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@ARTICLE{Guan:147458,
author = {Z. Guan$^*$ and J. R. Raut$^*$ and K. Weigl$^*$ and B.
Schöttker$^*$ and B. Holleczek and Y. Zhang$^*$ and H.
Brenner$^*$},
title = {{I}ndividual and joint performance of {DNA} methylation
profiles, genetic risk scores and environmental risk scores
for predicting breast cancer risk.},
journal = {Molecular oncology},
volume = {14},
number = {1},
issn = {1878-0261},
address = {Hoboken, NJ},
publisher = {John Wiley $\&$ Sons, Inc.},
reportid = {DKFZ-2019-02540},
pages = {42-53},
year = {2020},
note = {2020 Jan;14(1):42-53#EA:C070#LA:C070#},
abstract = {DNA methylation patterns in the blood, genetic risk scores
(GRSs) and environmental risk factors can potentially
improve breast cancer (BC) risk prediction. We assessed the
individual and joint predictive performance of methylation,
GRS and environmental risk factors for BC incidence in a
prospective cohort study. In a cohort of 5462 women aged
50-75 from Germany, 101 BC cases were identified during 14
years of follow-up and were compared to 263 BC-free controls
in a nested case-control design. Three previously suggested
methylation risk scores (MRSs) based on methylation of 423,
248 and 131 cytosine-phosphate-guanine (CpG) loci, and a GRS
based on the risk alleles from 269 recently identified
single-nucleotide polymorphisms were constructed.
Additionally, multiple previously proposed environmental
risk scores (ERSs) were built based on environmental
variables. Areas under the receiver operating characteristic
curves (AUCs) were estimated for evaluating BC risk
prediction performance. MRS and ERS showed limited accuracy
in predicting BC incidence, with AUCs ranging from 0.52 to
0.56 and from 0.52 to 0.59, respectively. The GRS predicted
BC incidence with a higher accuracy (AUC=0.61). Adjusted
odds ratios per standard deviation increase $(95\%$
confidence interval) were 1.07 (0.84-1.36) and 1.40
(1.09-1.80) for the best performing MRS and ERS,
respectively, and 1.48 (1.16-1.90) for the GRS. A full risk
model combining the MRS, GRS and ERS predicted BC incidence
with the highest accuracy (AUC=0.64), and might be useful
for identifying high-risk populations for BC screening.},
cin = {C070 / C120 / HD01},
ddc = {610},
cid = {I:(DE-He78)C070-20160331 / I:(DE-He78)C120-20160331 /
I:(DE-He78)HD01-20160331},
pnm = {313 - Cancer risk factors and prevention (POF3-313)},
pid = {G:(DE-HGF)POF3-313},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:31677238},
doi = {10.1002/1878-0261.12594},
url = {https://inrepo02.dkfz.de/record/147458},
}