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dc.contributor.authorGunter, Marc J.
dc.contributor.authorLeitzmann, Michael F.
dc.date.accessioned2009-05-22T08:51:06Z
dc.date.available2009-05-22T08:51:06Z
dc.date.issued2006-03
dc.identifier.citationJ. Nutr. Biochem. 2006, 17 (3):145-156en
dc.identifier.issn0955-2863
dc.identifier.pmid16426829
dc.identifier.doi10.1016/j.jnutbio.2005.06.011
dc.identifier.urihttp://hdl.handle.net/10146/68773
dc.descriptionKEYWORDS - CLASSIFICATION: Adipocytes;Animals;Body Size;cancer epidemiology;complications;Cell Differentiation;Chronic Disease;Colonic Neoplasms;Diet;epidemiology;Energy Metabolism;Exercise;Family;genetics;Growth Hormone;Humans;Inflammation;Insulin;Insulin-Like Growth Factor I;Insulin-Like Growth Factor II;Insulin Resistance;lifestyle modulation of cancer & cancer biomarkers;metabolism;Obesity;Signal Transduction.en
dc.description.abstractThere is increasing evidence that dysregulation of energy homeostasis is associated with colorectal carcinogenesis. Epidemiological data have consistently demonstrated a positive relation between increased body size and colorectal malignancy, whereas mechanistic studies have sought to uncover obesity-related carcinogenic pathways. The phenomenon of "insulin resistance" or the impaired ability to normalize plasma glucose levels has formed the core of these pathways, but other mechanisms have also been advanced. Obesity-induced insulin resistance leads to elevated levels of plasma insulin, glucose and fatty acids. Exposure of the colonocyte to heightened concentrations of insulin may induce a mitogenic effect within these cells, whereas exposure to glucose and fatty acids may induce metabolic perturbations, alterations in cell signaling pathways and oxidative stress. The importance of chronic inflammation in the pathogenesis of obesity has recently been highlighted and may represent an additional mechanism linking increased adiposity to colorectal carcinogenesis. This review provides an overview of the epidemiology of body size and colorectal neoplasia and outlines current knowledge of putative mechanisms advanced to explain this relation. Family based studies have shown that the propensity to become obese is heritable, but this is only manifest in conditions of excess energy intake over expenditure. Inheritance of a genetic profile that predisposes to increased body size may also be predictive of colorectal cancer. Genomewide scans, linkage studies and candidate gene investigations have highlighted more than 400 chromosomal regions that may harbor variants that predispose to increased body size. The genetics underlying the pathogenesis of obesity are likely to be complex, but variants in a range of different genes have already been associated with increased body size and insulin resistance. These include genes encoding elements of insulin signaling, adipocyte metabolism and differentiation, and regulation of energy expenditure. A number of investigators have begun to study genetic variants within these pathways in relation to colorectal neoplasia, but at present data remain limited to a handful of studies. These pathways will be discussed with particular reference to genetic polymorphisms that have been associated with obesity and insulin resistance.
dc.language.isoenen
dc.relation.urlhttp://linkinghub.elsevier.com/retrieve/pii/S0955-2863(05)00255-Xen
dc.subjectBody sizeen
dc.subjectObesityen
dc.subjectColorectal canceren
dc.subjectInsulin resistanceen
dc.subjectGeneticsen
dc.subject.meshAdipocytes
dc.subject.meshAnimals
dc.subject.meshBody Size
dc.subject.meshCell Differentiation
dc.subject.meshChronic Disease
dc.subject.meshColonic Neoplasms
dc.subject.meshDiet
dc.subject.meshEnergy Metabolism
dc.subject.meshExercise
dc.subject.meshGrowth Hormone
dc.subject.meshHumans
dc.subject.meshInflammation
dc.subject.meshInsulin
dc.subject.meshInsulin Resistance
dc.subject.meshInsulin-Like Growth Factor I
dc.subject.meshInsulin-Like Growth Factor II
dc.subject.meshObesity
dc.subject.meshSignal Transduction
dc.titleObesity and colorectal cancer: epidemiology, mechanisms and candidate genes.en
dc.typeArticleen
dc.identifier.journalThe Journal of nutritional biochemistryen
html.description.abstractThere is increasing evidence that dysregulation of energy homeostasis is associated with colorectal carcinogenesis. Epidemiological data have consistently demonstrated a positive relation between increased body size and colorectal malignancy, whereas mechanistic studies have sought to uncover obesity-related carcinogenic pathways. The phenomenon of "insulin resistance" or the impaired ability to normalize plasma glucose levels has formed the core of these pathways, but other mechanisms have also been advanced. Obesity-induced insulin resistance leads to elevated levels of plasma insulin, glucose and fatty acids. Exposure of the colonocyte to heightened concentrations of insulin may induce a mitogenic effect within these cells, whereas exposure to glucose and fatty acids may induce metabolic perturbations, alterations in cell signaling pathways and oxidative stress. The importance of chronic inflammation in the pathogenesis of obesity has recently been highlighted and may represent an additional mechanism linking increased adiposity to colorectal carcinogenesis. This review provides an overview of the epidemiology of body size and colorectal neoplasia and outlines current knowledge of putative mechanisms advanced to explain this relation. Family based studies have shown that the propensity to become obese is heritable, but this is only manifest in conditions of excess energy intake over expenditure. Inheritance of a genetic profile that predisposes to increased body size may also be predictive of colorectal cancer. Genomewide scans, linkage studies and candidate gene investigations have highlighted more than 400 chromosomal regions that may harbor variants that predispose to increased body size. The genetics underlying the pathogenesis of obesity are likely to be complex, but variants in a range of different genes have already been associated with increased body size and insulin resistance. These include genes encoding elements of insulin signaling, adipocyte metabolism and differentiation, and regulation of energy expenditure. A number of investigators have begun to study genetic variants within these pathways in relation to colorectal neoplasia, but at present data remain limited to a handful of studies. These pathways will be discussed with particular reference to genetic polymorphisms that have been associated with obesity and insulin resistance.


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