Dietary Advanced Glycation End-Products and Colorectal Cancer Risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) Study

Author:

Aglago Elom K.,Mayén Ana-Lucia,Knaze Viktoria,Freisling HeinzORCID,Fedirko Veronika,Hughes David J.ORCID,Jiao LiORCID,Eriksen Anne Kirstine,Tjønneland AnneORCID,Boutron-Ruault Marie-Christine,Rothwell Joseph A.,Severi Gianluca,Kaaks Rudolf,Katzke Verena,Schulze Matthias B.ORCID,Birukov AnnaORCID,Palli DomenicoORCID,Sieri SabinaORCID,Santucci de Magistris Maria,Tumino Rosario,Ricceri Fulvio,Bueno-de-Mesquita Bas,Derksen Jeroen W. G.ORCID,Skeie GuriORCID,Gram Inger TorhildORCID,Sandanger Torkjel,Quirós J. Ramón,Luján-Barroso LeilaORCID,Sánchez Maria-Jose,Amiano Pilar,Chirlaque María-Dolores,Gurrea Aurelio Barricarte,Johansson IngegerdORCID,Manjer Jonas,Perez-Cornago Aurora,Weiderpass ElisabeteORCID,Gunter Marc J.,Heath Alicia K.ORCID,Schalkwijk Casper G.,Jenab Mazda

Abstract

Dietary advanced glycation end-products (dAGEs) have been hypothesized to be associated with a higher risk of colorectal cancer (CRC) by promoting inflammation, metabolic dysfunction, and oxidative stress in the colonic epithelium. However, evidence from prospective cohort studies is scarce and inconclusive. We evaluated CRC risk associated with the intake of dAGEs in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Dietary intakes of three major dAGEs: Nε-carboxy-methyllysine (CML), Nε-carboxyethyllysine (CEL), and Nδ-(5-hydro-5-methyl-4-imidazolon-2-yl)-ornithine (MG-H1) were estimated in 450,111 participants (median follow-up = 13 years, with 6162 CRC cases) by matching to a detailed published European food composition database. Hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations of dAGEs with CRC were computed using multivariable-adjusted Cox regression models. Inverse CRC risk associations were observed for CML (HR comparing extreme quintiles: HRQ5vs.Q1 = 0.92, 95% CI = 0.85–1.00) and MG-H1 (HRQ5vs.Q1 = 0.92, 95% CI = 0.85–1.00), but not for CEL (HRQ5vs.Q1 = 0.97, 95% CI = 0.89–1.05). The associations did not differ by sex or anatomical location of the tumor. Contrary to the initial hypothesis, our findings suggest an inverse association between dAGEs and CRC risk. More research is required to verify these findings and better differentiate the role of dAGEs from that of endogenously produced AGEs and their precursor compounds in CRC development.

Funder

World Cancer Research Fund International

Publisher

MDPI AG

Subject

Food Science,Nutrition and Dietetics

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