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(AGEs) are a heterogeneous group of compounds formed by the non-enzymatic reaction between amino acids and reducing sugars, or dicarbonyls as intermediate compounds. Experimental studies suggest that AGEs may promote colorectal cancer, but prospective epidemiologic studies are inconclusive. We conducted a case\u2013control study nested within a large European cohort. Plasma concentrations of three protein-bound AGEs\u2014N\u03b5-(carboxy-methyl)lysine (CML), N\u03b5-(carboxy-ethyl)lysine (CEL) and N\u03b4-(5-hydro-5-methyl-4-imidazolon-2-yl)-ornithine (MG-H1)\u2014were measured by ultra-performance liquid chromatography\u2013tandem mass spectrometry in baseline samples collected from 1378 incident primary colorectal cancer cases and 1378 matched controls. Multivariable-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were computed using conditional logistic regression for colorectal cancer risk associated with CML, CEL, MG-H1, total AGEs, and [CEL+MG-H1: CML] and [CEL:MG-H1] ratios. Inverse colorectal cancer risk associations were observed for CML (OR comparing highest to lowest quintile, ORQ5 versus Q1 = 0.40, 95% CI: 0.27\u20130.59), MG-H1 (ORQ5 versus Q1 = 0.73, 95% CI: 0.53\u20131.00) and total AGEs (OR Q5 versus Q1 = 0.52, 95% CI: 0.37\u20130.73), whereas no association was observed for CEL. A higher [CEL+MG-H1: CML] ratio was associated with colorectal cancer risk (ORQ5 versus Q1 = 1.91, 95% CI: 1.31\u20132.79). The associations observed did not differ by sex, or by tumour anatomical sub-site. Although individual AGEs concentrations appear to be inversely associated with colorectal cancer risk, a higher ratio of methylglyoxal-derived AGEs versus those derived from glyoxal (calculated by [CEL+MG-H1: CML] ratio) showed a strong positive risk association. Further insight on the metabolism of AGEs and their dicarbonyls precursors, and their roles in colorectal cancer development is needed.<\/jats:p>","DOI":"10.1093\/carcin\/bgab026","type":"journal-article","created":{"date-parts":[[2021,3,25]],"date-time":"2021-03-25T12:10:32Z","timestamp":1616674232000},"page":"705-713","source":"Crossref","is-referenced-by-count":16,"title":["Plasma concentrations of advanced glycation end-products and colorectal cancer risk in the EPIC study"],"prefix":"10.1093","volume":"42","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0442-3284","authenticated-orcid":false,"given":"Elom K","family":"Aglago","sequence":"first","affiliation":[{"name":"Nutrition and Metabolism Section, International Agency for Research on Cancer, Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Casper G","family":"Schalkwijk","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, CARIM School for Cardiovascular Diseases, Maastricht University Medical Center, Maastricht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8648-4998","authenticated-orcid":false,"given":"Heinz","family":"Freisling","sequence":"additional","affiliation":[{"name":"Nutrition and Metabolism Section, International Agency for Research on Cancer, Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7805-9913","authenticated-orcid":false,"given":"Veronika","family":"Fedirko","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J","family":"Hughes","sequence":"additional","affiliation":[{"name":"Cancer Biology and Therapeutics Group (CBT), Conway Institute, School of Biomolecular and Biomedical Science (SBBS), University College Dublin, Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Jiao","sequence":"additional","affiliation":[{"name":"Department of Medicine, Baylor College of Medicine, Houston, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina C","family":"Dahm","sequence":"additional","affiliation":[{"name":"Department of Public Health, Aarhus University, Aarhus, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4788-503X","authenticated-orcid":false,"given":"Anja","family":"Olsen","sequence":"additional","affiliation":[{"name":"Department of Public Health, Aarhus University, Aarhus, Denmark"},{"name":"Danish Cancer Society Research Center, K\u00f8benhavn, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4385-2097","authenticated-orcid":false,"given":"Anne","family":"Tj\u00f8nneland","sequence":"additional","affiliation":[{"name":"Danish Cancer Society Research Center, K\u00f8benhavn, Denmark"},{"name":"Department of Public Health, University of Copenhagen, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6509-6555","authenticated-orcid":false,"given":"Verena","family":"Katzke","sequence":"additional","affiliation":[{"name":"Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4850-282X","authenticated-orcid":false,"given":"Theron","family":"Johnson","sequence":"additional","affiliation":[{"name":"Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias B","family":"Schulze","sequence":"additional","affiliation":[{"name":"Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany"},{"name":"Institute of Nutrition Science, University of Potsdam, Nuthetal, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krasimira","family":"Aleksandrova","sequence":"additional","affiliation":[{"name":"Institute of Nutrition Science, University of Potsdam, Nuthetal, Germany"},{"name":"Nutrition, Immunity and Metabolism Senior Scientist Group, Department of Nutrition and Gerontology, German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Nuthetal, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5758-9069","authenticated-orcid":false,"given":"Giovanna","family":"Masala","sequence":"additional","affiliation":[{"name":"Cancer Risk Factors and Life-Style Epidemiology Unit, Institute for Cancer Research, Prevention and Clinical Network-ISPRO, Florence, 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Troms\u00f8, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Torkjel","family":"Sandanger","sequence":"additional","affiliation":[{"name":"Faculty of Health Sciences, Department of Community Medicine, University of Troms\u00f8, The Arctic University of Norway, Troms\u00f8, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula","family":"Jakszyn","sequence":"additional","affiliation":[{"name":"Unit of Nutrition and Cancer, Cancer Epidemiology Research Programme, Catalan Institute of Oncology, Barcelona, Spain"},{"name":"Blanquerna School of Health Sciences, Ramon Llull University, Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria-Jose","family":"S\u00e1nchez","sequence":"additional","affiliation":[{"name":"Escuela Andaluza de Salud P\u00fablica (EASP), Granada, Spain"},{"name":"Instituto de Investigaci\u00f3n Biosanitaria ibs.Granada, Granada, Spain"},{"name":"Department of Preventive Medicine and Public Health, University of Granada, Granada, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Epidemiolog\u00eda y Salud P\u00fablica (CIBERESP), Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pilar","family":"Amiano","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Epidemiolog\u00eda y Salud P\u00fablica (CIBERESP), Madrid, Spain"},{"name":"Public Health Division of Gipuzkoa, BioDonostia Research Institute, Donostia-San Sebastian, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra M","family":"Colorado-Yohar","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Epidemiolog\u00eda y Salud P\u00fablica (CIBERESP), Madrid, Spain"},{"name":"Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca, Murcia, Spain"},{"name":"Research Group on Demography and Health, National Faculty of Public Health, University of Antioquia, Medell\u00edn, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aurelio Barricarte","family":"Gurrea","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Epidemiolog\u00eda y Salud P\u00fablica (CIBERESP), Madrid, Spain"},{"name":"Navarra Public Health Institute, Pamplona, Spain"},{"name":"Navarra Institute for Health Research (IdiSNA), Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5652-356X","authenticated-orcid":false,"given":"Aurora","family":"Perez-Cornago","sequence":"additional","affiliation":[{"name":"Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana-Lucia","family":"May\u00e9n","sequence":"additional","affiliation":[{"name":"Nutrition and Metabolism Section, International Agency for 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UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0573-1852","authenticated-orcid":false,"given":"Mazda","family":"Jenab","sequence":"additional","affiliation":[{"name":"Nutrition and Metabolism Section, International Agency for Research on Cancer, Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,3,29]]},"reference":[{"key":"2021070818180322900_CIT0001","doi-asserted-by":"crossref","first-page":"394","DOI":"10.3322\/caac.21492","article-title":"Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"68","author":"Bray","year":"2018","journal-title":"CA. 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