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dc.contributor.authorMavaddat, N
dc.contributor.authorMichailidou, K
dc.contributor.authorDennis, J
dc.contributor.authorLush, M
dc.contributor.authorFachal, L
dc.contributor.authorLee, A
dc.contributor.authorTyrer, JP
dc.contributor.authorChen, TH
dc.contributor.authorWang, Q
dc.contributor.authorBolla, MK
dc.contributor.authorYang, X
dc.contributor.authorAdank, MA
dc.contributor.authorAhearn, T
dc.contributor.authorAittomäki, K
dc.contributor.authorAllen, J
dc.contributor.authorAndrulis, IL
dc.contributor.authorAnton-Culver, H
dc.contributor.authorAntonenkova, NN
dc.contributor.authorArndt, V
dc.contributor.authorAronson KJ
dc.contributor.authoret al. [Incl Auvinen, Päivi; Kataja, Vesa; Kosma, Veli-Matti; Mannermaa, Arto]
dc.date.accessioned2019-01-17T09:46:09Z
dc.date.available2019-01-17T09:46:09Z
dc.date.issued2019
dc.identifier.urihttps://erepo.uef.fi/handle/123456789/7342
dc.description.abstractStratification 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.
dc.language.isoenglanti
dc.publisherElsevier BV
dc.relation.ispartofseriesAMERICAN JOURNAL OF HUMAN GENETICS
dc.relation.urihttp://dx.doi.org/10.1016/j.ajhg.2018.11.002
dc.rightsCC BY-NC-ND https://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subjectbreast
dc.subjectcancer
dc.subjectrisk
dc.subjectpolygenic
dc.subjectstratification
dc.subjectgenetic
dc.subjectepidemiology
dc.subjectscreening
dc.subjectprediction
dc.subjectscore
dc.titlePolygenic Risk Scores for Prediction of Breast Cancer and Breast Cancer Subtypes
dc.description.versionpublished version
dc.contributor.departmentSchool of Medicine / Clinical Medicine
uef.solecris.id59194248en
dc.type.publicationTieteelliset aikakauslehtiartikkelit
dc.rights.accessrights© Authors
dc.relation.projectidinfo:eu-repo/grantAgreement/EC/FP7-HEALTH/223175/EU/Collaborative Oncological Gene-environment Study/COGS
dc.relation.projectidinfo:eu-repo/grantAgreement/EC/H2020-EU.3.1.1./633784/EU/Breast CAncer STratification: understanding the determinants of risk and prognosis of molecular subtypes/B-CAST
dc.relation.projectidinfo:eu-repo/grantAgreement/EC/H2020-EU.3.1.2./634935/EU/Breast Cancer Risk after Diagnostic Gene Sequencing/BRIDGES
dc.relation.doi10.1016/j.ajhg.2018.11.002
dc.description.reviewstatuspeerReviewed
dc.format.pagerange21-34
dc.relation.issn0002-9297
dc.relation.issue1
dc.relation.volume104
dc.rights.accesslevelopenAccess
dc.type.okmA1
uef.solecris.openaccessHybridijulkaisukanavassa ilmestynyt avoin julkaisu


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