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 - Tjonneland, 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 - Sanchez, Maria-Jose

AU - Amiano, Pilar

AU - Colorado-Yohar, Sandra M.

AU - Gurrea, Aurelio Barricarte

AU - Perez-Cornago, Aurora

AU - Mayen, Ana-Lucia

AU - Weiderpass, Elisabete

AU - Gunter, Marc J.

AU - Heath, Alicia K.

AU - Jenab, Mazda

PY - 2021

Y1 - 2021

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-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.

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-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.

KW - SOLUBLE RECEPTOR

KW - AGE

KW - METHYLGLYOXAL

KW - RECOGNITION

KW - EXPRESSION

KW - STRESS

KW - FOOD

U2 - 10.1093/carcin/bgab026

DO - 10.1093/carcin/bgab026

M3 - Journal article

C2 - 33780524

VL - 42

SP - 705

EP - 713

JO - Carcinogenesis

JF - Carcinogenesis

SN - 0143-3334

IS - 5

ER -