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

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

  • Elom K. Aglago
  • Casper G. Schalkwijk
  • Heinz Freisling
  • Veronika Fedirko
  • David J. Hughes
  • Li Jiao
  • Christina C. Dahm
  • Anja Olsen
  • Verena Katzke
  • Theron Johnson
  • Matthias B. Schulze
  • Krasimira Aleksandrova
  • Giovanna Masala
  • Sabina Sieri
  • Vittorio Simeon
  • Rosario Tumino
  • Alessandra Macciotta
  • Bas Bueno-de-Mesquita
  • Guri Skeie
  • Inger 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

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.

OriginalsprogEngelsk
TidsskriftCarcinogenesis
Vol/bind42
Udgave nummer5
Sider (fra-til)705-713
Antal sider9
ISSN0143-3334
DOI
StatusUdgivet - 2021

ID: 272499819