Energy Balance and Gastrointestinal Cancer (Energy Balance and Cancer, Vol. 4)

Annotation. The gastrointestinal track provides one of the distinct systems where multiple malignancies, including adenocarcinoma of the pancreas, esophagus and colon are each associated with obesity. This unique association is covered in this volume of Energy Balance and Cancer from the epidemiologic, biologic and potential etiologic viewpoint. The focus on possible dietary contribution as well as the role of exercise in prevention and therapy is presented in both animal model and patient based studies. Special focus is provided also on the role of genetic mutations and inflammatory pathways as drivers of these obesity related gastrointestinal malignancies. Overall, this volume on Energy Balance and Gastrointestinal Malignancies should be valuable to Epidemiologists, Gastroenterologists and Oncologists, as well as to students and researchers from multiple disciplines interested in understanding and disrupting the association between obesity and cancer cover 1 Front matter 2 Energy Balance and Gastrointestinal Cancer 4 Preface 6 References 7 Contents 10 Contributors 12 Obesity and Gastrointestinal Cancers Epidemiology 14 Chapter 1: Obesity and Gastrointestinal Cancers: Epidemiology 14 1 Obesity: Definitions 14 2 Obesity Rates 15 3 Gastrointestinal Cancers: Incidence Rates 16 4 Gastrointestinal Cancers: Mortality Rates 18 5 Obesity and Metabolic Syndrome 19 6 Obesity and Gastrointestinal Cancers: Epidemiological Evidence 20 6.1 Obesity and Colorectal Cancers 20 6.2 Obesity and Esophageal Cancer 25 6.3 Obesity and Gastric Cancer 26 6.4 Obesity and Gallbladder Cancer 26 6.5 Obesity and Liver Cancer 27 6.6 Obesity and Pancreatic Cancer 27 7 Obesity and Gastrointestinal Cancer Mortality: Epidemiological Evidence 28 8 Metabolic Syndrome and Gastrointestinal Cancers: Epidemiological Evidence 30 9 Conclusions 30 References 31 Genetics of Colon Cancer Susceptibility 36 Chapter 2: Genetics of Colon Cancer Susceptibility 36 1 Familial Adenomatous Polyposis 37 2 Hereditary Nonpolyposis Colon Cancer/Lynch Syndrome 38 3 MUTYH-Associated Polyposis 41 4 Familial Colorectal Cancer Type X 42 5 Hamartomatous Polyposis and Other Rare Syndromes 42 6 Genome-Wide Association Studies and Low-Penetrance Mutations 44 7 CRC Susceptibility Genes and Energy Balance 47 References 49 Dietary Modulation of Colon Cancer Effects on Intermediary Metabolism, Mucosal Cell Differentiation, and Inflammation 59 Chapter 3: Dietary Modulation of Colon Cancer: Effects on Intermediary Metabolism, Mucosal Cell Differentiation, and Inflammation 59 1 Introduction 60 2 Links of Intestinal Tumor Models to Inflammation 60 3 The Importance of Nutrients, in Particular Vitamin D and Calcium, in Human Colon Cancer 62 4 Insight on Nutrition and Intestinal Cancer from Mouse Models 64 5 Cellular and Molecular Effects of Diet and Inflammation on Intestinal Tumorigenesis 67 6 Concluding Remarks 70 References 72 The ApcMin+ Mouse Model to Study the Effects of Exercise on Gastrointestinal Malignancy 77 Chapter 4: The Apc Min/+ Mouse Model to Study the Effects of Exercise on Gastrointestinal Malignancy 77 References 85 Obesity and the Pathogenesis of Barrett’s Esophagus 88 Chapter 5: Obesity and the Pathogenesis of Barrett’s Esophagus 88 1 Introduction 88 2 Definition: Barrett’s Esophagus 89 3 GERD and BE 89 4 The Cancer Progression Model of Esophageal Adenocarcinoma 91 5 Prevalence of BE and EAC 91 6 Obesity Is the Key Modifiable Risk Factor at Each Stage of Neoplastic Progression 93 6.1 GERD, EAC, and Obesity 93 7 BE and Obesity 93 7.1 BMI and BE Meta-analysis 95 7.2 Central Obesity and BE 96 8 Central Obesity and GERD as Comodulators of BE Pathogenesis 97 8.1 Evidence for Leptin 98 8.2 Evidence for Adiponectin 98 8.3 Evidence for Free Fatty Acids 99 9 Future Directions: Physical Activity as a Modifiable Risk Factor 99 References 101 Obesity and Pancreatic Cancer 104 Chapter 6: Obesity and Pancreatic Cancer 104 1 Pancreatic Cancer 104 2 Obesity and Risk of Pancreatic Cancer 105 2.1 Body Mass Index 105 2.2 Central Adiposity 107 2.3 Physical Activity 108 3 Obesity and Age of Onset and Survival of Pancreatic Cancer 109 3.1 Age of Onset 109 3.2 Survival 109 3.3 Mortality 109 4 Mechanism of Obesity-Related Pancreatic Cancer 110 4.1 Adipokines 110 4.2 Insulin Resistance 111 4.3 Inflammation 112 4.4 Genetic Susceptibility 114 5 Conclusion 114 References 115 Obesity, Insulin Resistance Pathway Factors, and Colon Cancer 121 Chapter 7: Obesity, Insulin Resistance Pathway Factors, and Colon Cancer 121 1 Introduction 121 2 Energy Imbalance and Colon Cancer 122 2.1 Excess Energy Consumption 123 2.2 Physical Inactivity 124 2.3 Obesity 124 2.4 Adult Weight Gain 125 2.5 Diabetes Mellitus 126 2.6 Metabolic Syndrome 126 3 Biomarkers: Insulin Resistance, Insulin-Like Growth Factors, Adipokines and Inflammatory Cytokines 127 3.1 Insulin Resistance 127 3.2 Insulin-Like Growth Factors 128 3.3 Adipokines and Inflammatory Cytokines 129 4 Possible Mechanisms Linking Obesity, Insulin Resistance to Colon Cancer 129 5 Future Directions 131 5.1 Emerging New Risk Factors for Colon Cancer 131 5.1.1 Gut Microbiota 131 5.1.2 Sleep Disturbance 132 5.2 Chemoprevention of Colon Cancer Targeting Insulin Resistance Pathways 132 References 133 Ras Raf and Their Influence in Glycolysis in Colon Cancer 140 Chapter 8: Ras/Raf and Their Influence in Glycolysis in Colon Cancer 140 1 Introduction 140 2 The Ras/Raf Pathway 141 3 Activation of Ras/Raf Signaling During Colorectal Tumorigenesis 142 4 Upregulation of GLUT1 in Cells with Constitutive Ras/Raf Signaling 143 5 Clinical Implications 145 6 Conclusion 146 References 146 Energy Balance and Other Modifiable Host Factors on Colorectal Cancer Prognosis 149 Chapter 9: Energy Balance and Other Modifiable Host Factors on Colorectal Cancer Prognosis 149 1 Colorectal Cancer Statistics 149 2 Colorectal Cancer Staging and Standard Treatments 150 3 Risk Factors for Colorectal Cancer: Energy Balance 150 4 Risk Factors Influencing Outcomes 151 5 Obesity and Colorectal Cancer Prognosis 152 6 Physical Activity and Colorectal Cancer Prognosis 154 7 Diet and Colon Cancer Outcomes 156 8 Potential Mechanisms of Energy Balance Factors and Outcomes in Colorectal Cancer Survivors 158 9 Conclusions 159 References 159 Cyclooxygenase-2 and Chronic Inflammation Drivers of Colorectal Tumorigenesis 165 Chapter 10: Cyclooxygenase-2 and Chronic Inflammation: Drivers of Colorectal Tumorigenesis 165 Abstract 165 1 Historical Perspective 165 2 The Inflammatory Response in Gastrointestinal Tissue 166 3 Chronic Inflammation, COX-2 and Colorectal Neoplasia 168 4 The Role of COX-2 in Obesity and Metabolic Syndrome 171 5 Protumorigenic Effects of PGE 2 171 6 Mechanistic Insights from the Intestinal Inflammatory Response 173 7 Pharmacological Agents Inhibiting Tissue Inflammation 173 8 COX-2-Dependent Effects of NSAIDs in Colorectal Neoplasia 175 9 Activity of Anti-inflammatory Drugs Against Colorectal Neoplasia 177 10 Prevention Clinical Trials 178 11 Efficacy Against Established Colon Cancers 179 12 Clinical Trials in Cancer Treatment 180 13 Summary and Future Directions 181 References 182 Back matter 191 Index 191 Front Matter....Pages i-xii Obesity and Gastrointestinal Cancers: Epidemiology....Pages 1-22 Genetics of Colon Cancer Susceptibility....Pages 23-45 Dietary Modulation of Colon Cancer: Effects on Intermediary Metabolism, Mucosal Cell Differentiation, and Inflammation....Pages 47-64 The Apc Min/+ Mouse Model to Study the Effects of Exercise on Gastrointestinal Malignancy....Pages 65-75 Obesity and the Pathogenesis of Barrett’s Esophagus....Pages 77-92 Obesity and Pancreatic Cancer....Pages 93-109 Obesity, Insulin Resistance Pathway Factors, and Colon Cancer....Pages 111-129 Ras/Raf and Their Influence in Glycolysis in Colon Cancer....Pages 131-139 Energy Balance and Other Modifiable Host Factors on Colorectal Cancer Prognosis....Pages 141-156 Cyclooxygenase-2 and Chronic Inflammation: Drivers of Colorectal Tumorigenesis....Pages 157-182 Back Matter....Pages 183-184