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

Research output: Contribution to journalJournal articleResearchpeer-review

  • Ana Lucia Mayén
  • 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 Agudo
  • María Dolores Chirlaque López
  • Pilar Amiano
  • Bodil Ohlsson
  • Dagfinn Aune
  • Elisabete Weiderpass
  • Mazda Jenab
  • Heinz Freisling

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.

Original languageEnglish
JournalInternational Journal of Cancer
Volume149
Issue number4
Pages (from-to)854-864
Number of pages11
ISSN0020-7136
DOIs
Publication statusPublished - 15 Aug 2021
Externally publishedYes

Bibliographical note

Funding Information:
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 especially thank Mr. Bertrand Hemon and Ms. Corinne Casagrande for preparing the EPIC databases. This study was funded by the Fondation de France (FDF, grant no. 00081166, Heinz Freisling and Reynalda Cordova and FDF grant no. 00089811, Ana‐Lucia Mayén). Mazda Jenab and Elom K. Aglago acknowledge funding by the Wereld Kanker Onderzoek Fonds (WKOF), as part of the World Cancer Research Fund (WCRF) International grant program (WCRF 2015‐1391, P.I. Dr. Mazda Jenab, International Agency for Research on Cancer). The coordination of EPIC is financially supported by the European Commission (DG‐SANCO); and the International Agency for Research on Cancer. The national cohorts are supported by Danish Cancer Society (Denmark); Ligue Contre le Cancer; Institut Gustave Roussy; Mutuelle Générale de l'Education Nationale; and Institut National de la Santé et de la Recherche Médicale (INSERM) (France); German Cancer Aid, German Cancer Research Center (DKFZ) and Federal Ministry of Education and Research (BMBF) (Germany); Italian Association for Research on Cancer (AIRC); National Research Council; and Associazione Iblea per la Ricerca Epidemiologica (AIRE‐ONLUS) Ragusa, Associazione Volontari Italiani Sangu (AVIS) Ragusa, Sicilian Government (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); and Statistics Netherlands (the Netherlands); Health Research Fund (FIS); Regional Governments of Andalucía, Asturias, Basque Country, Murcia (No. 6236) and Navarra; and the Centro de Investigación Biomédica en Red en Epidemiología y Salud Pública and Instituto de Salud Carlos II (ISCIII RETIC) (RD06/0020) (Spain); Health Research Fund (FIS)—Instituto de Salud Carlos III (ISCIII), Regional Governments of Andalucía, Asturias, Basque Country, Murcia and Navarra, and the Catalan Institute of Oncology—ICO (Spain); Swedish Cancer Society; Swedish Scientific Council; and Regional Government of Skåne and Västerbotten (Sweden); Cancer Research UK; Medical Research Council; Stroke Association; British Heart Foundation; Department of Health; Food Standards Agency; and the Wellcome Trust (UK). Cancer Research UK (14136 to EPIC‐Norfolk; C570/A16491 and C8221/A19170 and C8221/A29017 to EPIC‐Oxford), Medical Research Council (1000143 to EPIC‐Norfolk, MR/M012190/1 to EPIC‐Oxford) (United Kingdom). The EPIC‐Norfolk study (DOI 10.22025/2019.10.105.00004 ) has received funding from the Medical Research Council (MR/N003284/1 and MC‐UU_12015/1) and Cancer Research UK (C864/A14136). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the article.

Funding Information:
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 especially thank Mr. Bertrand Hemon and Ms. Corinne Casagrande for preparing the EPIC databases. This study was funded by the Fondation de France (FDF, grant no. 00081166, Heinz Freisling and Reynalda Cordova and FDF grant no. 00089811, Ana-Lucia May?n). Mazda Jenab and Elom K. Aglago acknowledge funding by the Wereld Kanker Onderzoek Fonds (WKOF), as part of the World Cancer Research Fund (WCRF) International grant program (WCRF 2015-1391, P.I. Dr. Mazda Jenab, International Agency for Research on Cancer). The coordination of EPIC is financially supported by the European Commission (DG-SANCO); and the International Agency for Research on Cancer. The national cohorts are supported by Danish Cancer Society (Denmark); Ligue Contre le Cancer; Institut Gustave Roussy; Mutuelle G?n?rale de l'Education Nationale; and Institut National de la Sant? et de la Recherche M?dicale (INSERM) (France); German Cancer Aid, German Cancer Research Center (DKFZ) and Federal Ministry of Education and Research (BMBF) (Germany); Italian Association for Research on Cancer (AIRC); National Research Council; and Associazione Iblea per la Ricerca Epidemiologica (AIRE-ONLUS) Ragusa, Associazione Volontari Italiani Sangu (AVIS) Ragusa, Sicilian Government (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); and Statistics Netherlands (the Netherlands); Health Research Fund (FIS); Regional Governments of Andaluc?a, Asturias, Basque Country, Murcia (No. 6236) and Navarra; and the Centro de Investigaci?n Biom?dica en Red en Epidemiolog?a y Salud P?blica and Instituto de Salud Carlos II (ISCIII RETIC) (RD06/0020) (Spain); Health Research Fund (FIS)?Instituto de Salud Carlos III (ISCIII), Regional Governments of Andaluc?a, Asturias, Basque Country, Murcia and Navarra, and the Catalan Institute of Oncology?ICO (Spain); Swedish Cancer Society; Swedish Scientific Council; and Regional Government of Sk?ne and V?sterbotten (Sweden); Cancer Research UK; Medical Research Council; Stroke Association; British Heart Foundation; Department of Health; Food Standards Agency; and the Wellcome Trust (UK). Cancer Research UK (14136 to EPIC-Norfolk; C570/A16491 and C8221/A19170 and C8221/A29017 to EPIC-Oxford), Medical Research Council (1000143 to EPIC-Norfolk, MR/M012190/1 to EPIC-Oxford) (United Kingdom). The EPIC-Norfolk study (DOI 10.22025/2019.10.105.00004) has received funding from the Medical Research Council (MR/N003284/1 and MC-UU_12015/1) and Cancer Research UK (C864/A14136). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the article.

Publisher Copyright:
© 2021 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.

    Research areas

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

ID: 288801436