TY - JOUR
T1 - Plasma concentrations of advanced glycation end-products and colorectal cancer risk in the EPIC study
AU - Aglago, Elom K.
AU - Schalkwijk, Casper G.
AU - Freisling, Heinz
AU - Fedirko, Veronika
AU - Hughes, David J.
AU - Jiao, Li
AU - Dahm, Christina C.
AU - Olsen, Anja
AU - Tjønneland, Anne
AU - Katzke, Verena
AU - Johnson, Theron
AU - Schulze, Matthias B.
AU - Aleksandrova, Krasimira
AU - Masala, Giovanna
AU - Sieri, Sabina
AU - Simeon, Vittorio
AU - Tumino, Rosario
AU - Macciotta, Alessandra
AU - Bueno-De-Mesquita, Bas
AU - Skeie, Guri
AU - Gram, Inger Torhild
AU - Sandanger, Torkjel
AU - Jakszyn, Paula
AU - Sánchez, Maria Jose
AU - Amiano, Pilar
AU - Colorado-Yohar, Sandra M.
AU - Gurrea, Aurelio Barricarte
AU - Perez-Cornago, Aurora
AU - Mayén, Ana Lucia
AU - Weiderpass, Elisabete
AU - Gunter, Marc J.
AU - Heath, Alicia K.
AU - Jenab, Mazda
N1 - Publisher Copyright:
© 2021 The Author(s) 2021. Published by Oxford University Press. All rights reserved. For Permissions, please email: [email protected].
Funding (WCRF 2015/1391, PI: M.J.) was obtained from Wereld Kanker Onderzoek Fonds (WKOF), as part of the World Cancer Research Fund International grant programme.
PY - 2021/3/29
Y1 - 2021/3/29
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85107318932&partnerID=8YFLogxK
UR - https://www.webofscience.com/wos/woscc/full-record/WOS:000661465600005
U2 - 10.1093/carcin/bgab026
DO - 10.1093/carcin/bgab026
M3 - Article
C2 - 33780524
AN - SCOPUS:85107318932
SN - 0143-3334
VL - 42
SP - 705
EP - 713
JO - Carcinogenesis
JF - Carcinogenesis
IS - 5
ER -
