Plasma concentrations of advanced glycation end-products and colorectal cancer risk in the EPIC study

Elom K. Aglago, Casper G. Schalkwijk, Heinz Freisling, Veronika Fedirko, David J. Hughes, Li Jiao, Christina C. Dahm, Anja Olsen, Anne Tjønneland, Verena Katzke, Theron Johnson, Matthias B. Schulze, Krasimira Aleksandrova, Giovanna Masala, Sabina Sieri, Vittorio Simeon, Rosario Tumino, Alessandra Macciotta, Bas Bueno-De-Mesquita, Guri SkeieInger Torhild Gram, Torkjel Sandanger, Paula Jakszyn, Maria Jose Sánchez, Pilar Amiano, Sandra M. Colorado-Yohar, Aurelio Barricarte Gurrea, Aurora Perez-Cornago, Ana Lucia Mayén, Elisabete Weiderpass, Marc J. Gunter, Alicia K. Heath, Mazda Jenab

Research output: Indexed journal article Articlepeer-review

7 Citations (Scopus)


Advanced glycation end-products (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-control study nested within a large European cohort. Plasma concentrations of three protein-bound AGEs - Nϵ-(carboxy-methyl)lysine (CML), Nϵ-(carboxy-ethyl)lysine (CEL) and Nδ-(5-hydro-5-methyl-4-imidazolon-2-yl)-ornithine (MG-H1) - were measured by ultra-performance liquid chromatography-tandem 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: 0.27-0.59), MG-H1 (ORQ5 versus Q1 = 0.73, 95% CI: 0.53-1.00) and total AGEs (OR Q5 versus Q1 = 0.52, 95% CI: 0.37-0.73), 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: 1.31-2.79). 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.

Original languageEnglish
Pages (from-to)705-713
Number of pages9
Issue number5
Publication statusPublished - 29 Mar 2021


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