Data from Circulating RANKL and RANKL/OPG and Breast Cancer Risk by ER and PR Subtype: Results from the EPIC Cohort
Year: 2023
Type: other
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.
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
Language: English
Topic: Cancer Risks and Factors
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
OpenAlex ID: W4392690509