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@ARTICLE{Sarink:141336,
author = {D. Sarink$^*$ and H. Schock$^*$ and T. S. Johnson$^*$ and
J. Chang-Claude$^*$ and K. Overvad and A. Olsen and A.
Tjønneland and P. Arveux and A. Fournier and M. Kvaskoff
and H. Boeing and A. Karakatsani and A. Trichopoulou and C.
La Vecchia and G. Masala and C. Agnoli and S. Panico and R.
Tumino and C. Sacerdote and C. H. van Gils and P. H. M.
Peeters and E. Weiderpass and A. Agudo and M.
Rodríguez-Barranco and J. M. Huerta and E. Ardanaz and L.
Gil and K. T. Kaw and J. A. Schmidt and L. Dossus and M. His
and D. Aune and E. Riboli and R. Kaaks$^*$ and R.
Turzanski-Fortner$^*$},
title = {{R}eceptor activator of nuclear factor k{B} ligand,
osteoprotegerin, and risk of death following a breast cancer
diagnosis: results from the {EPIC} cohort.},
journal = {BMC cancer},
volume = {18},
number = {1},
issn = {1471-2407},
address = {Heidelberg},
publisher = {Springer},
reportid = {DKFZ-2018-01855},
pages = {1010},
year = {2018},
abstract = {Receptor activator of nuclear factor kappa-B
(RANK)-signaling is involved in tumor growth and spread in
experimental models. Binding of RANK ligand (RANKL) to RANK
activates signaling, which is inhibited by osteoprotegerin
(OPG). We have previously shown that circulating soluble
RANKL (sRANKL) and OPG are associated with breast cancer
risk. Here we extend these findings to provide the first
data on pre-diagnosis concentrations of sRANKL and OPG and
risk of breast cancer-specific and overall mortality after
a breast cancer diagnosis.Two thousand six pre- and
postmenopausal women with incident invasive breast cancer
(1620 $(81\%)$ with ER+ disease) participating in the
European Prospective Investigation into Cancer and Nutrition
(EPIC) cohort were followed-up for mortality. Pre-diagnosis
concentrations of sRANKL and OPG were quantified in baseline
serum samples using an enzyme-linked immunosorbent assay and
electrochemiluminescent assay, respectively. Hazard ratios
(HRs) and $95\%$ confidence intervals (CIs) for breast
cancer-specific and overall mortality were calculated using
Cox proportional hazards regression models.Especially in
women with ER+ disease, higher circulating OPG
concentrations were associated with higher risk of breast
cancer-specific (quintile 5 vs 1 HR 1.77 [CI 1.03, 3.04];
ptrend 0.10) and overall mortality (q5 vs 1 HR 1.39 [CI
0.94, 2.05]; ptrend 0.02). sRANKL and the sRANKL/OPG ratio
were not associated with mortality following a breast cancer
diagnosis.High pre-diagnosis endogenous concentrations of
OPG, the decoy receptor for RANKL, were associated with
increased risk of death after a breast cancer diagnosis,
especially in those with ER+ disease. These results need to
be confirmed in well-characterized patient cohorts.},
cin = {C020},
ddc = {610},
cid = {I:(DE-He78)C020-20160331},
pnm = {313 - Cancer risk factors and prevention (POF3-313)},
pid = {G:(DE-HGF)POF3-313},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:30348163},
pmc = {pmc:PMC6196438},
doi = {10.1186/s12885-018-4887-3},
url = {https://inrepo02.dkfz.de/record/141336},
}