Plasma concentrations of advanced glycation end-products and colorectal cancer risk in the EPIC study.
Adult
Aged
Chromatography, Liquid
Cohort Studies
Colorectal Neoplasms
/ blood
Female
Genetic Association Studies
Genetic Predisposition to Disease
Glycation End Products, Advanced
/ blood
Humans
Imidazoles
/ blood
Lysine
/ analogs & derivatives
Male
Middle Aged
Odds Ratio
Ornithine
/ analogs & derivatives
Tandem Mass Spectrometry
Journal
Carcinogenesis
ISSN: 1460-2180
Titre abrégé: Carcinogenesis
Pays: England
ID NLM: 8008055
Informations de publication
Date de publication:
28 05 2021
28 05 2021
Historique:
received:
16
12
2020
revised:
02
03
2021
accepted:
25
03
2021
pubmed:
30
3
2021
medline:
30
9
2021
entrez:
29
3
2021
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 33780524
pii: 6199858
doi: 10.1093/carcin/bgab026
pmc: PMC8162627
doi:
Substances chimiques
Glycation End Products, Advanced
0
Imidazoles
0
N(6)-carboxyethyllysine
0
Ndelta-(5-hydro-5-methyl-4-imidazolon-2-yl)ornithine
0
N(6)-carboxymethyllysine
70YDX3Z2O7
Ornithine
E524N2IXA3
Lysine
K3Z4F929H6
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
705-713Subventions
Organisme : Medical Research Council
ID : MR/N003284/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : G0401527
Pays : United Kingdom
Organisme : Medical Research Council
ID : G1000143
Pays : United Kingdom
Organisme : Cancer Research UK
ID : 14136
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/M012190/1
Pays : United Kingdom
Informations de copyright
© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
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