Acute-phase response, cytokine mediation in cachexia 157, 158 ß 2 -Adrenergic agonist, effects on rat tumor models 264 Alcohol breast cancer studies 107, 108, 111, 112, 116 ß-carotene interactions 53 lung cancer studies 30 prostate cancer studies 60 Alcohol dehydrogenase, alleles in human cancer 107, 116 Anabolic competence, paradigm for nutritional intervention 197, 198 Angiogenesis, dietary modulation 12, 20 Animal models, nutrition in cancer studies dietary approaches amino acids 176 178, 181 chows 174 composition of diet 174, 175 energy intake 174, 175, 181 fatty acids 178, 181, 182 fiber 181 restricted diets 175 route of feeding 174, 178, 179 supplemented diets 175 177 extrapolation to humans advantages of diverse models 171, 172 diversity of metabolic abnormalities 172, 173 protein metabolism regulators 172 174 insulin studies 180 182 selection factors 167 transgenic mouse 13, 14 treated, tumor-bearing models chemotherapy 169, 170, 181 surgery 170, 171, 182 untreated tumor models animal carcinogenesis models 168 human tumor cells 168 transplantable tumors 168 rats, tumor weight and anorexia 168, 169 Anorexia cancer cachexia 148, 149 malnutrition in cancer 226, 239 AP-1, lung levels with ß-carotene supplementation in animals 47, 48 Apoptosis Bcl-2 role 14 dietary modulation 10 Arginine clinical trials of immunonutrition 260, 261 nitric oxide effects 260 pediatric cancer patient supplementation 281 rationale for supplementation in cancer patients 260, 273 surgical cancer patient supplementation 246 Benzo(a)pyrene diol epoxide, scavenging by nutrients 6 Benzoyl peroxide, tumor promotion mechanisms 8, 9 Biomarkers, cancer trials 285 291 Bone marrow transplant, see Hematopoietic stem cell transplant 293
Bradford Hill criteria, establishing causality 287, 288 Breast cancer breast feeding effects on maternal risk 115 dietary effects adolescence 105 alcohol 107, 108, 111, 112, 116 ß-carotene 109, 110 childhood 105, 112 fat intake 106 fiber 111 folate 110, 116 fruits and vegetables 108, 109, 111, 112 infancy 104, 105, 115, 116 soy protein 116 vitamin A 109 vitamin C 110 vitamin E 110 epidemiology 103, 104 heredity 115 immigration studies 103, 104 premenopausal women studies 131, 132 sex hormone-binding globulin deficiency 120 Breast feeding infant diet effects on future breast cancer development 104, 105, 115 lactation effects on breast cancer development 115 Cachexia asthenia 147, 155 body composition changes 135, 141 contributing factors with surgery 239, 240 cytokines acute-phase response mediation 157, 158 food intake and malnutrition role 148, 149 hypermetabolism role of tumor necrosis factor 151 153 insulin resistance role 158, 159 lipid metabolism role 153, 154, 163 muscle wasting role 155 157 overview 137, 147, 148, 159, 160 protective cytokines 160 therapeutic targeting 161, 163, 164 weight loss induction ciliary neurotropic factor 151 interferon-á 150 interleukin-6150 leukemia-inhibitory factor 150 tumor necrosis factor 149 151, 160, 161 insulin effects in animal models 180 182 isolation of non-cytokine mediators 159 medroxyprogesterone acetate treatment 141 mortality in cancer 135, 147, 188 palliative therapy 164, 165 pediatric cancer patients consequences 276 incidence 275, 282, 284 pathogenesis 276 pharmacotherapy 281, 282, 284 risk factors 278 pentoxyphyllin therapy 163 skeletal muscle loss eicosapentaenoic acid inhibition and therapy 140 142, 144, 145 overview of mechanisms 136 proteolysis-inducing factor assay 144 evidence for muscle catabolism 136, 137 glycosylation 138, 139 isolation 137, 138 lipid modulation 139, 140 mechanism of action 139 receptor 146 regulation 144 tumor specificity 144 proteolytic pathways 139 Calcium colorectal cancer studies 76, 77 prostate cancer studies 59, 60 Caloric restriction confounding factor in animal nutrition studies 20 cycling effects 20 historical perspective of cancer studies 21 immune surveillance of malignant cell enhancement 11 lifespan effects 20, 21 mechanisms of carcinogenesis inhibition 18, 19 protein kinase C effects 10 294
Cancer cachexia, see Cachexia Cancer registry, data in nutritional epidemiology 117, 118 Carcinoembryonic antigen, marker in cancer trials 285 -Carotene, lung cancer studies 27, 28 ß-Carotene alcohol interactions 53 breast cancer studies 109, 110 colorectal cancer studies 78 80 lung cancer studies high-dose supplementation effects in smokers 42, 43, 45 49, 51 intervention studies 41, 42 mechanisms of prevention 41 oxidation products and carcinogenesis 43, 45 prospective cohort studies 24, 27, 28 vitamin C as reducing agent 50 52 vitamin E as reducing agent 50 52 metabolism in smokers 42, 43, 45, 48, 49, 54 prostate cancer studies 57, 58, 64, 65 Chemotherapy classification of agents alkylating agents 185, 186 antimetabolites 185, 186 examples 186, 187 hormones and antagonists 187 miscellaneous agents 187 natural products 185 187 historical perspective 183, 184 mechanisms in cancer 184, 185, 187 nutritional oncology anabolic competence as paradigm for nutritional intervention 197, 198 attitudes of oncologists 203, 204 bidirectional interplay of nutrition and chemotherapy 195 197 gut translocation of bacteria 191, 192 historical perspective 188, 189 hormonal factors 204, 205 immune response 190 192 parenteral nutrition 189, 190, 202, 203 protein requirements 205 standardized nutritional assessment 192 194 supplements voluntarily taken by cancer patients 202 weight loss grading 192, 193 survival outcome 188, 189 withholding of nutrition 204 pediatric cancer patients 283 treated, tumor-bearing animal models 169, 170, 181 Children, see Pediatric cancer Ciliary neurotropic factor, cachexia role, see Cachexia CNERNA-CNRS-INRA, findings on diet and cancer 119 Coffee, colorectal cancer studies 81 Colorectal cancer dietary effects calcium 76, 77 ß-carotene 78 80 coffee 81 dairy products 77 familial cancers 85, 86 fat intake fat type effects 69 meat types, preparation, and processing 68 70 mechanisms 67, 68 fiber mechanisms of protection 70 prospects for studies 72 sex differences 85 types of fiber 70, 71 folate DNA integrity maintenance 92, 93 DNA methylation in mechanism 80, 90 92, 99, 100 DNA repair in mechanism 93, 94 epidemiologic studies 80 methylenetetrahydrofolate reductase polymorphisms 94 96 RNA methylation in mechanism 92 fruits and vegetables animal studies 88 anticarcinogenic agents 72, 73 epidemiologic studies 72 74, 87 intervention trials 88 homocysteine 101 prospects for research 81, 82 295
selenium 79 sucrose 74, 75 tea 81 vitamin B 6 100, 101 vitamin C 78, 79 vitamin D 77 vitamin E 78 80 epidemiology 67 exercise effects 86 markers 287 Committee on Medical Aspects of Food and Nutrition Policy, findings on diet and cancer 119 Cori cycle, activation in cachexia 151 Cyclooxygenase inflammation role 10, 11 inhibition 11, 145 Cytochromes P450 carcinogen activation 3, 4 ß-carotene metabolism in smokers 42, 43, 45, 48, 49, 54 Cytokines, see specific cytokines Dairy products colorectal cancer studies 77 prostate cancer studies 57 DNA methylation, folate inhibition in colon cancer 80, 90 92, 99, 100 DNA repair dietary modulation 6 folate role in colon cancer 93, 94 Eicosapentaenoic acid, muscle catabolism inhibition in cachexia 140 142, 144, 145 Enteral nutrition head and neck radiotherapy patients body weight 227 effects with surgery and/or chemotherapy 230, 231 fat reserves 227, 229 lean body mass 227, 236 markers for metabolic changes 229 outpatients 232, 234, 235 parenteral nutrition and complications 234 percutaneous endoscopic gastrostomy 227, 229 232, 234 237 quality of life 229, 230, 234, 237 study design 227 hematopoietic stem cell transplant patients children 218 complications 217 costs 217, 219 total parenteral nutrition 217 219 transition to oral diet 217, 218 tube placement 222, 223 pediatric cancer patients 277, 279 surgical cancer patients 243 245, 253 European Prospective Investigation into Cancer and Nutrition aims 121, 122, 127 collaborating centers 121, 127 129 field work and subject recruitment 125, 126, 131 follow-up 126, 132 funding 131 sample storage 123, 125, 132, 133 study protocol 122, 123, 125, 132 Fat intake breast cancer studies 106 colorectal cancer studies fat type effects 69 meat types, preparation, and processing 68 70 mechanisms 67, 68 lung cancer studies 29, 30 prostate cancer studies 57, 63, 64 -Fetoprotein, marker in cancer trials 285 Fiber breast cancer studies 111 colorectal cancer studies mechanisms of protection 70 prospects for studies 72 sex differences 85 types of fiber 70, 71 Flavonols, lung cancer studies 28, 29 Folate breast cancer studies 110, 116 colorectal cancer studies DNA integrity maintenance 92, 93 DNA methylation in mechanism 80, 90 92, 99, 100 DNA repair in mechanism 93, 94 epidemiologic studies 80 methylenetetrahydrofolate reductase polymorphisms 94 96 RNA methylation in mechanism 92 lung cancer studies 28 nucleic acid metabolism role 89, 90 tissue distribution 87, 88, 101 296
Fruits and vegetables breast cancer studies 108, 109, 111, 112 colorectal cancer studies animal studies 88 anticarcinogenic agents 72, 73 epidemiologic studies 72 74, 87 intervention trials 88 lung cancer studies 24, 25, 27 29, 33, 35, 36, 40 prostate cancer studies 57, 58 Glutamine hematopoietic stem cell transplant patient treatment absorption 223 clinical trials 211 215, 257, 258 hepatic venocclusive disease effects 211, 215, 216 infection outcomes 214, 215 timing of therapy 216 total parenteral nutrition 214 tumor effects 215 oral supplementation effects on chemotherapy-induced toxicity 257 pediatric cancer patient supplementation 280, 281 rationale for supplementation in cancer patients 256, 257 surgical cancer patient supplementation 246, 247 tumor utilization 255, 256 Glutathione S-transferase, carcinogen detoxification 4, 5 Growth hormone, anabolic effects in animal tumor models 263 Hematopoietic stem cell transplant allogeneic transplantation trends 208 donors 207, 208 graft-versus-host disease 208, 209, 216, 219, 220 incidence 207 nutrition body weight and outcomes 209, 210 enteral feeding children 218 complications 217 costs 217, 219 total parenteral nutrition 217 219 transition to oral diet 217, 218 tube placement 222, 223 glutamine absorption 223 clinical trials 211 215, 257, 258 hepatic venocclusive disease effects 211, 215, 216 infection outcomes 214, 215 timing of therapy 216 total parenteral nutrition 214 tumor effects 215 lipid modulation of graft-versus-host disease 219, 220 related effects 209 toxicity of marrow ablative regimens 210, 211 Homocysteine, colorectal cancer studies 101 Immunonutrition, see also Arginine, Glutamine, Omega-3 fatty acid, Ornithine - ketoglutarate ß 2 -adrenergic agonists 264 ethical considerations 269 formulations 264, 265 hormones 263 nutrient deficiencies in cancer patients 273 study design 268 surgical cancer patients gut-associated lymphoid tissue stimulation 252, 254 perioperative 248, 249 postoperative 246 248, 251, 252 preoperative 252, 253 randomized clinical trials 265 268 Initiation, tumors dietary modulation carcinogen activation 3, 4 carcinogen detoxification 4, 5 DNA repair 6 scavenging of reactive oxygen species 5, 6 overview 1, 2 Insulin, anabolic effects in animal tumor models 263 Insulin-like growth factors anabolic effects in animal tumor models 263 cancer risk 120, 121 Insulin resistance, cytokine mediation in cachexia 158, 159 Interferon-Á, cachexia role, see Cachexia Interleukin-6, cachexia role, see Cachexia 297
Leukemia-inhibitory factor, cachexia role, see Cachexia Lipoprotein lipase, cytokine regulation in cachexia 153, 154, 163 Lung cancer dietary effects alcohol 30 biases in studies 31, 32, 37 -carotene 27, 28 ß-carotene high-dose supplementation effects in smokers 42, 43, 45 49, 51 intervention studies 41, 42 mechanisms of prevention 41 oxidation products and carcinogenesis 43, 45 prospective cohort studies 24, 27, 28 vitamin C as reducing agent 50 52 vitamin E as reducing agent 50 52 fat intake 29, 30 flavonols 28, 29 folate 28 fruits and vegetables 24, 25, 27 29, 33, 35, 36, 40 lutein 27, 28 measurement error 32, 36, 37 multicollinearity of dietary variables 33 selenium 29 smoking as confounding factor in studies 32 vitamin C 24, 25, 27, 28 vitamin E 27 epidemiology 23 risk factors 23, 24, 39, 40 smoking carcinogens and oxidative damage 40 Lutein, lung cancer studies 27, 28 Meat, see Fat intake Medroxyprogesterone acetate, cachexia treatment 141 Megestrol acetate, therapy in enteral nutrition during head and neck radiotherapy 231, 236, 238 Methylenetetrahydrofolate reductase, polymorphisms in colon cancer 94 96 Muscle loss, see Cachexia Nutritional oncology anabolic competence as paradigm for nutritional intervention 197, 198 attitudes of oncologists 203, 204 bidirectional interplay of nutrition and chemotherapy 195 197 gut translocation of bacteria 191, 192 historical perspective 188, 189 hormonal factors 204, 205 immune response 190 192 parenteral nutrition 189, 190, 202, 203 protein requirements 205 standardized nutritional assessment 192 194 supplements voluntarily taken by cancer patients 202 weight loss grading 192, 193 survival outcome 188, 189 withholding of nutrition 204 Obesity measurements for cancer risk determination 120 prostate cancer risk 60, 63 tumor necrosis factor expression 164 Omega-3 fatty acid, see also Eicosapentaenoic acid clinical trials of immunonutrition 263 pediatric cancer patient supplementation 281 rationale for supplementation in cancer patients 261 surgical cancer patient supplementation 246 Ornithine -ketoglutarate burn patient supplementation 258 rationale for supplementation in cancer patients 258, 259 p53 knockout mouse studies of nutritional modulation of cancer 13, 14 marker in cancer trials 290, 291 mutation in tumor progression 12 Patient-Generated Subjective Global Assessment of Nutritional Status applications 193, 194 categorization of patients for nutritional intervention 194, 195 development 193 form 200 298
Pediatric cancer malnutrition and cachexia consequences 276 incidence 275, 282, 284 pathogenesis 276 pharmacotherapy 281, 282, 284 risk factors 278 nutritional support chemotherapy patients 283 detrimental effects 279 enteral nutrition 277, 279 goals 277 long-term support 277, 278 parenteral nutrition 277, 280 short-term support 277 supplements arginine 281 glutamine 280, 281 omega-3 fatty acids 281 types of cancers 275 Pentoxyphyllin, cachexia treatment 163 Percutaneous endoscopic gastrostomy head and neck radiotherapy patients 227, 229 232, 234 237 pediatric cancer patients 279 Progression, tumors dietary modulation angiogenesis 12 cell proliferation and apoptosis 7 10 immune surveillance 11 inflammation 10, 11 scavenging of reactive oxygen species 7 overview 1, 2, 11, 12 Proliferating cellular nuclear antigen, lung levels with ß-carotene supplementation in animals 46, 47 Promotion, tumors dietary modulation angiogenesis 12 cell proliferation and apoptosis 7 10 immune surveillance 11 inflammation 10, 11 scavenging of reactive oxygen species 7 overview 1, 2 Prostate cancer dietary effects alcohol 60 calcium 59, 60 ß-carotene 57, 58, 64, 65 dairy products 57 fat intake 57, 63, 64 fruits and vegetables 57, 58 potential impact on incidence 62 selenium 59, 63, 65 study designs 56, 57 vitamin D 59, 60 vitamin E 58, 59, 63 65 epidemiology 55 risk factors 55, 56, 60 Protein kinase C activation consequences 9 caloric restriction effects 10 phorbol ester interactions 8 Proteolysis-inducing factor assay 144 evidence for muscle catabolism in cancer cachexia 136, 137 glycosylation 138, 139 isolation 137, 138 lipid modulation 139, 140 mechanism of action 139 receptor 146 regulation 144 tumor specificity 144 Radiotherapy dietetic counseling 231, 233, 237 enteral nutrition during head and neck radiotherapy body weight 227 effects with surgery and/or chemotherapy 230, 231 fat reserves 227, 229 lean body mass 227, 236 markers for metabolic changes 229 outpatients 232, 234, 235 parenteral nutrition and complications 234 percutaneous endoscopic gastrostomy 227, 229 232, 234 237 quality of life 229, 230, 234, 237 study design 227 indications for nutritional support 231, 233 megestrol acetate therapy 231, 236, 238 side effects causing malnutrition 226 Reactive oxygen species, dietary modulation of carcinogenesis initiation 5, 6 promotion/progression 7 299
Resting energy expenditure, reduction with decreased food intake 239, 240 Retinoic acid receptor, lung levels with ß-carotene supplementation in animals 48 Retinoids, effects on tumor promotion/ progression 10 Selenium colorectal cancer studies 79 lung cancer studies 29 prostate cancer studies 59, 63, 65 Sensitivity, biomarker assays 286, 287, 289 Sex hormone-binding globulin, deficiency and breast cancer 120 Soy protein, breast cancer studies 116 Specificity, biomarker assays 286, 287, 289 Sucrose, colorectal cancer studies 74, 75 Surgery factors contributing to cachexia 239, 240 malnutrition and outcomes 240, 241 nutritional status assessment anthropometrics 241, 242 clinical parameters 241 laboratory tests 242 nutritional support arginine supplementation 246 cost analysis 254 daily requirements 245, 246 glutamine supplementation 246, 247 immunonutrition gut-associated lymphoid tissue stimulation 252, 254 perioperative 248, 249 postoperative 246 248, 251, 252 preoperative 252, 253 randomized clinical trials 265 268 multimodal treatment 250 omega-3 fatty acid supplementation 246 overview 242 routes enteral nutrition 243 245, 253 formulas for tube feeding 244, 245, 253 total parenteral nutrition 244, 252 Tea, colorectal cancer studies 81 Tocopherols, see Vitamin E Total parenteral nutrition hematopoietic stem cell transplant patients 217 219 pediatric cancer patients 280 Total parenteral nutrition cancer outcomes 202, 203 surgical cancer patients 244, 252 Transforming growth factor-, activation by tumor promoters 9 Transgenic mouse, studies of nutritional modulation of cancer 13, 14 Tumor necrosis factor cachexia role, see Cachexia expression in obesity 164 Uncoupling proteins, cachexia role 153 Vegetables, see Fruits and vegetables Vitamin A, breast cancer studies 109 Vitamin B 6, colorectal cancer studies 100, 101 Vitamin C breast cancer studies 110 colorectal cancer studies 78, 79 lung cancer studies 24, 25, 27, 28, 51 lung tissue levels in smokers 54 reduction of ß-carotene 50 52 Vitamin D colorectal cancer studies 77 prostate cancer studies 59, 60 Vitamin E breast cancer studies 110 colorectal cancer studies 78 80 lung cancer studies 27, 51 prostate cancer studies 58, 59, 63 65 reduction of ß-carotene 50 52 World Cancer Research Fund/American Institute for Cancer Research, findings on diet and cancer 119 300