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@ARTICLE{Decker:285388,
author = {N. S. Decker$^*$ and T. Johnson$^*$ and J. A. Vey and C. Le
Cornet$^*$ and S. Behrens$^*$ and N. Obi and R. Kaaks$^*$
and J. Chang-Claude$^*$ and R. Turzanski-Fortner$^*$},
title = {{C}irculating oxysterols and prognosis among women with a
breast cancer diagnosis: results from the {MARIE} patient
cohort.},
journal = {BMC medicine},
volume = {21},
number = {1},
issn = {1741-7015},
address = {Heidelberg [u.a.]},
publisher = {Springer},
reportid = {DKFZ-2023-02355},
pages = {438},
year = {2023},
note = {#EA:C020#LA:C020#},
abstract = {Breast cancer is the most commonly diagnosed cancer in
women worldwide, and underlying mechanistic pathways
associated with breast cancer-specific and non-breast
cancer-related deaths are of importance. Emerging evidence
suggests a role of oxysterols, derivates of cholesterol, in
multiple chronic diseases including breast cancer and
coronary artery diseases. However, associations between
oxysterols and survival have been minimally studied in women
diagnosed with breast cancer. In this large breast cancer
patient cohort, we evaluated associations between a panel of
circulating oxysterols and mortality and recurrence
outcomes.Concentrations of 13 circulating oxysterols
representing different pathways of cholesterol metabolism
were quantified using liquid-chromatography
mass-spectrometry. Associations between baseline levels of
oxysterols and cause-specific mortality outcomes and
recurrence following a breast cancer diagnosis were assessed
in 2282 women from the MARIE study over a median follow-up
time of 11 years. We calculated hazard ratios (HR) and
$95\%$ confidence intervals (CI) using multivariable Cox
proportional hazard models and competing risks models.We
observed no associations for circulating oxysterols and
breast cancer-specific outcomes. Higher levels of six
oxysterols were associated with an increased risk of
cardiovascular disease death, including
24S-hydroxycholesterol (alternative bile acid pathway,
HRlog2 = 1.73 (1.02, 2.93)), lanosterol (cholesterol
biosynthesis pathway, HRlog2 = 1.95 (1.34, 2.83)),
7-ketocholesterol (HRlog2 = 1.26 (1.03, 1.55)),
5α,6α-epoxycholesterol (HRlog2 = 1.34 (1.02-1.77)), and
5a,6β-dihydroxycholestanol (HRlog2 = 1.34 (1.03, 1.76)).
After adjusting for multiple comparisons, none of the
associations were statistically significant.We provide first
evidence on a range of circulating oxysterols and mortality
following a breast cancer diagnosis, contributing to a
better understanding of associations between different
pathways of cholesterol metabolism and prognosis in women
with a breast cancer diagnosis. The findings of this study
suggest circulating oxysterols may be associated with
cardiovascular mortality among women diagnosed with breast
cancer. Further studies are needed to evaluate these
oxysterols as potential markers of risk for cardiovascular
mortality among women with a breast cancer diagnosis as well
as their clinical potential.},
keywords = {Breast cancer (Other) / Cancer death (Other) /
Cardiovascular death (Other) / Cholesterol metabolism
(Other) / Cohort study (Other) / Molecular epidemiology
(Other) / Oxysterols (Other) / Survival (Other)},
cin = {C020},
ddc = {610},
cid = {I:(DE-He78)C020-20160331},
pnm = {313 - Krebsrisikofaktoren und Prävention (POF4-313)},
pid = {G:(DE-HGF)POF4-313},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:37964298},
doi = {10.1186/s12916-023-03152-7},
url = {https://inrepo02.dkfz.de/record/285388},
}