Multicenter Study

. 2021 Jan;30(1):182-192.

doi: 10.1158/1055-9965.EPI-20-0855. Epub 2020 Oct 20.

Soluble Receptor for Advanced Glycation End-products (sRAGE) and Colorectal Cancer Risk: A Case-Control Study Nested within a European Prospective Cohort

Elom K Aglago¹, Sabina Rinaldi¹, Heinz Freisling¹, Li Jiao², David J Hughes³, Veronika Fedirko⁴, Casper G Schalkwijk⁵, Elisabete Weiderpass⁶, Christina C Dahm⁷, Kim Overvad^{7

8}, Anne Kirstine Eriksen⁹, Cecilie Kyrø⁹, Marie-Christine Boutron-Ruault^{10

11}, Joseph A Rothwell^{10

11}, Gianluca Severi^{10

11

12}, Verena Katzke¹³, Tilman Kühn¹³, Matthias B Schulze^{14

15}, Krasimira Aleksandrova^{15

16}, Giovanna Masala¹⁷, Vittorio Krogh¹⁸, Salvatore Panico¹⁹, Rosario Tumino²⁰, Alessio Naccarati^{21

22}, Bas Bueno-de-Mesquita²³, Carla H van Gils²⁴, Torkjel M Sandanger²⁵, Inger T Gram²⁶, Guri Skeie²⁶, J Ramón Quirós²⁷, Paula Jakszyn^{28

29}, Maria-Jose Sánchez^{30

31

32

33}, Pilar Amiano^{32

34}, José María Huerta^{32

35}, Eva Ardanaz^{32

36

37}, Ingegerd Johansson³⁸, Sophia Harlid³⁸, Aurora Perez-Cornago³⁹, Ana-Lucia Mayén¹, Reynalda Cordova¹, Marc J Gunter¹, Paolo Vineis⁴⁰, Amanda J Cross⁴⁰, Elio Riboli⁴⁰, Mazda Jenab⁴¹

Affiliations

¹ Nutrition and Metabolism Section, International Agency for Research on Cancer (IARC), Lyon, France.
² Department of Medicine, Baylor College of Medicine, Houston, Texas.
³ Cancer Biology and Therapeutics Group (CBT), Conway Institute, School of Biomolecular and Biomedical Science (SBBS), University College Dublin, Dublin, Ireland.
⁴ Department of Epidemiology, Rollins School of Public Health, Winship Cancer Institute, Emory University, Atlanta, Georgia.
⁵ Department of Internal Medicine, CARIM School for Cardiovascular Diseases, Maastricht University Medical Center, Maastricht, the Netherlands.
⁶ Office of the Director, International Agency for Research on Cancer (IARC), Lyon, France.
⁷ Department of Public Health, Aarhus University, Aarhus, Denmark.
⁸ Department of Cardiology, Aalborg University Hospital, Aalborg, Denmark.
⁹ Danish Cancer Society Research Center, Copenhagen, Denmark.
¹⁰ CESP, Faculté de Médecine - Université Paris-Saclay, UVSQ, INSERM, Villejuif, Paris, France.
¹¹ Gustave Roussy, Villejuif, Paris, France.
¹² Department of Statistics, Computer Science and Applications (DISIA), University of Florence, Florence, Italy.
¹³ German Cancer Research Center (DKFZ), Foundation under Public Law, Heidelberg, Germany.
¹⁴ Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany.
¹⁵ Institute of Nutrition Science, University of Potsdam, Nuthetal, Germany.
¹⁶ Nutrition, Immunity and Metabolism Senior Scientist Group, Department of Nutrition and Gerontology, German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Nuthetal, Germany.
¹⁷ Cancer Risk Factors and Life-Style Epidemiology Unit, Institute for Cancer Research, Prevention and Clinical Network - ISPRO, Florence, Italy.
¹⁸ Epidemiology and Prevention Unit, Department of Research, Fondazione IRCCS Istituto Nazionale dei Tumori Via Venezian, Milano, Italy.
¹⁹ Dipartimento di Medicina Clinica e Chirurgia Federico II University, Naples, Italy.
²⁰ Department of Cancer Registry and Histopathology, Provincial Health Authority (ASP), Ragusa, Italy.
²¹ Italian Institute for Genomic Medicine (IIGM), c/o IRCCS Candiolo, Candiolo, Torino, Italy.
²² Candiolo Cancer Institute, FPO-IRCCS, Candiolo, Torino, Italy.
²³ Department for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands.
²⁴ University Medical Center Utrecht, Utrecht, the Netherlands.
²⁵ Faculty of Health Sciences, Department of Community Medicine, UiT-The Arctic University of Norway, Tromsø, Norway.
²⁶ Faculty of Health Sciences, Department of Community Medicine, University of Tromsø, The Arctic University of Norway, Tromsø, Norway.
²⁷ Public Health Directorate, Oviedo, Spain.
²⁸ Unit of Nutrition and Cancer, Cancer Epidemiology Research Programme, Catalan Institute of Oncology (ICO-IDIBELL), Barcelona, Spain.
²⁹ Blanquerna School of Health Sciences, Ramon Llull University, Barcelona, Spain.
³⁰ Escuela Andaluza de Salud Pública (EASP), Granada, Spain.
³¹ Instituto de Investigación Biosanitaria ibs.GRANADA, Granada, Spain.
³² Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain.
³³ Department of Preventive Medicine and Public Health, University of Granada, Granada, Spain.
³⁴ Public Health Division of Gipuzkoa, BioDonostia Research Institute, Donostia-San Sebastian, Spain.
³⁵ Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca, Murcia, Spain.
³⁶ Navarra Public Health Institute, Pamplona, Spain.
³⁷ IdiSNA, Navarra Institute for Health Research, Pamplona, Spain.
³⁸ Department of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden.
³⁹ Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, England, United Kingdom.
⁴⁰ School of Public Health, Imperial College London, London, England, United Kingdom.
⁴¹ Nutrition and Metabolism Section, International Agency for Research on Cancer (IARC), Lyon, France. jenabm@iarc.fr.

PMID: 33082206
DOI: 10.1158/1055-9965.EPI-20-0855

Multicenter Study

Soluble Receptor for Advanced Glycation End-products (sRAGE) and Colorectal Cancer Risk: A Case-Control Study Nested within a European Prospective Cohort

Elom K Aglago et al. Cancer Epidemiol Biomarkers Prev. 2021 Jan.

. 2021 Jan;30(1):182-192.

doi: 10.1158/1055-9965.EPI-20-0855. Epub 2020 Oct 20.

Authors

Affiliations

¹ Nutrition and Metabolism Section, International Agency for Research on Cancer (IARC), Lyon, France.
² Department of Medicine, Baylor College of Medicine, Houston, Texas.
³ Cancer Biology and Therapeutics Group (CBT), Conway Institute, School of Biomolecular and Biomedical Science (SBBS), University College Dublin, Dublin, Ireland.
⁴ Department of Epidemiology, Rollins School of Public Health, Winship Cancer Institute, Emory University, Atlanta, Georgia.
⁵ Department of Internal Medicine, CARIM School for Cardiovascular Diseases, Maastricht University Medical Center, Maastricht, the Netherlands.
⁶ Office of the Director, International Agency for Research on Cancer (IARC), Lyon, France.
⁷ Department of Public Health, Aarhus University, Aarhus, Denmark.
⁸ Department of Cardiology, Aalborg University Hospital, Aalborg, Denmark.
⁹ Danish Cancer Society Research Center, Copenhagen, Denmark.
¹⁰ CESP, Faculté de Médecine - Université Paris-Saclay, UVSQ, INSERM, Villejuif, Paris, France.
¹¹ Gustave Roussy, Villejuif, Paris, France.
¹² Department of Statistics, Computer Science and Applications (DISIA), University of Florence, Florence, Italy.
¹³ German Cancer Research Center (DKFZ), Foundation under Public Law, Heidelberg, Germany.
¹⁴ Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany.
¹⁵ Institute of Nutrition Science, University of Potsdam, Nuthetal, Germany.
¹⁶ Nutrition, Immunity and Metabolism Senior Scientist Group, Department of Nutrition and Gerontology, German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Nuthetal, Germany.
¹⁷ Cancer Risk Factors and Life-Style Epidemiology Unit, Institute for Cancer Research, Prevention and Clinical Network - ISPRO, Florence, Italy.
¹⁸ Epidemiology and Prevention Unit, Department of Research, Fondazione IRCCS Istituto Nazionale dei Tumori Via Venezian, Milano, Italy.
¹⁹ Dipartimento di Medicina Clinica e Chirurgia Federico II University, Naples, Italy.
²⁰ Department of Cancer Registry and Histopathology, Provincial Health Authority (ASP), Ragusa, Italy.
²¹ Italian Institute for Genomic Medicine (IIGM), c/o IRCCS Candiolo, Candiolo, Torino, Italy.
²² Candiolo Cancer Institute, FPO-IRCCS, Candiolo, Torino, Italy.
²³ Department for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands.
²⁴ University Medical Center Utrecht, Utrecht, the Netherlands.
²⁵ Faculty of Health Sciences, Department of Community Medicine, UiT-The Arctic University of Norway, Tromsø, Norway.
²⁶ Faculty of Health Sciences, Department of Community Medicine, University of Tromsø, The Arctic University of Norway, Tromsø, Norway.
²⁷ Public Health Directorate, Oviedo, Spain.
²⁸ Unit of Nutrition and Cancer, Cancer Epidemiology Research Programme, Catalan Institute of Oncology (ICO-IDIBELL), Barcelona, Spain.
²⁹ Blanquerna School of Health Sciences, Ramon Llull University, Barcelona, Spain.
³⁰ Escuela Andaluza de Salud Pública (EASP), Granada, Spain.
³¹ Instituto de Investigación Biosanitaria ibs.GRANADA, Granada, Spain.
³² Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain.
³³ Department of Preventive Medicine and Public Health, University of Granada, Granada, Spain.
³⁴ Public Health Division of Gipuzkoa, BioDonostia Research Institute, Donostia-San Sebastian, Spain.
³⁵ Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca, Murcia, Spain.
³⁶ Navarra Public Health Institute, Pamplona, Spain.
³⁷ IdiSNA, Navarra Institute for Health Research, Pamplona, Spain.
³⁸ Department of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden.
³⁹ Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, England, United Kingdom.
⁴⁰ School of Public Health, Imperial College London, London, England, United Kingdom.
⁴¹ Nutrition and Metabolism Section, International Agency for Research on Cancer (IARC), Lyon, France. jenabm@iarc.fr.

PMID: 33082206
DOI: 10.1158/1055-9965.EPI-20-0855

Abstract

Background: Overexpression of the receptor for advanced glycation end-product (RAGE) has been associated with chronic inflammation, which in turn has been associated with increased colorectal cancer risk. Soluble RAGE (sRAGE) competes with RAGE to bind its ligands, thus potentially preventing RAGE-induced inflammation.

Methods: To investigate whether sRAGE and related genetic variants are associated with colorectal cancer risk, we conducted a nested case-control study in the European Prospective Investigation into Cancer and Nutrition (EPIC). Plasma sRAGE concentrations were measured by ELISA in 1,361 colorectal cancer matched case-control sets. Twenty-four SNPs encoded in the genes associated with sRAGE concentrations were available for 1,985 colorectal cancer cases and 2,220 controls. Multivariable adjusted ORs and 95% confidence intervals (CIs) were computed using conditional and unconditional logistic regression for colorectal cancer risk and circulating sRAGE and SNPs, respectively.

Results: Higher sRAGE concentrations were inversely associated with colorectal cancer (OR_Q5vs.Q1, 0.77; 95% CI, 0.59-1.00). Sex-specific analyses revealed that the observed inverse risk association was restricted to men (OR_Q5vs.Q1, 0.63; 95% CI, 0.42-0.94), whereas no association was observed in women (OR_Q5vs.Q1, 1.00; 95% CI, 0.68-1.48; P _{heterogeneity} for sex = 0.006). Participants carrying minor allele of rs653765 (promoter region of ADAM10) had lower colorectal cancer risk (C vs. T, OR, 0.90; 95% CI, 0.82-0.99).

Conclusions: Prediagnostic sRAGE concentrations were inversely associated with colorectal cancer risk in men, but not in women. An SNP located within ADAM10 gene, pertaining to RAGE shedding, was associated with colorectal cancer risk.

Impact: Further studies are needed to confirm our observed sex difference in the association and better explore the potential involvement of genetic variants of sRAGE in colorectal cancer development.

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Soluble Receptor for Advanced Glycation End-products (sRAGE) and Colorectal Cancer Risk: A Case-Control Study Nested within a European Prospective Cohort

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Soluble Receptor for Advanced Glycation End-products (sRAGE) and Colorectal Cancer Risk: A Case-Control Study Nested within a European Prospective Cohort

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