Environmental Factors, Genes, and the Development of Human Cancers (eBook)

Preface 4
Acknowledgments 6
Contents 7
Contributors 9
Part I General Principles 12
1 Introduction 13
1.1 Environment and Cancer 14
1.2 Interactions Between Genes and Environment, and Risk of Cancer 15
1.3 Biological and Statistical Interaction 17
1.4 Benefits of Considering the Environment in Genetic Association Studies 18
References 18
2 Gene--Environment Interactions, Phenotypic Changes,and Human Health 20
2.1 History of the Relationship Between Genes, Environment, and Human Disease 21
2.2 Health Disparities and Genetics 22
2.3 Studying GeneEnvironment Interactions and Disease 23
2.4 The Environment, Genes, and Cancer 26
2.4.1 Bladder Cancer 27
2.4.2 Breast Cancer 35
2.4.3 Colorectal Cancer 37
2.4.4 Esophageal Cancer 38
2.4.5 Leukemia 39
2.4.6 Liver Cancer 42
2.4.7 Lung Cancer 43
2.4.8 Melanoma 45
2.4.9 Occupational-Related Cancer 47
2.4.10 Pancreatic Cancer 48
2.4.11 Prostate Cancer 49
2.5 Summary 51
References 51
3 Statistics for Testing GeneEnvironment Interaction 61
3.1 Introduction 61
3.2 Measure of Interaction Between Gene and Binary Environment 65
3.2.1 Traditional Measure of Gene--Environment Interaction 65
3.2.1.1 The Measure of Gene--Environment Interaction for the Cohort Study Design 65
3.2.1.2 The Measure of Gene--Environment Interaction for the Case-Control Study Design 67
3.2.2 Disequilibrium Measure of Gene--Environment Interaction 69
3.2.3 Information Measure of Gene--Environment Interaction 70
3.3 Measure of Interaction Between Gene and Continuous Environment 72
3.3.1 Multiplicative Measure of Interaction Between Gene and Continuous Environment 73
3.3.2 Disequilibrium Measure of Interaction Between Gene and Continuous Environment 74
3.3.3 Mutual Information Measure of Interaction Between Gene and Continuous Environment 74
3.4 Statistics for Testing Interaction Between Gene and Environment 76
3.4.1 Relative Risk and Odds-Ratio-Based Statistics for Testing Interaction Between Gene and Discrete Environment 76
3.4.2 Disequilibrium-Based Statistics for Testing Interaction Between Gene and Discrete Environment 81
3.4.3 Information-Based Statistics for Testing Interaction Between Gene and Discrete Environment 82
3.4.4 Multiplicative Measure-Based Statistics for Testing Interaction Between Gene and Continuous Environment 86
3.4.5 Information Measure-Based Statistics for Testing Interaction Between Gene and Continuous Environment 87
3.5 Canonical Correlation for Testing Interaction Between a Gene (Multiple SNPs) and Environment 88
3.6 GeneEnvironment Interaction in Cancers 91
3.7 Real Examples for Application of Different Measures of Gene and Environment Interactions 93
3.8 Conclusion 96
References 100
4 Clustering Studies for Identifying the Role of Environmental Factors in Aetiology of Human Cancers 104
4.1 Introduction 104
4.2 Post-hoc Cluster Investigations 106
4.3 Systematic Studies of Global Space-Time Clustering 108
4.4 Systematic Studies of Global Spatial Clustering 113
4.5 Systematic Studies of Global Temporal Clustering 115
4.6 Systematic Studies to Identify Individual Clusters 115
4.7 Conclusions 116
References 116
5 Discovering Gene-Gene and Gene-Environment Causal Interactions Using Bioinformatics Approaches 122
5.1 Introduction 123
5.2 Background 126
5.2.1 Medicine and Statistics 126
5.2.2 Molecular Biology 127
5.2.3 Artificial Intelligence 128
5.3 Gene-Gene Causal Interaction Model 129
5.3.1 Boolean Networks 130
5.3.2 Continuous Models 131
5.3.3 Bayesian Networks 132
5.3.4 Mixture Models and Other Models 134
5.4 Gene-Environment Causal Interaction Models 134
5.4.1 Modeling Experiments in Bayesian Networks 135
5.4.1.1 A General Bayesian Analysis 135
5.4.2 Gene--Environment Causal Interaction Models Through Modeling Manipulation 137
5.4.2.1 Evaluating Causal Bayesian Networks 138
5.5 Conclusion and Future Direction 139
References 141
6 Gene Environment Interactions and Vascular Lesions 146
6.1 Introduction 146
6.2 Angiogenic Lesion Development 147
6.3 Environment and Vascular Lesions 148
6.4 Redox Signaling and Vascular Lesions 149
6.5 Angiogenic Genes 152
6.6 Genetic Susceptibility to Vascular Lesions 152
6.7 GeneEnvironment Interactions and Vascular Lesion Development 153
6.8 Summary 154
References 155
7 Epigenetic Changes in Cancer: Role of Environment 160
7.1 Introduction 160
7.2 Epigenetic Changes Play an Important Role in the Development of Cancer 162
7.3 DNA Methylation Changes in Cancer 164
7.4 Role of Histone Modifications in Cancer 166
7.5 Epigenetic Changes Induced by Environmental Factors in Human Cancer 167
7.6 Examples of Environmental Epimutagens 170
7.7 Susceptibility to Epigenetic Changes and Cancer 177
7.8 Concluding Remarks and Perspectives 183
References 186
8 Approaches to Identify Environmental and Epigenomic Components or Covariates of Cancer and Disease Susceptibility 204
8.1 Introduction 205
8.2 Approaches to Identify Genetic Variance 206
8.2.1 Candidate Gene 207
8.2.2 Copy Number Variations (CNVs) 209
8.2.3 Single Nucleotide Polymorphism (SNP) 209
8.2.4 Haplotype Mapping 210
8.2.5 Genome Wide Association Screen 211
8.3 Data Collection and Public Databases 212
8.4 Environmental Epigenomics and Disease Susceptibility 213
8.5 Analysis of GxE Interactions 215
8.5.1 Qualitative Models 216
8.5.2 Statistical Models 217
8.5.2.1 Biological Plausibility 217
8.6 Study Designs for Association Analyses 218
8.6.1 Family-Based Study 218
8.6.2 Unrelated Individuals 218
8.6.2.1 Retrospective Design 219
8.6.2.2 Prospective Design 219
8.6.2.3 Case-Only Designs 221
8.7 Critical Parameters 221
8.7.1 Sample Size 221
8.7.2 Complex Mixture of Covariates 222
8.7.3 Coordination in Data Collection and Their Meta-analysis 222
8.8 Summary 223
References 224
Online Resources 226
Part II Environment and Specific Types of Cancer 227
9 GeneEnvironment Interaction and Susceptibility to Pediatric Brain Tumors 228
9.1 Introduction 229
9.2 Environmental Epidemiology of Pediatric Brain Tumors 231
9.2.1 Links Between the Environment and Traditional Epidemiology and Risk Factors 231
9.2.2 Epidemiologic Research on Specific Environmental Exposures and pBT 232
9.3 Origin and Neurobiology of Pediatric Brain Tumors 234
9.3.1 Cellular Origins of pBTs 235
9.3.2 Disruption of Developmental Pathways, ''Tumor Precursor Cells'', and pBTs 236
9.4 Genetic and Epigenetic Alterations in Pediatric Brain Tumors 238
9.5 Environment, Mitochondrial-Nuclear Interactions, and Development of Pediatric Brain Tumors 239
9.5.1 Effects of Early Life Exposures on Mitochondria and the Pediatric Brain 240
9.5.2 Experimental Evidence Linking Early Life Exposures to Mitochondrial Dysfunction and pBT Development 242
9.5.3 Mitochondrial ROS, Electron Transport Chain Defects, and Pediatric Susceptibility 243
9.5.4 Evidence of Mitochondrial-Nuclear Interactions and Mitochondrial Dysfunction in pBTs 244
9.6 Population Studies on GeneEnvironment Interactions in Pediatric Brain Tumors 248
9.7 Conclusions 250
References 251
10 Genetic Polymorphisms Predisposing Individuals to Breast Cancer Via GeneEnvironment Interaction 258
10.1 Introduction 259
10.2 Obesity 259
10.3 Hormonal Factors 261
10.4 Dietary Factors 264
10.5 Alcohol 264
10.6 Folate 266
10.7 Fruits, Vegetables, and Antioxidant Vitamins 267
10.8 Iron Overload 269
10.9 Meat and Meat Mutagens 269
10.10 Other Environmental Factors 270
10.10.1 Circadian Disruption 270
10.11 Conclusions 270
References 271
11 Environment, Genetic Immunology and Childhood Cancer 282
11.1 Childhood Cancer Epidemiology, Genes and Environment 282
11.1.1 Study Design Issues 283
11.1.2 Environment and Childhood Cancer 285
11.1.3 Gene and Environment Interaction, and Childhood Cancer 288
11.2 Genetic Immunology and Childhood Cancer 289
11.2.1 Infections and Childhood Cancer 290
11.2.2 Autoimmune Diseases and Childhood Cancer 292
11.2.3 Atopic Diseases and Childhood Cancer 293
11.2.4 HLA Associations and Childhood Cancer 294
11.2.5 Iron and Immune Surveillance 295
11.2.6 Sex Effect in Predisposition to Childhood Cancer 295
11.3 Future Prospects 297
References 297
Internet Links 307
12 Exposure to Environmental Mutagens: APC and Colorectal Carcinogenesis 308
12.1 Introduction 309
12.2 Features of Colorectal Carcinogenesis 310
12.3 Genes and Individual Susceptibility to Colorectal Cancer 311
12.4 Environmental Factors Affecting DNA Repair and Colorectal Cancer Susceptibility 312
12.5 Dietary Components 313
12.6 Alcohol 315
12.7 Cigarette Smoking 316
12.8 Adenomatous Polyposis Coli (APC) in Base Excision Repair and Colorectal Carcinogenesis 317
12.9 Polymorphism in APC Gene and Risk of Colorectal Cancer 323
12.10 Conclusion 325
References 326
13 Gene-Environmental Interactions and Susceptibility to Liver Cancer 335
13.1 Gene-Environmental Interactions and Susceptibility to Liver Cancer 336
13.1.1 Biological Agents in the Environment and Their Interactions with Genes That Predispose to Liver Cancer (Hepatocellular Carcinoma) 336
13.1.2 Chemical Agents in the Environment and Their Interactions with Genes That Predispose to Liver Cancer 342
13.1.3 Family History and the Risk of Liver Cancer 354
13.1.4 Summary of the Diverse Molecular Mechanisms of Hepatocarcinogenesis 355
13.1.5 Biomarkers of Susceptibility to Liver Cancer 357
References 359
14 Genetic Epidemiology of Mismatch Repair Deficiency in Ovarian Cancer 370
14.1 Introduction 370
14.2 Molecular Basis of Mismatch Repair Defects 371
14.3 Clinical Characteristics of Mismatch Repair Defects 373
14.4 MSI Status and Ovarian Cancer 375
14.5 MMR Protein Expression in Ovarian Cancers 377
14.6 Histology of HNPCC-Associated and/or MSI-H Ovarian Tumors 380
14.7 MLH1 Promoter Hypermethylation and Somatic Mutations Leading to MSI-H Tumors 382
14.8 Epidemiologic Risk Factors and Their Relationship to Microsatellite Instability 386
14.9 Survival and Treatment Implications Associated with Ovarian Cancers with MMR Deficiency 388
14.10 Conclusion and Future Directions 390
References 390
Part III Case Studies 402
15 Betel Nut and Susceptibility to Cancer 403
15.1 Introduction 403
15.1.1 Constituents of Betel Nut and Its Active Principles 405
15.1.2 General Effects of Betel Nut Consumption 407
15.1.3 Link Between Betel Nut and Carcinogenesis 408
15.1.3.1 Induction of Pre-cancerous Lesions by Betel Nut 409
15.1.3.2 Betel Nut and Betel Nut Extracts in Carcinogenesis 410
15.1.3.3 Betel Nut Alkaloids in Carcinogenesis 412
15.1.4 Betel Nut and Tumor Suppressor Genes TP53, BRCA1 and BRCA2 414
15.1.5 Betel Nut Polyphenol and Tannins in Carcinogenesis 419
15.1.6 Betel Nut and Human Genetic Susceptibility to Oral Cancer 420
15.1.7 Possible Mechanism of Betel Nut Induced Carcinogenesis 420
References 425
16 Birth Weight and Cancer Associations 431
16.1 Importance of Birth Weight 431
16.2 Determinants of Birth Weight 432
16.3 Birth Weight and Cancer Connection 435
16.4 Possible Mechanisms of Birth Weight Association in Childhood Cancer 436
16.5 Obesity and Cancer 439
References 439
17 Iron Excess and Cancer 447
17.1 Introduction 447
17.2 Iron and Its Pro-Carcinogenic Effect 449
17.3 Environmental Sources of Iron 451
17.3.1 Red Meat 451
17.3.2 Home Brewed Beer in Africa 452
17.3.3 Other Food Stuff 452
17.3.4 Soil 453
17.3.5 Occupational Exposures 453
17.4 Genetic Control of Iron Homeostasis 454
17.5 Population at Risk for Iron Excess 456
17.6 Gene and Environment Interactions in Iron Excess and Cancer Connection 457
17.7 Biomarkers for Iron Intake and Body Iron Levels 459
17.8 Possible Contribution of Iron to Epidemiologic Associations with Cancer 460
17.9 Conclusions 464
References 465
Glossary 478
Biostatistic, Epidemiologic and Genetic Terms Used in Genetic and Environmental Epidemiology of Cancer 478
Index 499