title: Consumption of Red/Processed Meat and Colorectal Carcinoma: Possible Mechanisms Underlying the Significant Association.
abstract: Epidemiology and experimental studies provide an overwhelming support of the notion that diets high in red or processed meat accompany an elevated risk of developing pre-neoplastic colorectal adenoma and frank colorectal carcinoma (CRC). The underlying mechanisms are disputed; thus several hypotheses have been proposed. A large body of reports converges, however, on haem and nitrosyl haem as major contributors to the CRC development, presumably acting through various mechanisms. Apart from a potentially higher intestinal mutagenic load among consumers on a diet rich in red/processed meat, other mechanisms involving subtle interference with colorectal stem/progenitor cell survival or maturation are likewise at play. From an overarching perspective, suggested candidate mechanisms for red/processed meat-induced CRC appear as three partly overlapping tenets: (i) increased N-nitrosation/oxidative load leading to DNA adducts and lipid peroxidation in the intestinal epithelium, (ii) proliferative stimulation of the epithelium through haem or food-derived metabolites that either act directly or subsequent to conversion, and (iii) higher inflammatory response, which may trigger a wide cascade of pro-malignant processes. In this review, we summarize and discuss major findings of the area in the context of potentially pertinent mechanisms underlying the above-mentioned association between consumption of red/processed meat and increased risk of developing CRC.
authors: a Cancer Pharmacology & Computational Medicine, Department of Medical Sciences, Uppsala University and Uppsala Academic Hospital , Uppsala , Sweden.
authors: Ulf
authors: U
authors: Hammerling
authors: b Sahlgrenska Biobank, Gothia Forum, Sahlgrenska University Hospital , Gothenburg , Sweden.
authors: Jonas
authors: J
authors: Bergman Laurila
authors: c Institute of Environmental Medicine, The Karolinska Institute , Stockholm , Sweden.|d Knowledge Intensive Products and Services, VTT Technical Research Centre of Finland , Turku , Finland.
authors: Roland
authors: R
authors: Grafström
authors: e Clinical Microbiology & Infectious Medicine, Department of Medical Sciences, Uppsala University and Uppsala Academic Hospital , Uppsala , Sweden.
authors: Nils-Gunnar
authors: NG
authors: Ilbäck
mesh_terms: D000230:Adenocarcinoma / Q000209:etiology / Q000235:genetics / Q000473:pathology; D000236:Adenoma / Q000209:etiology / Q000235:genetics; D000818:Animals; D001120:Arginine / Q000009:adverse effects; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000209:etiology* / Q000235:genetics / Q000473:pathology; D044127:Epigenesis, Genetic / Q000502:physiology; D043371:Fatty Acids, Omega-6 / Q000009:adverse effects; D005247:Feeding Behavior; D005511:Food Handling; D053823:Hedgehog Proteins / Q000378:metabolism; D006418:Heme / Q000009:adverse effects; D006801:Humans; D007422:Intestines / Q000473:pathology / Q000503:physiopathology; D009153:Mutagens / Q000009:adverse effects; D014411:Neoplastic Stem Cells / Q000473:pathology; D009603:Nitroso Compounds / Q000009:adverse effects / Q000378:metabolism; D051880:Receptors, Notch / Q000378:metabolism; D000069466:Red Meat / Q000009:adverse effects*; D012307:Risk Factors; D060449:Wnt Signaling Pathway
chemical_list: D019485:Bone Morphogenetic Proteins; D043371:Fatty Acids, Omega-6; D053823:Hedgehog Proteins; D009153:Mutagens; D009603:Nitroso Compounds; D051880:Receptors, Notch; D006418:Heme; D001120:Arginine
keywords: Dietary patterns; N-nitroso compounds; fat peroxidation; haem; morphogenetic pathways; nitrosyl-haem; red/processed meat, intestinal carcinogenesis