TY - JOUR
T1 - Circulating RANKL and RANKL/OPG and Breast Cancer Risk by ER and PR Subtype
T2 - Results from the EPIC Cohort
AU - Sarink, Danja
AU - Schock, Helena
AU - Johnson, Theron
AU - Overvad, Kim
AU - Holm, Marianne
AU - Tjønneland, Anne
AU - Boutron-Ruault, Marie Christine
AU - His, Mathilde
AU - Kvaskoff, Marina
AU - Boeing, Heiner
AU - Lagiou, Pagona
AU - Papatesta, Eleni-Maria
AU - Trichopoulou, Antonia
AU - Palli, Domenico
AU - Pala, Valeria
AU - Mattiello, Amalia
AU - Tumino, Rosario
AU - Sacerdote, Carlotta
AU - Bueno-de-Mesquita, H B As
AU - van Gils, Carla H
AU - Peeters, Petra H
AU - Weiderpass, Elisabete
AU - Agudo, Antonio
AU - Sánchez, Maria-José
AU - Chirlaque, Maria-Dolores
AU - Ardanaz, Eva
AU - Amiano, Pilar
AU - Khaw, Kay Tee
AU - Travis, Ruth C.
AU - Dossus, Laure
AU - Gunter, Mark
AU - Rinaldi, Sabina
AU - Merritt, Melissa A.
AU - Riboli, Elio
AU - Kaaks, Rudolf
AU - Turzanski-Fortner, Renée
N1 - Publisher Copyright:
© 2017 American Association for Cancer Research.
PY - 2017/9
Y1 - 2017/9
N2 - 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) and95% 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); P
trend=0.03]. This study provides the first largescale prospective data on circulating sRANKLand breast cancer. We observed limited evidence for an association between sRANKLand breast cancer risk. Cancer Prev Res; 10(9); 525-34.
AB - 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) and95% 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); P
trend=0.03]. This study provides the first largescale prospective data on circulating sRANKLand breast cancer. We observed limited evidence for an association between sRANKLand breast cancer risk. Cancer Prev Res; 10(9); 525-34.
U2 - 10.1158/1940-6207.CAPR-17-0125
DO - 10.1158/1940-6207.CAPR-17-0125
M3 - Article
C2 - 28701332
SN - 1940-6215
VL - 10
SP - 525
EP - 534
JO - Cancer prevention research (Philadelphia, Pa.)
JF - Cancer prevention research (Philadelphia, Pa.)
IS - 9
ER -