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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  • Elom Kouassivi Aglago, WHO International Agency for Research on Cancer, Frankrig
  • Sabina Rinaldi, WHO International Agency for Research on Cancer, Frankrig
  • Heinz Freisling, WHO International Agency for Research on Cancer, Frankrig
  • Li Jiao, Department of Medicine, Baylor College of Medicine, USA
  • David J Hughes, University College Dublin, Dublin, Irland
  • Veronika Fedirko, Emory University, USA
  • Casper G Schalkwijk, Maastricht University Medical Center, Holland
  • Elisabete Weiderpass, WHO International Agency for Research on Cancer, Frankrig
  • Christina C Dahm
  • Kim Overvad
  • Anne Kirstine Eriksen, Danish Cancer Society Research Center, The Danish Cancer Society, Copenhagen, Danmark
  • Cecilie Kyrø, Danish Cancer Society Research Center, The Danish Cancer Society, Copenhagen, Danmark
  • Marie-Christine Boutron-Ruault, Exposome and Heredity Team, Universite Paris-Sud, UVSQ, CESP, INSERM, Frankrig
  • Joseph A Rothwell, Health across Generations Team, Inserm U1018, Gustave Roussy., Frankrig
  • Gianluca Severi, Université de Bordeaux, ISPED, Centre INSERM U897, Bordeaux, France; INSERM, Centre INSERM U897, Bordeaux, France., Frankrig
  • Verena Katzke, German Cancer Research Center, Tyskland
  • Tilman Kühn, German Cancer Research Center, Tyskland
  • Matthias B Schulze, German Institute of Human Nutrition Potsdam-Rehbruecke, Potsdam, Germany., Tyskland
  • Krasimira Aleksandrova, German Institute of Human Nutrition Potsdam-Rehbruecke, Potsdam, Germany., Tyskland
  • Giovanna Masala, Institute for Cancer Research, Italien
  • Vittorio Krogh, Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Italien
  • Salvatore Panico, Department of Clinical Medicine and Surgery, Unit of Clinical Epidemiology and Predictive Medicine, Federico II University, Italien
  • Rosario Tumino, Cancer Registry and Histopathology Unit, ASP 7, Ragusa, Italy AIRE-ONLUS - Ragusa, Ragusa, Italy., Italien
  • Alessio Naccarati, Italian Institute for Genomic Medicine, Turin, Italy., Italien
  • Bas Bueno-de-Mesquita, National Institute for Public Health and the Environment, Bilthoven, Netherlands., Holland
  • Carla H van Gils, University Medical Center, Utrecht, Holland
  • Torkjel M Sandanger, UiT—The Arctic University of Norway, Norge
  • Inger T Gram, University of Tromsø, Tromsø, Norge
  • Guri Skeie, UiT - The Arctic University of Norway, Tromsø Museum, Tromsø, Norway., Norge
  • J Ramón Quirós, Public Health and Health Planning Directorate, Spanien
  • Paula Jakszyn, Catalan Institute of Oncology, Barcelona, Spanien
  • Maria-Jose Sánchez, Escuela Andaluza de Salud Pública, Instituto de Investigación Biosanitaria ibs.GRANADA, Hospitales Universitarios de Granada/Universidad de Granada, Av. del Hospicio, s/n, 18010 Granada, Spain., Spanien
  • Pilar Amiano, Biodonostia Health Research Institute, Spanien
  • José María Huerta, Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca, Murcia, Spain; CIBER de Epidemiología y Salud Pública (CIBERESP), Spain., Spanien
  • Eva Ardanaz, Navarra Public Health Institute, Spanien
  • Ingegerd Johansson, University of Umeå, Umeå, Sweden., Sverige
  • Sophia Harlid, University of Umeå, Umeå, Sweden., Sverige
  • Aurora Perez-Cornago, University of Oxford, Oxford, Storbritannien
  • Ana-Lucia Mayén, WHO International Agency for Research on Cancer, Frankrig
  • Reynalda Cordova, WHO International Agency for Research on Cancer, Frankrig
  • Marc J Gunter, WHO International Agency for Research on Cancer
  • ,
  • Paolo Vineis, Imperial College, Storbritannien
  • Amanda J Cross, Imperial College, Storbritannien
  • Elio Riboli, Imperial College, Storbritannien
  • Mazda Jenab, Section of Nutrition and Metabolism, International Agency for Research on Cancer (IARC-WHO), Lyon, France. jenabm@iarc.fr., Frankrig

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 (CRC) 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 CRC 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 CRC matched case-control sets. Twenty-four single nucleotide polymorphisms (SNPs) encoded in the genes associated with sRAGE concentrations were available for 1,985 CRC cases and 2,220 controls. Multivariable-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were computed using conditional and unconditional logistic regression for CRC risk and circulating sRAGE and SNPs, respectively.

RESULTS: Higher sRAGE concentrations were inversely associated with CRC (ORQ5vs.Q1=0.77, 95%CI=0.59-1.00). Sex-specific analyses revealed that the observed inverse risk association was restricted to men (ORQ5vs.Q1=0.63, 95%CI=0.42-0.94) whereas no association was observed in women (ORQ5vs.Q1=1.00, 95%CI=0.68-1.48, Pheterogeneity for sex=0.006). Participants carrying minor allele of rs653765 (promoter region of ADAM10) had lower CRC risk (C vs. T, OR=0.90; 95%CI=0.82-0.99).

CONCLUSIONS: Pre-diagnostic sRAGE concentrations were inversely associated with CRC risk in men but not in women. A SNP located within ADAM10 gene pertaining to RAGE shedding, was associated with CRC 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 CRC development.

OriginalsprogEngelsk
TidsskriftCancer Epidemiology, Biomarkers & Prevention
Vol/bind30
Nummer1
Sider (fra-til)182-192
Antal sider11
ISSN1055-9965
DOI
StatusUdgivet - jan. 2021

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Copyright ©2020, American Association for Cancer Research.

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