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 Tjonneland, 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 Sanchez, Pilar Amiano, Sandra M. Colorado-Yohar, Aurelio Barricarte Gurrea, Aurora Perez-Cornago, Ana-Lucia Mayen, Elisabete Weiderpass, Marc J. Gunter, Alicia K. Heath, Mazda Jenab*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

3 Citations (Web of Science)

Abstract

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-N epsilon-(carboxy-methyl)lysine (CML), N epsilon-(carboxy-ethyl)lysine (CEL) and N delta-(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
JournalCarcinogenesis
Volume42
Issue number5
DOIs
Publication statusPublished - May 2021

Keywords

  • SOLUBLE RECEPTOR
  • AGE
  • METHYLGLYOXAL
  • RECOGNITION
  • EXPRESSION
  • STRESS
  • FOOD

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