Circulating RANKL and RANKL/OPG and Breast Cancer Risk by ER and PR Subtype: Results from the EPIC Cohort
Year: 2017
Type: article
Study design: Observational Study
Abstract: 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. A case–control study was nested in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. This study included 1,976 incident invasive breast cancer cases [estrogen receptor positive (ER+), n = 1,598], matched 1:1 to controls. Women were pre- or postmenopausal at blood collection. Serum sRANKL was quantified using an ELISA, serum OPG using an electrochemiluminescent assay. Risk ratios (RR) and 95% confidence intervals (95% CI) were calculated using conditional logistic regression. 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 [5th vs. 1st quintile RR = 0.60 (0.31–1.14); Ptrend = 0.03]. 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. Cancer Prev Res; 10(9); 525–34. ©2017 AACR.
Source: Cancer Prevention Research
Authors: Danja Sarink, Helena Schock, Theron Johnson, Kim Overvad, Marianne Holm, Anne Tjønneland, Marie-Christine Boutron-Ruault, Mathilde His, Marina Kvaskoff, Heiner Boeing, Pagona Lagiou, Eleni-Maria Papatesta, Antonia Trichopoulou, Domenico Palli, Valeria Pala, Amalia Mattiello, Rosario Tumino, Carlotta Sacerdote, H.B(as). Bueno-de-Mesquita, Carla H. van Gils, Petra H. Peeters, Elisabete Weiderpass, Antonio Agudo, Maria-José Sánchez, Maria-Dolores Chirlaque, Eva Ardanaz, Pilar Amiano, Kay Tee Khaw, Ruth Travis, Laure Dossus, Mark Gunter, Sabina Rinaldi, Melissa Merritt, Elio Riboli, Rudolf Kaaks, Renée T. Fortner
Institutions: German Cancer Research Center, Aarhus University, Danish Cancer Society, Université Paris-Sud, Inserm, Université de Versailles Saint-Quentin-en-Yvelines, Université Paris-Saclay, Institut Gustave Roussy, Centre de recherche en Epidémiologie et Santé des Populations, German Institute of Human Nutrition, Harvard University, National and Kapodistrian University of Athens, Hellenic Health Foundation, Fondazione IRCCS Istituto Nazionale dei Tumori, Federico II University Hospital, University of Naples Federico II, Piedmont Reference Center for Epidemiology and Cancer Prevention, National Institute for Public Health and the Environment, Imperial College London, University Medical Center Utrecht, MRC Centre for Environment and Health, Karolinska Institutet, Cancer Registry of Norway, Folkhälsans Forskningscentrum, UiT The Arctic University of Norway, Institut d'Investigació Biomédica de Bellvitge, Institut Català d'Oncologia, Universidad de Granada, Instituto de Investigación Biosanitaria de Granada, Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública, Andalusian School of Public Health, Instituto Murciano de Investigación Biosanitaria, Universidad de Murcia, Instituto de Salud Pública de Navarra, Navarre Institute of Health Research, Biogipuzkoa Health Research Institute, University of Cambridge, University of Oxford, Centre international de recherche sur le cancer
Language: English
Topic: Cancer Risks and Factors
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: green
Funders: World Health Organization, Deutsches Krebsforschungszentrum, Cancer Research UK, National Institute for Health and Care Research, European Commission, Institut National de la Santé et de la Recherche Médicale, Bundesministerium für Bildung und Forschung, Cancerfonden, Ligue Contre le Cancer, Vetenskapsrådet, NordForsk, Associazione Italiana per la Ricerca sul Cancro, Deutsche Krebshilfe, Institut Gustave-Roussy, Mutuelle Générale de l'Education Nationale, Hellenic Health Foundation, Medical Research Council, World Cancer Research Fund, Instituto de Salud Carlos III
Awards: G1055973116, G1075502044, G1090603134, G1192877484, G1208621354, G1241080153, G1265254713, G1274701479, G1318397260, G1344656563, G1559294051, G172151099, G1767199718, G1788645866, G1907752718, G1952936224, G1993546569, G2131326840, G2149779140, G2149865848, G2216207056, G2235605558, G2257231888, G2336049343, G2372467518, G2409987178, G2539064604, G2561548287, G2572521044, G273148272, G2742323354, G2841678936, G2871896171, G29072894, G2924980845, G3010599472, G3049845011, G3077395769, G3149246560, G3170664214, G3189789075, G3216658785, G331404038, G3452641779, G3461390129, G3544161537, G3675143906, G3747421453, G375319704, G3816092139, G382879149, G385201875, G3980646122, G4012977212, G4015156572, G4041385912, G4049848471, G4081633361, G4089957676, G4213141252, G423622538, G4303038735, G43956866, The RANK-Axis in Breast Cancer: A comprehensive prospective evaluation of promising novel biomarkers, G4473162978, Health of vegetarians, G459595259, G4682079261, G4811780622, G4879533352, G490534113, G4913827001, G5004963360, G5047213743, G5119219000, G5375816427, G5406065712, G5456958854, G5560955959, G5578953934, G558017500, G5651954792, G569447510, G569908600, G5706284561, G5750710683, G5868006920, G5897142711, G5990830295, G6085534252, NIHR Senior Investigator Award, G6212483348, G6264211199, G6320156643, G640002926, G6442500046, G657255654, G6594529311, G6631454880, G6723261869, G6820515600, G6883270616, G6960682749, G7020115967, G7022277044, G7025202487, G7040807446, G7306252069, G7426181285, G7447125227, G7600088736, G7624991799, G7646326732, G7838322234, G7853538257, G7939399614, G8012318887, G8050896463, G817390530, G8279237360, G8331243404, G8374761964, G8407261631, G8508326818, G8525262851, G876765158, G8867963557, G8869854444, G8959392569, G8978728421
OpenAlex ID: W2736033004