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@ARTICLE{Jaskulski:141420,
author = {S. Jaskulski$^*$ and A. Y. Jung$^*$ and S. Behrens$^*$ and
T. S. Johnson$^*$ and R. Kaaks$^*$ and K. Thöne and D.
Flesch-Janys and D. Sookthai$^*$ and J. Chang-Claude$^*$},
title = {{C}irculating enterolactone concentrations and prognosis of
postmenopausal breast cancer: assessment of mediation by
inflammatory markers.},
journal = {International journal of cancer},
volume = {143},
number = {11},
issn = {0020-7136},
address = {Bognor Regis},
publisher = {Wiley-Liss},
reportid = {DKFZ-2018-01926},
pages = {2698 - 2708},
year = {2018},
abstract = {Higher lignan exposure has been associated with lower
all-cause mortality (ACM) and breast cancer-specific
mortality (BCSM) for postmenopausal breast cancer patients.
However, the biological mechanisms underpinning these
associations are still unclear. We investigated for the
first time whether and to what extent the association
between enterolactone (ENL), the major lignan metabolite,
and postmenopausal breast cancer prognosis is mediated by
inflammatory biomarkers. Circulating concentrations of ENL
and inflammatory markers were measured in a population-based
prospective cohort of 1,743 breast cancer patients recruited
between 2002 and 2005 and followed-up until 2009. Hazard
ratios (HR) and $95\%$ CIs were estimated using
multivariable Cox regression. Mediation analysis was
performed to estimate the percentage association between ENL
(log2) and ACM, BCSM and distant disease-free survival
(DDFS), which is mediated by C-reactive protein (CRP)
(log2), as the strongest potential mediator, and also
interleukin (IL)-10. Median serum/plasma ENL and CRP
concentrations for all patients, including 180 deceased
patients, were 23.2 and 17.5 nmol/L, and 3.2 and 6.5 mg/l,
respectively. ENL concentrations were significantly
inversely associated with ACM, BCSM and DDFS (per doubling
of ENL concentrations: HRs 0.93 [0.87, 0.99], 0.91 [0.84,
0.99] and 0.92 [0.87, 0.99]), after adjusting for prognostic
factors and BMI. Estimated 18, 14 and $12\%$ of the effects
of ENL on ACM, BCSM and DDFS, respectively, were mediated
through CRP. No mediational effect of IL-10 was found. We
provide first evidence that the proinflammatory marker CRP
may partially mediate the association of ENL with
postmenopausal breast cancer survival, which supports
hormone-independent mechanisms.},
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:29974464},
doi = {10.1002/ijc.31647},
url = {https://inrepo02.dkfz.de/record/141420},
}