Dietary Advanced Glycation End-Products and Colorectal Cancer Risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) Study

Elom K Aglago; Ana-Lucia Mayén; Viktoria Knaze; Heinz Freisling; Veronika Fedirko; David J Hughes; Li Jiao; Anne Kirstine Eriksen; Anne Tjønneland; Marie-Christine Boutron-Ruault; Joseph A Rothwell; Gianluca Severi; Rudolf Kaaks; Verena Katzke; Matthias B Schulze; Anna Birukov; Domenico Palli; Sabina Sieri; Maria Santucci de Magistris; Rosario Tumino; Fulvio Ricceri; Bas Bueno-de-Mesquita; Jeroen W G Derksen; Guri Skeie; Inger Torhild Gram; Torkjel Sandanger; J Ramón Quirós; Leila Luján-Barroso; Maria-Jose Sánchez; Pilar Amiano; María-Dolores Chirlaque; Aurelio Barricarte Gurrea; Ingegerd Johansson; Jonas Manjer; Aurora Perez-Cornago; Elisabete Weiderpass; Marc J Gunter; Alicia K Heath; Casper G Schalkwijk; Mazda Jenab

doi:10.3390/nu13093132

Dietary Advanced Glycation End-Products and Colorectal Cancer Risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) Study

Elom K Aglago, Ana-Lucia Mayén, Viktoria Knaze, Heinz Freisling, Veronika Fedirko, David J Hughes, Li Jiao, Anne Kirstine Eriksen, Anne Tjønneland, Marie-Christine Boutron-Ruault, Joseph A Rothwell, Gianluca Severi, Rudolf Kaaks, Verena Katzke, Matthias B Schulze, Anna Birukov, Domenico Palli, Sabina Sieri, Maria Santucci de Magistris, Rosario TuminoFulvio Ricceri, Bas Bueno-de-Mesquita, Jeroen W G Derksen, Guri Skeie, Inger Torhild Gram, Torkjel Sandanger, J Ramón Quirós, Leila Luján-Barroso, Maria-Jose Sánchez, Pilar Amiano, María-Dolores Chirlaque, Aurelio Barricarte Gurrea, Ingegerd Johansson, Jonas Manjer, Aurora Perez-Cornago, Elisabete Weiderpass, Marc J Gunter, Alicia K Heath, Casper G Schalkwijk, Mazda Jenab

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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 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.

Original language	English
Article number	3132
Journal	Nutrients
Volume	13
Issue number	9
DOIs	https://doi.org/10.3390/nu13093132
Publication status	Published - 8 Sept 2021

Keywords

Advanced glycation end-products
Colorectal cancer
Dietary exposure
Dietary glycation compounds

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nutrients-13-03132Final published version, 320 KBLicence: CC BY

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Aglago, E. K., Mayén, A.-L., Knaze, V., Freisling, H., Fedirko, V., Hughes, D. J., Jiao, L., Eriksen, A. K., Tjønneland, A., Boutron-Ruault, M.-C., Rothwell, J. A., Severi, G., Kaaks, R., Katzke, V., Schulze, M. B., Birukov, A., Palli, D., Sieri, S., Santucci de Magistris, M., ... Jenab, M. (2021). Dietary Advanced Glycation End-Products and Colorectal Cancer Risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) Study. Nutrients, 13(9), Article 3132. https://doi.org/10.3390/nu13093132

@article{88ee8f488b13449a80d907cf6c50b81f,

title = "Dietary Advanced Glycation End-Products and Colorectal Cancer Risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) Study",

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 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. ",

keywords = "Advanced glycation end-products, Colorectal cancer, Dietary exposure, Dietary glycation compounds",

author = "Aglago, {Elom K} and Ana-Lucia May{\'e}n and Viktoria Knaze and Heinz Freisling and Veronika Fedirko and Hughes, {David J} and Li Jiao and Eriksen, {Anne Kirstine} and Anne Tj{\o}nneland and Marie-Christine Boutron-Ruault and Rothwell, {Joseph A} and Gianluca Severi and Rudolf Kaaks and Verena Katzke and Schulze, {Matthias B} and Anna Birukov and Domenico Palli and Sabina Sieri and {Santucci de Magistris}, Maria and Rosario Tumino and Fulvio Ricceri and Bas Bueno-de-Mesquita and Derksen, {Jeroen W G} and Guri Skeie and Gram, {Inger Torhild} and Torkjel Sandanger and Quir{\'o}s, {J Ram{\'o}n} and Leila Luj{\'a}n-Barroso and Maria-Jose S{\'a}nchez and Pilar Amiano and Mar{\'i}a-Dolores Chirlaque and Gurrea, {Aurelio Barricarte} and Ingegerd Johansson and Jonas Manjer and Aurora Perez-Cornago and Elisabete Weiderpass and Gunter, {Marc J} and Heath, {Alicia K} and Schalkwijk, {Casper G} and Mazda Jenab",

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 G{\'e}n{\'e}rale de l{\textquoteright}Education Nationale, Institut National de la Sant{\'e} et de la Recherche M{\'e}dicale (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 Andaluc{\'i}a, 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 Sk{\aa}ne and V{\"a}sterbotten (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. May{\'e}n). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Publisher Copyright: {\textcopyright} 2021 by the authors. Licensee MDPI, Basel, Switzerland.",

year = "2021",

month = sep,

day = "8",

doi = "10.3390/nu13093132",

language = "English",

volume = "13",

number = "9",

}

Aglago, EK, Mayén, A-L, Knaze, V, Freisling, H, Fedirko, V, Hughes, DJ, Jiao, L, Eriksen, AK, Tjønneland, A, Boutron-Ruault, M-C, Rothwell, JA, Severi, G, Kaaks, R, Katzke, V, Schulze, MB, Birukov, A, Palli, D, Sieri, S, Santucci de Magistris, M, Tumino, R, Ricceri, F, Bueno-de-Mesquita, B, Derksen, JWG, Skeie, G, Gram, IT, Sandanger, T, Quirós, JR, Luján-Barroso, L, Sánchez, M-J, Amiano, P, Chirlaque, M-D, Gurrea, AB, Johansson, I, Manjer, J, Perez-Cornago, A, Weiderpass, E, Gunter, MJ, Heath, AK, Schalkwijk, CG & Jenab, M 2021, 'Dietary Advanced Glycation End-Products and Colorectal Cancer Risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) Study', Nutrients, vol. 13, no. 9, 3132. https://doi.org/10.3390/nu13093132

TY - JOUR

T1 - Dietary Advanced Glycation End-Products and Colorectal Cancer Risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) Study

AU - Aglago, Elom K

AU - Mayén, Ana-Lucia

AU - Knaze, Viktoria

AU - Freisling, Heinz

AU - Fedirko, Veronika

AU - Hughes, David J

AU - Jiao, Li

AU - Eriksen, Anne Kirstine

AU - Tjønneland, Anne

AU - Boutron-Ruault, Marie-Christine

AU - Rothwell, Joseph A

AU - Severi, Gianluca

AU - Kaaks, Rudolf

AU - Katzke, Verena

AU - Schulze, Matthias B

AU - Birukov, Anna

AU - Palli, Domenico

AU - Sieri, Sabina

AU - Santucci de Magistris, Maria

AU - Tumino, Rosario

AU - Ricceri, Fulvio

AU - Bueno-de-Mesquita, Bas

AU - Derksen, Jeroen W G

AU - Skeie, Guri

AU - Gram, Inger Torhild

AU - Sandanger, Torkjel

AU - Quirós, J Ramón

AU - Luján-Barroso, Leila

AU - Sánchez, Maria-Jose

AU - Amiano, Pilar

AU - Chirlaque, María-Dolores

AU - Gurrea, Aurelio Barricarte

AU - Johansson, Ingegerd

AU - Manjer, Jonas

AU - Perez-Cornago, Aurora

AU - Weiderpass, Elisabete

AU - Gunter, Marc J

AU - Heath, Alicia K

AU - Schalkwijk, Casper G

AU - Jenab, Mazda

N1 - 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.

PY - 2021/9/8

Y1 - 2021/9/8

N2 - 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 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.

AB - 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 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.

KW - Advanced glycation end-products

KW - Colorectal cancer

KW - Dietary exposure

KW - Dietary glycation compounds

UR - http://www.scopus.com/inward/record.url?scp=85115008015&partnerID=8YFLogxK

U2 - 10.3390/nu13093132

DO - 10.3390/nu13093132

M3 - Article

C2 - 34579010

SN - 2072-6643

VL - 13

JO - Nutrients

JF - Nutrients

IS - 9

M1 - 3132

ER -

Dietary Advanced Glycation End-Products and Colorectal Cancer Risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) Study

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