Circulating RANKL and RANKL/OPG and breast cancer risk by ER and PR subtype: Results from the EPIC cohort

Publikation: Forskning - peer reviewTidsskriftartikel


  • Danja Sarink
    Danja SarinkDivision of Cancer Epidemiology, German Cancer Research Center (DKFZ).Tyskland
  • Helena Schock
    Helena SchockDivision of Cancer Epidemiology, German Cancer Research Center (DKFZ).Tyskland
  • Theron Johnson
    Theron JohnsonDivision of Cancer Epidemiology, German Cancer Research Center (DKFZ).Tyskland
  • Kim Overvad
  • Marianne Holm
    Marianne HolmDiet, Genes and Environment Unit, Danish Cancer Society Research Center, Copenhagen, Denmark.Danmark
  • Anne Tjonneland
    Anne TjonnelandDiet, Genes and Environment Unit, Danish Cancer Society Research Center, Copenhagen, Denmark.Danmark
  • Marie-Christine Boutron-Ruault
    Marie-Christine Boutron-RuaultUniversité Paris-Saclay, Université Paris-Sud, UVSQ, CESP, INSERM UMRS 1018, Villejuif F-94805, France.Frankrig
  • Mathilde His
    Mathilde HisInstitut Gustave-RoussyFrankrig
  • Marina Kvaskoff
    Marina KvaskoffInstitut Gustave-RoussyFrankrig
  • Heiner Boeing
    Heiner BoeingDepartment of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke.Tyskland
  • Pagona Lagiou
    Pagona LagiouDepartment of Epidemiology, Harvard School of Public Health, Boston, MassachusettsUSA
  • Eleni-Maria Papatesta
    Eleni-Maria PapatestaHellenic Health Foundation.Grækenland
  • Antonia Trichopoulou
    Antonia TrichopoulouWHO Collaborating Center for Nutrition and Health, Unit of Nutritional Epidemiology and Nutrition in Public Health, Department of Hygiene, Epidemiology, and Medical Statistics, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.Grækenland
  • Domenico Palli
    Domenico PalliCancer Risk Factors and Lifestyle Epidemiology Unit, Cancer Research and Prevention Institute (ISPO), Florence, Italy.Italien
  • Valeria Pala
    Valeria PalaEpidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei TumoriItalien
  • Amalia Mattiello
    Amalia MattielloDipartimento di Medicina Clinica e Chirurgia, Federico II University, Naples, Italy.Italien
  • Rosario Tumino
    Rosario TuminoCancer Registry and Histopathology Unit, "Civic-M.P.Arezzo" Hospital, ASP, Via Dante N° 109, 97100 Ragusa, Italy.Italien
  • Carlotta Sacerdote
    Carlotta SacerdoteUnit of Cancer Epidemiology, Città della Salute e della Scienza University-Hospital and Center for Cancer Prevention (CPO), Turin, Italy.Italien
  • Hb As Bueno-de-Mesquita
    Hb As Bueno-de-MesquitaDepartment for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands.Holland
  • Carla H van Gils
    Carla H van GilsJulius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands.Holland
  • Petra H Peeters
    Petra H PeetersDepartment of Epidemiology and Biostatistics, MRC-PHE Centre for Environment and Health, The School of Public Health, Imperial College, W2 1NY London, UK.Storbritannien
  • Elisabete Weiderpass
    Elisabete WeiderpassDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, Solna, SwedenSverige
  • Antonio Agudo
    Antonio AgudoUnit of Nutrition and Cancer. Cancer Epidemiology Research Program. Catalan Institute of Oncology-IDIBELL. L'Hospitalet de Llobregat, Barcelona, Spain.Spanien
  • María-José Sánchez
    María-José SánchezCIBER Epidemiologia y Salud Publica (CIBERESP).Spanien
  • Maria-Dolores Chirlaque
    Maria-Dolores ChirlaqueDepartment of Health and Social Sciences, Universidad Catolica San Antonio de Murcia.Spanien
  • Eva Ardanaz
    Eva ArdanazEpidemiology, Prevention and Promotion Health Service, Institute of Public Health Navarra, Pamplona, Navarra, SpainSpanien
  • Pilar Amiano
    Pilar AmianoPublic Health Division of Gipuzkoa, Basque Government, Spain; Health Research Institute, Biodonostia, San Sebastián, Spain.Spanien
  • Kay-Tee Khaw
    Kay-Tee KhawCancer Epidemiology Unit, University of Cambridge, Cambridge, UK.Storbritannien
  • Ruth C Travis
    Ruth C TravisCancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK.Storbritannien
  • Laure Dossus
    Laure DossusInternational Agency for Research on CancerFrankrig
  • Marc J Gunter
    Marc J GunterInternational Agency for Research on CancerFrankrig
  • Sabina Rinaldi
    Sabina RinaldiInternational Agency for Research on CancerFrankrig
  • Melissa A Merritt
    Melissa A MerrittDepartment of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, U.K.Storbritannien
  • Elio Riboli
    Elio RiboliDepartment of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, U.K.Storbritannien
  • Rudolf Kaaks
    Rudolf KaaksDivision of Cancer Epidemiology, German Cancer Research Center (DKFZ).Tyskland
  • Renée T Fortner
    Renée T FortnerDivision of Cancer Epidemiology, German Cancer Research Center (DKFZ)

Receptor activator of nuclear factor kappa-B (RANK)-RANK ligand (RANKL) signaling promotes mammary tumor development in experimental models. Circulating concentrations of soluble RANKL (sRANKL) may influence breast cancer risk via activation of RANK signaling; this may be modulated by osteoprotegerin (OPG), the decoy receptor for RANKL. sRANKL and breast cancer risk by hormone receptor subtype has not previously been investigated. <p>A case-control study was nested in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. This study included 1976 incident invasive breast cancer cases (estrogen receptor positive (ER+), n=1598), matched 1:1 to controls. Women were pre- or postmenopausal at blood collection. Serum sRANKL was quantified using an enzyme-linked immunosorbent assay, serum OPG using an electrochemiluminescent assay. Risk ratios (RRs) and 95% confidence intervals (95%CIs) were calculated using conditional logistic regression.</p> <p>Associations between sRANKL and breast cancer risk differed by tumor hormone receptor status (phet 0.05). Higher concentrations of sRANKL were positively associated with risk of ER+ breast cancer (5th vs. 1st quintile RR 1.28 [95%CI 1.01-1.63]; ptrend 0.20), but not ER- disease. For both ER+ and estrogen and progesterone receptor positive (ER+PR+) breast cancer, results considering the sRANKL/OPG ratio were similar to those for sRANKL; we observed a suggestive inverse association between the ratio and ER-PR- disease (5(th) vs. 1(st) quintile RR 0.60 [0.31-1.14]; ptrend 0.03).</p> <p>This study provides the first large-scale prospective data on circulating sRANKL and breast cancer. We observed limited evidence for an association between sRANKL and breast cancer risk.

TidsskriftCancer Prevention Research
Sider (fra-til)525-534
Antal sider10
StatusUdgivet - sep. 2017

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