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Supplementary Tables 1-6 from Circulating RANKL and RANKL/OPG and Breast Cancer Risk by ER and PR Subtype: Results from the EPIC Cohort

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posted on 2023-04-03, 22:04 authored by 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

Supplementary table 1. Correlations of sRANKL and the sRANKL/OPG ratio with select hormones among controls: EPIC cohort nested case-control study. Supplementary table 2. Distribution of covariates by quintiles of sRANKL. Supplementary table 3. Circulating concentrations of sRANKL and breast cancer risk by hormone-receptor subtype and menopausal status at blood collection. Supplementary table 4. The sRANKL/OPG ratio and breast cancer risk by hormone-receptor subtype and menopausal status at blood collection. Supplementary table 5. sRANKL additionally adjusted for continuous (log2) OPG and breast cancer risk by hormone-receptor subtype: EPIC nested case-control study. Supplementary table 6. sRANKL/OPG cross-classification based on median split of sRANKL and OPG and breast cancer risk by hormone-receptor subtype: EPIC nested case-control study.

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Deutsche Kresbshilfe

European Commission's Seventh Framework Programme

Danish Cancer Society

World Cancer Research Fund

Cancer Research UK

Medical Research Council

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ARTICLE 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.

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