TY - JOUR

T1 - Dietary intake of advanced glycation endproducts and risk of hepatobiliary cancers

T2 - A multinational cohort study

AU - Mayén, Ana Lucia

AU - Aglago, Elom K.

AU - Knaze, Viktoria

AU - Cordova, Reynalda

AU - Schalkwijk, Casper G.

AU - Wagner, Karl Heinz

AU - Aleksandrova, Krasimira

AU - Fedirko, Veronika

AU - Keski-Rahkonen, Pekka

AU - Leitzmann, Michael F.

AU - Katzke, Verena

AU - Srour, Bernard

AU - Schulze, Matthias B.

AU - Masala, Giovanna

AU - Krogh, Vittorio

AU - Panico, Salvatore

AU - Tumino, Rosario

AU - Bueno-de-Mesquita, Bas

AU - Brustad, Magritt

AU - Agudo, Antonio

AU - Chirlaque López, María Dolores

AU - Amiano, Pilar

AU - Ohlsson, Bodil

AU - Ramne, Stina

AU - Aune, Dagfinn

AU - Weiderpass, Elisabete

AU - Jenab, Mazda

AU - Freisling, Heinz

N1 - 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.

PY - 2021

Y1 - 2021

N2 - 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.

AB - 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.

KW - advanced glycation endproducts

KW - bile duct cancers

KW - EPIC study

KW - gallbladder cancer

KW - hepatocellular carcinoma

U2 - 10.1002/ijc.33612

DO - 10.1002/ijc.33612

M3 - Journal article

C2 - 33899229

AN - SCOPUS:85105630736

VL - 149

SP - 854

EP - 864

JO - Acta - Unio Internationalis Contra Cancrum

JF - Acta - Unio Internationalis Contra Cancrum

SN - 0898-6924

IS - 4

ER -