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dc.contributor.authorBarnes, Daniel R.
dc.contributor.authorRookus, Matti A.
dc.contributor.authorMcGuffog, Lesley
dc.contributor.authorLeslie, Goska
dc.contributor.authorMooij, Thea M.
dc.contributor.authorDennis, Joe
dc.contributor.authorMavaddat, Nasim
dc.contributor.authorAdlard, Julian
dc.contributor.authorAhmed, Munaza
dc.contributor.authorAittomäki, Kristiina
dc.contributor.authorAndrieu, Nadine
dc.contributor.authorAndrulis, Irene L.
dc.contributor.authorArnold, Norbert
dc.contributor.authorArun, Banu K.
dc.contributor.authorAzzollini, Jacopo
dc.contributor.authorBalmaña, Judith
dc.contributor.authorBarkardottir, Rosa B.
dc.contributor.authorBarrowdale, Daniel
dc.contributor.authorBenitez, Javier
dc.contributor.authorBerthet, Pascaline
dc.contributor.authorBiałkowska, Katarzyna
dc.contributor.authorBlanco, Amie M.
dc.contributor.authorBlok, Marinus J.
dc.contributor.authorBonanni, Bernardo
dc.contributor.authorBoonen, Susanne E.
dc.contributor.authorBorg, Åke
dc.contributor.authorBozsik, Aniko
dc.contributor.authorBradbury, Angela R.
dc.contributor.authorBrennan, Paul
dc.contributor.authorBrewer, Carole
dc.contributor.authorBrunet, Joan
dc.contributor.authorBuys, Saundra S.
dc.contributor.authorCaldés, Trinidad
dc.contributor.authorCaligo, Maria A.
dc.contributor.authorCampbell, Ian
dc.contributor.authorChristensen, Lise Lotte
dc.contributor.authorChung, Wendy K.
dc.contributor.authorClaes, Kathleen B. M.
dc.contributor.authorColas, Chrystelle
dc.contributor.authorCollonge-Rame, Marie-Agnès
dc.contributor.authorCook, Jackie
dc.contributor.authorDaly, Mary B.
dc.contributor.authorDavidson, Rosemarie
dc.contributor.authorde la Hoya, Miguel
dc.contributor.authorde Putter, Robin
dc.contributor.authorDelnatte, Capucine
dc.contributor.authorDevilee, Peter
dc.contributor.authorDiez, Orland
dc.contributor.authorDing, Yuan Chun
dc.contributor.authorDomchek, Susan M.
dc.contributor.authorDorfling, Cecilia M.
dc.contributor.authorDumont, Martine
dc.contributor.authorEeles, Ros
dc.contributor.authorEjlertsen, Bent
dc.contributor.authorEngel, Christoph
dc.contributor.authorEvans, D. Gareth
dc.contributor.authorFaivre, Laurence
dc.contributor.authorForetova, Lenka
dc.contributor.authorFostira, Florentia
dc.contributor.authorFriedlander, Michael
dc.contributor.authorFriedman, Eitan
dc.contributor.authorFrost, Debra
dc.contributor.authorGanz, Patricia A.
dc.contributor.authorGarber, Judy
dc.contributor.authorGehrig, Andrea
dc.contributor.authorGerdes, Anne-Marie
dc.contributor.authorGesta, Paul
dc.contributor.authorGiraud, Sophie
dc.contributor.authorGlendon, Gord
dc.contributor.authorGodwin, Andrew K.
dc.contributor.authorGoldgar, David E.
dc.contributor.authorGonzález-Neira, Anna
dc.contributor.authorGreene, Mark H.
dc.contributor.authorGschwantler-Kaulich, Daphne
dc.contributor.authorHahnen, Eric
dc.contributor.authorHamann, Ute
dc.contributor.authorHanson, Helen
dc.contributor.authorHentschel, Julia
dc.contributor.authorHogervorst, Frans B. L.
dc.contributor.authorHooning, Maartje J.
dc.contributor.authorHorvath, Judit
dc.contributor.authorHu, Chunling
dc.contributor.authorHulick, Peter J.
dc.contributor.authorImyanitov, Evgeny N.
dc.contributor.authorIsaacs, Claudine
dc.contributor.authorIzatt, Louise
dc.contributor.authorIzquierdo, Angel
dc.contributor.authorJakubowska, Anna
dc.contributor.authorJames, Paul A.
dc.contributor.authorJanavicius, Ramunas
dc.contributor.authorJohn, Esther M.
dc.contributor.authorJoseph, Vijai
dc.contributor.authorKarlan, Beth Y.
dc.contributor.authorKast, Karin
dc.contributor.authorKoudijs, Marco
dc.contributor.authorKruse, Torben A.
dc.contributor.authorKwong, Ava
dc.contributor.authorLaitman, Yael
dc.contributor.authorLasset, Christine
dc.contributor.authorLazaro, Conxi
dc.contributor.authorLester, Jenny
dc.contributor.authorLesueur, Fabienne
dc.contributor.authorLiljegren, Annelie
dc.contributor.authorLoud, Jennifer T.
dc.contributor.authorLubiński, Jan
dc.contributor.authorMai, Phuong L.
dc.contributor.authorManoukian, Siranoush
dc.contributor.authorMari, Véronique
dc.contributor.authorMebirouk, Noura
dc.contributor.authorMeijers-Heijboer, Hanne E. J.
dc.contributor.authorMeindl, Alfons
dc.contributor.authorMensenkamp, Arjen R.
dc.contributor.authorMiller, Austin
dc.contributor.authorMontagna, Marco
dc.contributor.authorMouret-Fourme, Emmanuelle
dc.contributor.authorMukherjee, Semanti
dc.contributor.authorMulligan, Anna Marie
dc.contributor.authorNathanson, Katherine L.
dc.contributor.authorNeuhausen, Susan L.
dc.contributor.authorNevanlinna, Heli
dc.contributor.authorNiederacher, Dieter
dc.contributor.authorNielsen, Finn Cilius
dc.contributor.authorNikitina-Zake, Liene
dc.contributor.authorNoguès, Catherine
dc.contributor.authorOlah, Edith
dc.contributor.authorOlopade, Olufunmilayo I.
dc.contributor.authorOng, Kai-ren
dc.contributor.authorO’Shaughnessy-Kirwan, Aoife
dc.contributor.authorOsorio, Ana
dc.contributor.authorOtt, Claus-Eric
dc.contributor.authorPapi, Laura
dc.contributor.authorPark, Sue K.
dc.contributor.authorParsons, Michael T.
dc.contributor.authorPedersen, Inge Sokilde
dc.contributor.authorPeissel, Bernard
dc.contributor.authorPeixoto, Ana
dc.contributor.authorPeterlongo, Paolo
dc.contributor.authorPfeiler, Georg
dc.contributor.authorPhillips, Kelly-Anne
dc.contributor.authorPrajzendanc, Karolina
dc.contributor.authorPujana, Miquel Angel
dc.contributor.authorRadice, Paolo
dc.contributor.authorRamser, Juliane
dc.contributor.authorRamus, Susan J.
dc.contributor.authorRantala, Johanna
dc.contributor.authorRennert, Gad
dc.contributor.authorRisch, Harvey A.
dc.contributor.authorRobson, Mark
dc.contributor.authorRønlund, Karina
dc.contributor.authorSalani, Ritu
dc.contributor.authorSchuster, Hélène
dc.contributor.authorSenter, Leigha
dc.contributor.authorShah, Payal D.
dc.contributor.authorSharma, Priyanka
dc.contributor.authorSide, Lucy E.
dc.contributor.authorSinger, Christian F.
dc.contributor.authorSlavin, Thomas P.
dc.contributor.authorSoucy, Penny
dc.contributor.authorSouthey, Melissa C.
dc.contributor.authorSpurdle, Amanda B.
dc.contributor.authorSteinemann, Doris
dc.contributor.authorSteinsnyder, Zoe
dc.contributor.authorStoppa-Lyonnet, Dominique
dc.contributor.authorSutter, Christian
dc.contributor.authorTan, Yen Yen
dc.contributor.authorTeixeira, Manuel R.
dc.contributor.authorTeo, Soo Hwang
dc.contributor.authorThull, Darcy L.
dc.contributor.authorTischkowitz, Marc
dc.contributor.authorTognazzo, Silvia
dc.contributor.authorToland, Amanda E.
dc.contributor.authorTrainer, Alison H.
dc.contributor.authorTung, Nadine
dc.contributor.authorvan Engelen, Klaartje
dc.contributor.authorvan Rensburg, Elizabeth J.
dc.contributor.authorVega, Ana
dc.contributor.authorVierstraete, Jeroen
dc.contributor.authorWagner, Gabriel
dc.contributor.authorWalker, Lisa
dc.contributor.authorWang-Gohrke, Shan
dc.contributor.authorWappenschmidt, Barbara
dc.contributor.authorWeitzel, Jeffrey N.
dc.contributor.authorYadav, Siddhartha
dc.contributor.authorYang, Xin
dc.contributor.authorYannoukakos, Drakoulis
dc.contributor.authorZimbalatti, Dario
dc.contributor.authorOffit, Kenneth
dc.contributor.authorThomassen, Mads
dc.contributor.authorCouch, Fergus J.
dc.contributor.authorSchmutzler, Rita K.
dc.contributor.authorSimard, Jacques
dc.contributor.authorEaston, Douglas F.
dc.contributor.authorChenevix-Trench, Georgia
dc.contributor.authorAntoniou, Antonis C.
dc.contributor.authorAntoniou, Antonis
dc.contributor.authorEaston, Douglas
dc.contributor.authorSide, Lucy
dc.contributor.authorSpurdle, Amanda
dc.contributor.authorBlok, Marinus
dc.contributor.authorHogervorst, Frans
dc.contributor.authorHooning, Maartje
dc.contributor.authorMensenkamp, Arjen
dc.contributor.authorMeijers-Heijboer, Hanne
dc.contributor.authorRookus, Matti
dc.contributor.authorEngelen, Klaartje van
dc.date.accessioned2021-02-12T17:31:04Z
dc.date.available2021-02-12T17:31:04Z
dc.date.issued2020-07-15
dc.date.submitted2019-11-27
dc.identifier.issn1098-3600
dc.identifier.others41436-020-0862-x
dc.identifier.other862
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/317571
dc.description.abstractAbstract: Purpose: We assessed the associations between population-based polygenic risk scores (PRS) for breast (BC) or epithelial ovarian cancer (EOC) with cancer risks for BRCA1 and BRCA2 pathogenic variant carriers. Methods: Retrospective cohort data on 18,935 BRCA1 and 12,339 BRCA2 female pathogenic variant carriers of European ancestry were available. Three versions of a 313 single-nucleotide polymorphism (SNP) BC PRS were evaluated based on whether they predict overall, estrogen receptor (ER)–negative, or ER-positive BC, and two PRS for overall or high-grade serous EOC. Associations were validated in a prospective cohort. Results: The ER-negative PRS showed the strongest association with BC risk for BRCA1 carriers (hazard ratio [HR] per standard deviation = 1.29 [95% CI 1.25–1.33], P = 3×10−72). For BRCA2, the strongest association was with overall BC PRS (HR = 1.31 [95% CI 1.27–1.36], P = 7×10−50). HR estimates decreased significantly with age and there was evidence for differences in associations by predicted variant effects on protein expression. The HR estimates were smaller than general population estimates. The high-grade serous PRS yielded the strongest associations with EOC risk for BRCA1 (HR = 1.32 [95% CI 1.25–1.40], P = 3×10−22) and BRCA2 (HR = 1.44 [95% CI 1.30–1.60], P = 4×10−12) carriers. The associations in the prospective cohort were similar. Conclusion: Population-based PRS are strongly associated with BC and EOC risks for BRCA1/2 carriers and predict substantial absolute risk differences for women at PRS distribution extremes.
dc.languageen
dc.publisherNature Publishing Group US
dc.rightsAttribution 4.0 International (CC BY 4.0)en
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en
dc.subjectArticle
dc.subjectarticle
dc.subjectBRCA1/2
dc.subjectbreast cancer
dc.subjectovarian cancer
dc.subjectPRS
dc.subjectgenetics
dc.titlePolygenic risk scores and breast and epithelial ovarian cancer risks for carriers of BRCA1 and BRCA2 pathogenic variants
dc.typeArticle
dc.date.updated2021-02-12T17:31:04Z
prism.endingPage1666
prism.issueIdentifier10
prism.publicationNameGenetics in Medicine
prism.startingPage1653
prism.volume22
dc.identifier.doi10.17863/CAM.64684
dcterms.dateAccepted2020-05-29
rioxxterms.versionofrecord10.1038/s41436-020-0862-x
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/
dc.identifier.eissn1530-0366


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Attribution 4.0 International (CC BY 4.0)
Except where otherwise noted, this item's licence is described as Attribution 4.0 International (CC BY 4.0)