Dietary intake of advanced glycation endproducts and risk of hepatobiliary cancers: A multinational cohort study

• Type of Material: Article
• Authors: Ana-Lucia Mayén, International Agency for Research on Cancer (IARC‐WHO); Elom K Aglago, International Agency for Research on Cancer (IARC‐WHO); Viktoria Knaze, International Agency for Research on Cancer (IARC‐WHO); Reynalda Cordova, University of Vienna; Casper G Schalkwijk, Maastricht University; Karl-Heinz Wagner, University of Vienna; Krasimira Aleksandrova, German Institute of Human Nutrition Potsdam‐Rehbruecke; Veronika Fedirko, Emory University; Pekka Keski-Rahkonen, International Agency for Research on Cancer (IARC‐WHO); Michael F Leitzmann, University of Regensburg; Verena Katzke, Germany Cancer Research Center (DKFZ); Bernard Srour, Germany Cancer Research Center (DKFZ); Matthias B Schulze, German Inst Human Nutr Potsdam Rehbrucke; Giovanna Masala, Institute for Cancer Research Prevention and Clinical Network; Vittorio Krogh, Fdn IRCCS Ist Nazl Tumori Milano; Salvatore Panico, University of Naples Federico II; Rosario Tumino, Provincial Health Authority (ASP); Bas Bueno-de-Mesquita, National Institute for Public Health and the Environment (RIVM); Magritt Brustad, UiT The Arctic University of Norway; Antonio Agudo, Bellvitge Biomed Res Inst IDIBELL; María Dolores Chirlaque López, IMIB Arrixaca; Pilar Amiano, CIBER Epidemiología y Salud Pública (CIBERESP); Bodil Ohlsson, Lund University; Stina Ramne, Lund University; Dagfinn Aune, Imperial College London; Elisabete Weiderpass, International Agency for Research on Cancer (IARC‐WHO); Mazda Jenab, International Agency for Research on Cancer (IARC‐WHO); Heinz Freisling, International Agency for Research on Cancer (IARC‐WHO)
• Language: English
• Date: 2021-05-06
• Publisher: WILEY
• Publication Version: Final Published Version
• Copyright Statement: © 2021 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1002/ijc.33612
• Title of Journal or Parent Work: INTERNATIONAL JOURNAL OF CANCER
• Volume: 149
• Issue: 4
• Start Page: 854
• End Page: 864
• Grant/Funding Information: Fondation de France, Grant/Award Numbers: 00081166, 00089811; Wereld Kanker Onderzoek Fonds, Grant/Award Number: 2015‐1391
• Keywords: advanced glycation endproducts; Oncology; EPIC study; Life Sciences & Biomedicine; Science & Technology; bile duct cancers; gallbladder cancer; hepatocellular carcinoma
• Research Categories: Health Sciences, Nutrition

Abstract

Advanced glycation endproducts (AGEs) may contribute to liver carcinogenesis because of their proinflammatory and prooxidative properties. Diet is a major source of AGEs, but there is sparse human evidence on the role of AGEs intake in liver cancer etiology. We examined the association between dietary AGEs and the risk of hepatobiliary cancers in the European Prospective Investigation into Cancer and Nutrition prospective cohort (n = 450 111). Dietary intake of three AGEs, Nε-[carboxymethyl]lysine (CML), Nε-[1-carboxyethyl]lysine (CEL) and Nδ-[5-hydro-5-methyl-4-imidazolon-2-yl]-ornithine (MG-H1), was estimated using country-specific dietary questionnaires linked to an AGEs database. Cause-specific hazard ratios (HR) and their 95% confidence intervals (CI) for associations between dietary AGEs and risk of hepatocellular carcinoma (HCC), gallbladder and biliary tract cancers were estimated using multivariable Cox proportional hazard regression. After a median follow-up time of 14.9 years, 255 cases of HCC, 100 cases of gallbladder cancer and 173 biliary tract cancers were ascertained. Higher intakes of dietary AGEs were inversely associated with the risk of HCC (per 1 SD increment, HR-CML = 0.87, 95% CI: 0.76-0.99, HR-CEL = 0.84, 95% CI: 0.74-0.96 and HR-MH-G1 = 0.84, 95% CI: 0.74-0.97). In contrast, positive associations were observed with risk of gallbladder cancer (per 1 SD, HR-CML = 1.28, 95% CI: 1.05-1.56, HR-CEL = 1.17; 95% CI: 0.96-1.40, HR-MH-G1 = 1.27, 95% CI: 1.06-1.54). No associations were observed for cancers of the intra and extrahepatic bile ducts. Our findings suggest that higher intakes of dietary AGEs are inversely associated with the risk of HCC and positively associated with the risk of gallbladder cancer.