Effects of Dietary Components Towards DNA-Reactive Carcinogens......Page 136
9.5 Gene Polymorphisms Affecting the Metabolism of Genotoxic Carcinogens......Page 138
References......Page 142
Part IV: Nutritional Aspects......Page 149
10.1 Impact of Life Sciences on Molecular Nutrition Research......Page 151
10.2.1 Genomics and Nutrition Research......Page 153
10.2.2 Transcriptomics and Nutrition Research......Page 154
10.2.3 Proteomics and Nutrition Research......Page 155
10.2.4 Metabolomics and Nutrition Research......Page 156
10.3 Nutrigenetics......Page 157
10.4 Nutri-Epigenetics......Page 159
10.6 Ethics and Socio-Economics of Modern Nutrition Research......Page 161
References......Page 163
11.1 Introduction......Page 165
11.2 DNA Methylation Reaction......Page 166
11.3.1 ATRA, Vitamin D3, Resveratrol, and Genistein......Page 168
11.3.1.1 Involvement of p21WAF1/CIP1 and Rb/E2F Pathway in Regulation of DNMT1......Page 171
11.3.1.2 Involvement of the AP-1 Transcriptional Complex in Regulation of DNMT1......Page 172
11.3.2 Polyphenols with a Catechol Group......Page 173
11.4 Conclusions and Future Perspectives......Page 175
References......Page 176
12.1 Introduction......Page 181
12.2 Pre-and Postnatal Determinants......Page 183
12.4 Determinants in Adults and Older People......Page 184
12.6 Intergenerational Effects......Page 185
References......Page 186
Part V: Case Studies......Page 189
13.1 The Evolutionary Need for Control Mechanisms......Page 191
13.2 Control by RNA Silencing......Page 192
13.3.1 RNA Silencing in Plants......Page 193
13.3.3 RNA Silencing in Mammals......Page 194
References......Page 195
14: Epigenetics Aspects in Gyneacology and Reproductive Medicine......Page 197
References......Page 202
15.1 Introduction......Page 203
15.2 Role of Metabolism Within the Epigenetic Network......Page 205
15.3 Epigenetic Modification by DNA Methylation During Lifetime......Page 207
15.4 Interaction of Genetic and Epigenetic Mechanisms in Cancer......Page 208
15.5 DNA Methylation in Normal and Cancer Cells......Page 209
15.6 Promoter Hypermethylation in Hematopoietic Malignancies......Page 210
15.7 Hypermethylated Gene Promoters in Solid Cancers......Page 211
15.8 Interaction DNA Methylation and Chromatin......Page 212
References......Page 214
16.1 Introduction......Page 219
16.2 DNA Methylation, Chromatin and Transcription......Page 220
16.3 Methods for Detecting Methylation......Page 221
16.4 The Paradigm of Lung Cancer......Page 222
16.4.1 Frequently Methylated Tumor Suppressor Genes and Other Cancer-Related Genes in Lung Carcinomas......Page 223
16.5 Epigenetics and Therapy......Page 224
16.6 Epigenetic Alterations Under Cytotoxic Stress......Page 225
16.7 Therapeutic Applications of Inhibitors of DNA Methylation......Page 226
16.8 How May Methylation Become Relevant to Clinical Applications?......Page 227
16.9 Conclusions......Page 228
References......Page 229
17: Epigenetic Dysregulation in Aging and Cancer......Page 233
17.2 The Cancer-Prone Metabolic Phenotype of Aging......Page 234
17.3 Age-Related Epigenetic Silencing Via DNA Methylation......Page 236
17.4 Inflammatory Control of Age-Related Epigenetic Regulators......Page 238
17.5 Lessons from Anti-Aging Modalities......Page 239
17.6 Conclusions......Page 241
References......Page 242
18.1 Neurodegenerative Diseases......Page 249
18.2 The Role of Causative and Susceptibility Genes in Neurodegenerative Diseases......Page 250
18.3 The Contribution of Environmental Factors to Neurodegenerative Diseases......Page 255
18.4 Epigenetics, Environment and Susceptibility to Human Diseases......Page 257
18.5 Epigenetics and Neurodegenerative Diseases......Page 258
18.6 The Epigenetic Role of the Diet in Neurodegenerative Diseases......Page 261
18.7 Concluding Remarks......Page 262
References......Page 263
19.1 Introduction......Page 269
19.2 Epigenetic Marks in Inherited Neurological and Neurodegenerative Disorders......Page 270
19.3 Epigenetic Dysregulation in Neurodegenerative Disorders......Page 271
19.4 Gene Candidates for Epigenetic Biomarkers......Page 272
19.5 Conclusions......Page 273
References......Page 274
20.1 Introduction......Page 277
20.3 Fetal Basis of Adult Disease......Page 279
20.4 Fetal Basis of Asthma......Page 280
20.6 Epigenetic Mechanisms in Asthma......Page 281
20.8 Conclusion......Page 283
References......Page 284
Part VI: Ways to Translate the Concept......Page 289
21.1 Public Health and Genomics......Page 291
21.2 The Bellagio Model of Public Health Genomics......Page 292
21.3 The Public Health Genomics European Network......Page 295
21.5 Health in All Policies – Translating Epigenetics/Epigenomics into Policies and Practice......Page 296
21.6 Health in All Policies as a Guiding Concept for European Policies......Page 297
21.7 Relative Risk and Risk Regulation – A Model for the Regulation of Epigenetic Risks?......Page 298
21.9 Translating Attributable Risks into Policies......Page 299
21.10 Limits to the Concept of Health in All Policies in Genomics and Epigenetics......Page 301
References......Page 302
22.1 Introduction......Page 305
22.2 Responding to Epigenetic Challenges......Page 306
22.3 Responsibility and Public Health Care Policy......Page 307
22.4 Conclusion......Page 308
References......Page 309
Index......Page 311