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P., Antoniou, Antonis C., Chatterjee, Nilanjan, Kraft, Peter ORCID: 0000-0002-4472-8103, Garcia-Closas, Montserrat and Easton, Douglas F. (2019). Polygenic Risk Scores for Prediction of Breast Cancer and Breast Cancer Subtypes. Am. J. Hum. Genet., 104 (1). S. 21 - 35. CAMBRIDGE: CELL PRESS. ISSN 1537-6605

Full text not available from this repository.

Abstract

Stratification of women according to their risk of breast cancer based on polygenic risk scores (PRSs) could improve screening and prevention strategies. Our aim was to develop PRSs, optimized for prediction of estrogen receptor (ER)-specific disease, from the largest available genome-wide association dataset and to empirically validate the PRSs in prospective studies. The development dataset comprised 94,075 case subjects and 75,017 control subjects of European ancestry from 69 studies, divided into training and validation sets. Samples were genotyped using genome-wide arrays, and single-nucleotide polymorphisms (SNPs) were selected by stepwise regression or lasso penalized regression. The best performing PRSs were validated in an independent test set comprising 11,428 case subjects and 18,323 control subjects from 10 prospective studies and 190,040 women from UK Biobank (3,215 incident breast cancers). For the best PRSs (313 SNPs), the odds ratio for overall disease per 1 standard deviation in ten prospective studies was 1.61 (95%CI: 1.57-1.65) with area under receiver-operator curve (AUC) = 0.630 (95%CI: 0.628-0.651). The lifetime risk of overall breast cancer in the top centile of the PRSs was 32.6%. Compared with women in the middle quintile, those in the highest 1% of risk had 4.37- and 2.78-fold risks, and those in the lowest 1% of risk had 0.16- and 0.27-fold risks, of developing ER-positive and ER-negative disease, respectively. Goodness-of-fit tests indicated that this PRS was well calibrated and predicts disease risk accurately in the tails of the distribution. This PRS is a powerful and reliable predictor of breast cancer risk that may improve breast cancer prevention programs.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Mavaddat, NasimUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Michailidou, KyriakiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dennis, JoeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lush, MichaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fachal, LauraUNSPECIFIEDorcid.org/0000-0002-7256-9752UNSPECIFIED
Lee, AndrewUNSPECIFIEDorcid.org/0000-0003-0677-0252UNSPECIFIED
Tyrer, Jonathan P.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Chen, Ting-HueiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wang, QinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bolla, Manjeet K.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Yang, XinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Adank, Muriel A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ahearn, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Aittomaki, KristiinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Allen, JamieUNSPECIFIEDorcid.org/0000-0002-8677-2225UNSPECIFIED
Andrulis, Irene L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Anton-Culver, HodaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Antonenkova, Natalia N.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Arndt, VolkerUNSPECIFIEDorcid.org/0000-0001-9320-8684UNSPECIFIED
Aronson, Kristan J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Auer, Paul L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Auvinen, PaiviUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Barrdahl, MyrtoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Freeman, Laura E. BeaneUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Beckmann, Matthias W.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Behrens, SabineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Benitez, JavierUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bermisheva, MarinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bernstein, LeslieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Blomqvist, CarlUNSPECIFIEDorcid.org/0000-0003-3041-1938UNSPECIFIED
Bogdanova, Natalia, VUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bojesen, Stig E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bonanni, BernardoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Borresen-Dale, Anne-LiseUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Brauch, HiltrudUNSPECIFIEDorcid.org/0000-0001-7531-2736UNSPECIFIED
Bremer, MichaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Brenner, HermannUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Brentnall, AdamUNSPECIFIEDorcid.org/0000-0001-6327-4357UNSPECIFIED
Brock, Ian W.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Brooks-Wilson, AngelaUNSPECIFIEDorcid.org/0000-0003-1009-6408UNSPECIFIED
Brucker, Sara Y.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bruening, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Burwinkel, BarbaraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Campa, DanieleUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Carter, Brian D.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Castelao, Jose E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Chanock, Stephen J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Chlebowski, RowanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Christiansen, HansUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Clarke, Christine L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Collee, J. MargrietUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cordina-Duverger, EmilieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cornelissen, StenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Couch, Fergus J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cox, AngelaUNSPECIFIEDorcid.org/0000-0002-5138-1099UNSPECIFIED
Cross, Simon S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Czene, KamilaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Daly, Mary B.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Devilee, PeterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Doerk, ThiloUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
dos-Santos-Silva, IsabelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dumont, MartineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Durcan, LorraineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dwek, MiriamUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Eccles, Diana M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ekici, Arif B.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Eliassen, A. HeatherUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ellberg, CarolinaUNSPECIFIEDorcid.org/0000-0001-7297-0645UNSPECIFIED
Engel, ChristophUNSPECIFIEDorcid.org/0000-0002-7247-282XUNSPECIFIED
Eriksson, MikaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Evans, D. GarethUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fasching, Peter A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Figueroa, JonineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fletcher, OliviaUNSPECIFIEDorcid.org/0000-0001-9387-7116UNSPECIFIED
Flyger, HenrikUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
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Fritschi, LinUNSPECIFIEDorcid.org/0000-0002-7692-3560UNSPECIFIED
Gabrielson, MarikeUNSPECIFIEDorcid.org/0000-0002-3171-1556UNSPECIFIED
Gago-Dominguez, ManuelaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gapstur, Susan M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Garcia-Saenz, Jose A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gaudet, Mia M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Georgoulias, VassiliosUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Giles, Graham G.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gilyazova, Irina R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
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Goldgar, David E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gonzalez-Neira, AnnaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Alnaes, Grethe I. GrenakerUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Grip, MerviUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
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Scott, Rodney J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
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Shrubsole, Martha J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Shu, Xiao-OuUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Slager, SusanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Smeets, AnnUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
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Soucy, PennyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Southey, Melissa C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Spinelli, John J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Stegmaier, ChristaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
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Walker, LoganUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
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Spurdle, MandyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
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Gleeson, MargaretUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
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Lakhani, SunilUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dudding, TracyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
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Ottestad, LarsUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Karesen, RolfUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schlichting, EllenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Holmen, Marit MuriUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
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Haakensen, VildeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Engebraten, OlavUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Naume, BjornUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fossa, AlexanderUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kiserud, Cecile E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Reinertsen, Kristin, VUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Helland, AslaugUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Riis, MargitUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Geisler, JuergenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dunning, Alison M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Thompson, Deborah J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Chenevix-Trench, GeorgiaUNSPECIFIEDorcid.org/0000-0002-1878-2587UNSPECIFIED
Chang-Claude, JennyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schmidt, Marjanka K.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hall, PerUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Milne, Roger L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pharoah, Paul D. P.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Antoniou, Antonis C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Chatterjee, NilanjanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kraft, PeterUNSPECIFIEDorcid.org/0000-0002-4472-8103UNSPECIFIED
Garcia-Closas, MontserratUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Easton, Douglas F.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-159517
DOI: 10.1016/j.ajhg.2018.11.002
Journal or Publication Title: Am. J. Hum. Genet.
Volume: 104
Number: 1
Page Range: S. 21 - 35
Date: 2019
Publisher: CELL PRESS
Place of Publication: CAMBRIDGE
ISSN: 1537-6605
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
GENOME-WIDE ASSOCIATION; FUNCTIONAL VARIANTS; PROSTATE-CANCER; SUSCEPTIBILITY; SHRINKAGE; MODELS; LOCUS; WOMENMultiple languages
Genetics & HeredityMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/15951

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