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) 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); Ptrend=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.
| Original language | English |
|---|---|
| Pages (from-to) | 525-534 |
| Number of pages | 10 |
| Journal | Cancer Prevention Research |
| Volume | 10 |
| Issue number | 9 |
| DOIs | |
| Publication status | Published - Sep 1 2017 |
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ASJC Scopus subject areas
- Oncology
- Cancer Research
Cite this
Circulating RANKL and RANKL/OPG and breast cancer risk by ER and PR subtype : Results from the EPIC cohort. / Sarink, Danja; Schock, Helena; Johnson, Theron; Overvad, Kim; Holm, Marianne; Tjønneland, Anne; Boutron-Ruault, Marie Christine; His, Mathilde; Kvaskoff, Marina; Boeing, Heiner; Lagiou, Pagona; Papatesta, Eleni Maria; Trichopoulou, Antonia; Palli, Domenico; Pala, Valeria; Mattiello, Amalia; Tumino, Rosario; Sacerdote, Carlotta; Bueno-De-Mesquita, H. B.; Van Gils, Carla H.; Peeters, Petra H.; Weiderpass, Elisabete; Agudo, Antonio; Sánchez, Maria José; Chirlaque, Maria Dolores; Ardanaz, Eva; Amiano, Pilar; Khaw, Kay Tee; Travis, Ruth; Dossus, Laure; Gunter, Mark; Rinaldi, Sabina; Merritt, Melissa; Riboli, Elio; Kaaks, Rudolf; Fortner, Renée T.
In: Cancer Prevention Research, Vol. 10, No. 9, 01.09.2017, p. 525-534.Research output: Contribution to journal › Article
}
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.
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
AU - Dossus, Laure
AU - Gunter, Mark
AU - Rinaldi, Sabina
AU - Merritt, Melissa
AU - Riboli, Elio
AU - Kaaks, Rudolf
AU - Fortner, Renée T.
PY - 2017/9/1
Y1 - 2017/9/1
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); Ptrend=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); Ptrend=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.
UR - http://www.scopus.com/inward/record.url?scp=85029542301&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85029542301&partnerID=8YFLogxK
U2 - 10.1158/1940-6207.CAPR-17-0125
DO - 10.1158/1940-6207.CAPR-17-0125
M3 - Article
AN - SCOPUS:85029542301
VL - 10
SP - 525
EP - 534
JO - Cancer Prevention Research
JF - Cancer Prevention Research
SN - 1940-6207
IS - 9
ER -