Dietary Advanced Glycation End-Products and Colorectal Cancer Risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) Study
Aglago, Elom K; Mayén, Ana-Lucia; Knaze, Viktoria; Freisling, Heinz; Fedirko, Veronika; Hughes, David J; Jiao, Li; Eriksen, Anne Kirstine; Tjønneland, Anne; Boutron-Ruault, Marie-Christine; Rothwell, Joseph A; Severi, Gianluca; Kaaks, Rudolf; Katzke, Verena; Schulze, Matthias B; Birukov, Anna; Palli, Domenico; Sieri, Sabina; Santucci de Magistris, Maria; Tumino, Rosario; Ricceri, Fulvio; Bueno-de-Mesquita, Bas; Derksen, Jeroen W G; Skeie, Guri; Gram, Inger Torhild; Sandanger, Torkjel; Quirós, J Ramón; Luján-Barroso, Leila; Sánchez, Maria-Jose; Amiano, Pilar; Chirlaque, María-Dolores; Gurrea, Aurelio Barricarte; Johansson, Ingegerd; Manjer, Jonas; Perez-Cornago, Aurora; Weiderpass, Elisabete; Gunter, Marc J; Heath, Alicia K; Schalkwijk, Casper G; Jenab, Mazda
(2021) Nutrients, volume 13, issue 9
(Article)
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
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dAGEs in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Dietary intakes of three major dAGEs: N"-carboxy-methyllysine (CML), N ԑ-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: HR Q5vs.Q1 = 0.92, 95% CI = 0.85–1.00) and MG-H1 (HR Q5vs.Q1 = 0.92, 95% CI = 0.85–1.00), but not for CEL (HR Q5vs.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.
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Keywords: Advanced glycation end-products, Colorectal cancer, Dietary exposure, Dietary glycation compounds, Food Science, Nutrition and Dietetics
ISSN: 2072-6643
Publisher: Multidisciplinary Digital Publishing Institute (MDPI)
Note: Funding Information: Acknowledgments: The authors would like to thank the EPIC study participants and staff for their valuable contribution to this research. The authors would also like to thank Bertrand Hemon for the preparation of the databases. The coordination of EPIC is financially supported by the International Agency for Research on Cancer (IARC) and also by the Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, which has additional infrastructure support provided by the NIHR Imperial Biomedical Research Centre (BRC). The national cohorts are supported by: Danish Cancer Society (Denmark); Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l’Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM) (France); German Cancer Aid, German Cancer Research Center (DKFZ), German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Federal Ministry of Education and Research (BMBF) (Germany); Associazione Italiana per la Ricerca sul Cancro (AIRC), Compagnia di San Paolo, and National Research Council (Italy); Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands); Health Research Fund (FIS), Instituto de Salud Carlos III (ISCIII), Regional Governments of Andalucía, Asturias, the Basque Country, Murcia, and Navarra, and the Catalan Institute of Oncology (ICO) (Spain); Swedish Cancer Society, Swedish Research Council, and County Councils of Skåne and Västerbotten (Sweden); Cancer Research UK (14136 to EPIC-Norfolk; C8221/A29017 to EPIC-Oxford), Medical Research Council (1000143 to EPIC-Norfolk; MR/M012190/1 to EPIC-Oxford) (United Kingdom). We are grateful to all of the participants who have been part of the project and to the many members of the study teams at the University of Cambridge who have enabled this research. We acknowledge the use of data from the EPIC-Aarhus cohort, PI Kim Overvad. We thank the CERCA Programme/Generalitat de Catalunya for institutional support. Funding Information: Funding: This work was funded by the Wereld Kanker Onderzoek Fonds (WKOF), as part of the World Cancer Research Fund (WCRF) International grant program (WCRF 2015-1391, P.I. Mazda Jenab, International Agency for Research on Cancer). This work was partially financially supported by the Fondation de France (FDF grant no. 00081166 to H. Freisling and FDF grant no. 00089811 to A.-L. Mayén). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland.
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