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@ARTICLE{Baxter:169291,
author = {J. S. Baxter and N. Johnson and K. Tomczyk and A. Gillespie
and S. Maguire and R. Brough and L. Fachal and K.
Michailidou and M. K. Bolla and Q. Wang and J. Dennis and T.
U. Ahearn and I. L. Andrulis and H. Anton-Culver and N. N.
Antonenkova and V. Arndt$^*$ and K. J. Aronson and A.
Augustinsson and H. Becher and M. W. Beckmann and S.
Behrens$^*$ and J. Benitez and M. Bermisheva and N. V.
Bogdanova and S. E. Bojesen and H. Brenner$^*$ and S. Y.
Brucker and Q. Cai and D. Campa$^*$ and F. Canzian$^*$ and
J. E. Castelao and T. L. Chan and J. Chang-Claude$^*$ and S.
J. Chanock and G. Chenevix-Trench and J.-Y. Choi and C. L.
Clarke and S. Colonna and D. M. Conroy and F. J. Couch and
A. Cox and S. S. Cross and K. Czene and M. B. Daly and P.
Devilee and T. Dörk and L. Dossus and M. Dwek and D. M.
Eccles and A. B. Ekici and A. H. Eliassen and C. Engel and
P. A. Fasching and J. Figueroa and H. Flyger and M.
Gago-Dominguez and C. Gao and M. García-Closas and J. A.
García-Sáenz and M. Ghoussaini and G. G. Giles and M. S.
Goldberg and A. González-Neira and P. Guénel and M.
Gündert$^*$ and L. Haeberle and E. Hahnen and C. A. Haiman
and P. Hall and U. Hamann$^*$ and M. Hartman and S. Hatse
and J. Hauke and A. Hollestelle and R. Hoppe and J. L.
Hopper and M.-F. Hou and H. Ito and M. Iwasaki and A. Jager
and A. Jakubowska and W. Janni and E. M. John and V. Joseph
and A. Jung$^*$ and R. Kaaks$^*$ and D. Kang and R. Keeman
and E. Khusnutdinova and S.-W. Kim and V.-M. Kosma and P.
Kraft and V. N. Kristensen and K. Kubelka-Sabit and A. W.
Kurian and A. Kwong and J. V. Lacey and D. Lambrechts and N.
L. Larson and S. C. Larsson and L. Le Marchand and F.
Lejbkowicz and J. Li and J. Long and A. Lophatananon and J.
Lubiński and A. Mannermaa and M. Manoochehri$^*$ and S.
Manoukian and S. Margolin and K. Matsuo and D. Mavroudis and
R. Mayes and U. Menon and R. L. Milne and N. A. Mohd Taib
and K. Muir and T. A. Muranen and R. A. Murphy and H.
Nevanlinna and K. M. O'Brien and K. Offit and J. E. Olson
and H. Olsson and S. K. Park and T.-W. Park-Simon and A. V.
Patel and P. Peterlongo and J. Peto and D.
Plaseska-Karanfilska and N. Presneau and K. Pylkäs and B.
Rack and G. Rennert and A. Romero and M. Ruebner and T.
Rüdiger and E. Saloustros and D. P. Sandler and E. J.
Sawyer and M. K. Schmidt and R. K. Schmutzler and A.
Schneeweiss and M. J. Schoemaker and M. Shah and C.-Y. Shen
and X.-O. Shu and J. Simard and M. C. Southey and J. Stone
and H. Surowy$^*$ and A. J. Swerdlow and R. M. Tamimi and W.
J. Tapper and J. A. Taylor and S. H. Teo and L. R. Teras and
M. B. Terry and A. E. Toland and I. Tomlinson and T. Truong
and C.-C. Tseng and M. Untch and C. M. Vachon and A. M. W.
van den Ouweland and S. S. Wang and C. R. Weinberg and C.
Wendt and S. J. Winham and R. Winqvist and A. Wolk and A. H.
Wu and T. Yamaji and W. Zheng and A. Ziogas and P. D. P.
Pharoah and A. M. Dunning and D. F. Easton and S. J. Pettitt
and C. J. Lord and S. Haider and N. Orr and O. Fletcher},
collaboration = {NBCS Collaborators and k. Investigators and A.
Investigators},
title = {{F}unctional annotation of the 2q35 breast cancer risk
locus implicates a structural variant in influencing
activity of a long-range enhancer element.},
journal = {The American journal of human genetics},
volume = {108},
number = {7},
issn = {0002-9297},
address = {New York, NY},
publisher = {Elsevier},
reportid = {DKFZ-2021-01388},
pages = {1190-1203},
year = {2021},
note = {2021 Jul 1;108(7):1190-1203},
abstract = {A combination of genetic and functional approaches has
identified three independent breast cancer risk loci at
2q35. A recent fine-scale mapping analysis to refine these
associations resulted in 1 (signal 1), 5 (signal 2), and 42
(signal 3) credible causal variants at these loci. We used
publicly available in silico DNase I and ChIP-seq data with
in vitro reporter gene and CRISPR assays to annotate
signals 2 and 3. We identified putative regulatory elements
that enhanced cell-type-specific transcription from the
IGFBP5 promoter at both signals (30- to 40-fold increased
expression by the putative regulatory element at signal 2,
2- to 3-fold by the putative regulatory element at signal
3). We further identified one of the five credible causal
variants at signal 2, a 1.4 kb deletion (esv3594306), as the
likely causal variant; the deletion allele of this variant
was associated with an average additional increase in IGFBP5
expression of 1.3-fold (MCF-7) and 2.2-fold (T-47D). We
propose a model in which the deletion allele of esv3594306
juxtaposes two transcription factor binding regions
(annotated by estrogen receptor alpha ChIP-seq peaks) to
generate a single extended regulatory element. This
regulatory element increases cell-type-specific expression
of the tumor suppressor gene IGFBP5 and, thereby, reduces
risk of estrogen receptor-positive breast cancer (odds ratio
= 0.77, $95\%$ CI 0.74-0.81, p = 3.1 × 10-31).},
keywords = {breast cancer risk (Other) / functional annotation (Other)
/ risk locus (Other)},
cin = {C071 / C070 / C020 / C120 / HD01 / C055 / C080 / B072 /
B070},
ddc = {570},
cid = {I:(DE-He78)C071-20160331 / I:(DE-He78)C070-20160331 /
I:(DE-He78)C020-20160331 / I:(DE-He78)C120-20160331 /
I:(DE-He78)HD01-20160331 / I:(DE-He78)C055-20160331 /
I:(DE-He78)C080-20160331 / I:(DE-He78)B072-20160331 /
I:(DE-He78)B070-20160331},
pnm = {313 - Krebsrisikofaktoren und Prävention (POF4-313)},
pid = {G:(DE-HGF)POF4-313},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:34146516},
doi = {10.1016/j.ajhg.2021.05.013},
url = {https://inrepo02.dkfz.de/record/169291},
}