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

Ana-Lucia Mayen, Elom K. Aglago, Viktoria Knaze, Reynalda Cordova, Casper G. Schalkwijk, Karl-Heinz Wagner, Krasimira Aleksandrova, Veronika Fedirko, Pekka Keski-Rahkonen, Michael F. Leitzmann, Verena Katzke, Bernard Srour, Matthias B. Schulze, Giovanna Masala, Vittorio Krogh, Salvatore Panico, Rosario Tumino, Bas Bueno-de-Mesquita, Magritt Brustad, Antonio AgudoMaria Dolores Chirlaque Lopez, Pilar Amiano, Bodil Ohlsson, Stina Ramne, Dagfinn Aune, Elisabete Weiderpass, Mazda Jenab, Heinz Freisling*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


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, N-epsilon-[carboxymethyl]lysine (CML), N-epsilon-[1-carboxyethyl]lysine (CEL) and N-delta-[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.

Original languageEnglish
Pages (from-to)854-864
Number of pages11
JournalInternational Journal of Cancer
Issue number4
Publication statusPublished - 15 Aug 2021


  • advanced glycation endproducts
  • bile duct cancers
  • EPIC study
  • gallbladder cancer
  • hepatocellular carcinoma


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