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@ARTICLE{Shimelis:120420,
author = {H. Shimelis and R. L. S. Mesman and C. Von Nicolai and A.
Ehlen and L. Guidugli and C. Martin and F. M. G. R. Calléja
and H. Meeks and E. Hallberg and J. Hinton and J. Lilyquist
and C. Hu and C. M. Aalfs and K. Aittomäki and I. Andrulis
and H. Anton-Culver and V. Arndt$^*$ and M. W. Beckmann and
J. Benitez and N. V. Bogdanova and S. E. Bojesen and M. K.
Bolla and A.-L. Borresen-Dale and H. Brauch$^*$ and P.
Brennan and H. Brenner$^*$ and A. Broeks and B. Brouwers and
T. Brüning and B. Burwinkel$^*$ and J. Chang-Claude$^*$ and
G. Chenevix-Trench and C.-Y. Cheng and J.-Y. Choi and J. M.
Collée and A. Cox and S. S. Cross and K. Czene and H.
Darabi and J. Dennis and T. Dörk and I. Dos-Santos-Silva
and A. M. Dunning and P. A. Fasching and J. Figueroa and H.
Flyger and M. García-Closas and G. G. Giles and G. Glendon
and P. Guénel and C. A. Haiman and P. Hall and U.
Hamann$^*$ and M. Hartman and F. B. Hogervorst and A.
Hollestelle and J. L. Hopper and H. Ito and A. Jakubowska
and D. Kang and V.-M. Kosma and V. Kristensen and K.-N. Lai
and D. Lambrechts and L. L. Marchand and J. Li and A.
Lindblom and A. Lophatananon and J. Lubinski and E.
Machackova and A. Mannermaa and S. Margolin and F. Marme and
K. Matsuo and H. Miao and K. Michailidou and R. L. Milne and
K. Muir and S. L. Neuhausen and H. Nevanlinna and J. E.
Olson and C. Olswold and J. J. C. Oosterwijk and A. Osorio
and P. Peterlongo and J. Peto and P. D. P. Pharoah and K.
Pylkäs and P. Radice and M. U. Rashid and V. Rhenius and A.
Rudolph$^*$ and S. Sangrajrang and E. J. Sawyer and M. K.
Schmidt and M. J. Schoemaker and C. Seynaeve and M. Shah and
C.-Y. Shen and M. Shrubsole and X.-O. Shu and S. Slager and
M. C. Southey and D. O. Stram and A. Swerdlow and S. H. Teo
and I. Tomlinson and D. Torres and T. Truong and C. J. van
Asperen and L. E. van der Kolk and Q. Wang and R. Winqvist
and A. H. Wu and J.-C. Yu and W. Zheng and Y. Zheng and J.
Leary and L. Walker and L. Foretova and F. Fostira and K. B.
M. Claes and L. Varesco and S. Moghadasi and D. F. Easton
and A. Spurdle and P. Devilee and H. Vrieling and A. N. A.
Monteiro and D. E. Goldgar and A. Carreira and M. P. G.
Vreeswijk and F. J. Couch},
collaboration = {f. k. Investigators and for {NBCS Collaborators}},
title = {{BRCA}2 {H}ypomorphic {M}issense {V}ariants {C}onfer
{M}oderate {R}isks of {B}reast {C}ancer.},
journal = {Cancer research},
volume = {77},
number = {11},
issn = {1538-7445},
address = {Philadelphia, Pa.},
publisher = {AACR},
reportid = {DKFZ-2017-00849},
pages = {2789-2799},
year = {2017},
abstract = {Breast cancer risks conferred by many germline missense
variants in the BRCA1 and BRCA2 genes, often referred to as
variants of uncertain significance (VUS), have not been
established. In this study, associations between 19 BRCA1
and 33 BRCA2 missense substitution variants and breast
cancer risk were investigated through a breast cancer
case-control study using genotyping data from 38 studies of
predominantly European ancestry (41,890 cases and 41,607
controls) and nine studies of Asian ancestry (6,269 cases
and 6,624 controls). The BRCA2 c.9104A>C, p.Tyr3035Ser (OR =
2.52; P = 0.04), and BRCA1 c.5096G>A, p.Arg1699Gln (OR =
4.29; P = 0.009) variant were associated with moderately
increased risks of breast cancer among Europeans, whereas
BRCA2 c.7522G>A, p.Gly2508Ser (OR = 2.68; P = 0.004), and
c.8187G>T, p.Lys2729Asn (OR = 1.4; P = 0.004) were
associated with moderate and low risks of breast cancer
among Asians. Functional characterization of the BRCA2
variants using four quantitative assays showed reduced BRCA2
activity for p.Tyr3035Ser compared with wild-type. Overall,
our results show how BRCA2 missense variants that influence
protein function can confer clinically relevant, moderately
increased risks of breast cancer, with potential
implications for risk management guidelines in women with
these specific variants. Cancer Res; 77(11); 1-11. ©2017
AACR.},
cin = {C071 / C070 / G110 / C080 / C020 / B072 / L801 / L101},
ddc = {610},
cid = {I:(DE-He78)C071-20160331 / I:(DE-He78)C070-20160331 /
I:(DE-He78)G110-20160331 / I:(DE-He78)C080-20160331 /
I:(DE-He78)C020-20160331 / I:(DE-He78)B072-20160331 /
I:(DE-He78)L801-20160331 / I:(DE-He78)L101-20160331},
pnm = {313 - Cancer risk factors and prevention (POF3-313)},
pid = {G:(DE-HGF)POF3-313},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:28283652},
doi = {10.1158/0008-5472.CAN-16-2568},
url = {https://inrepo02.dkfz.de/record/120420},
}