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dc.contributor.authorBarnes, DR
dc.contributor.authorRookus, MA
dc.contributor.authorMcGuffog, L
dc.contributor.authorLeslie, G
dc.contributor.authorMooij, TM
dc.contributor.authorDennis, J
dc.contributor.authorMavaddat, N
dc.contributor.authorAdlard, J
dc.contributor.authorAhmed, M
dc.contributor.authorAittomäki, K
dc.contributor.authorAndrieu, N
dc.contributor.authorAndrulis, IL
dc.contributor.authorArnold, N
dc.contributor.authorArun, BK
dc.contributor.authorAzzollini, J
dc.contributor.authorBalmaña, J
dc.contributor.authorBarkardottir, RB
dc.contributor.authorBarrowdale, D
dc.contributor.authorBenitez, J
dc.contributor.authorBerthet, P
dc.contributor.authorBiałkowska, K
dc.contributor.authorBlanco, AM
dc.contributor.authorBlok, MJ
dc.contributor.authorBonanni, B
dc.contributor.authorBoonen, SE
dc.contributor.authorBorg, Å
dc.contributor.authorBozsik, A
dc.contributor.authorBradbury, AR
dc.contributor.authorBrennan, P
dc.contributor.authorBrewer, C
dc.contributor.authorBrunet, J
dc.contributor.authorBuys, SS
dc.contributor.authorCaldés, T
dc.contributor.authorCaligo, MA
dc.contributor.authorCampbell, I
dc.contributor.authorChristensen, LL
dc.contributor.authorChung, WK
dc.contributor.authorClaes, KBM
dc.contributor.authorColas, C
dc.contributor.authorGEMO Study Collaborators,
dc.contributor.authorEMBRACE Collaborators,
dc.contributor.authorCollonge-Rame, M-A
dc.contributor.authorCook, J
dc.contributor.authorDaly, MB
dc.contributor.authorDavidson, R
dc.contributor.authorde la Hoya, M
dc.contributor.authorde Putter, R
dc.contributor.authorDelnatte, C
dc.contributor.authorDevilee, P
dc.contributor.authorDiez, O
dc.contributor.authorDing, YC
dc.contributor.authorDomchek, SM
dc.contributor.authorDorfling, CM
dc.contributor.authorDumont, M
dc.contributor.authorEeles, R
dc.contributor.authorEjlertsen, B
dc.contributor.authorEngel, C
dc.contributor.authorEvans, DG
dc.contributor.authorFaivre, L
dc.contributor.authorForetova, L
dc.contributor.authorFostira, F
dc.contributor.authorFriedlander, M
dc.contributor.authorFriedman, E
dc.contributor.authorFrost, D
dc.contributor.authorGanz, PA
dc.contributor.authorGarber, J
dc.contributor.authorGehrig, A
dc.contributor.authorGerdes, A-M
dc.contributor.authorGesta, P
dc.contributor.authorGiraud, S
dc.contributor.authorGlendon, G
dc.contributor.authorGodwin, AK
dc.contributor.authorGoldgar, DE
dc.contributor.authorGonzález-Neira, A
dc.contributor.authorGreene, MH
dc.contributor.authorGschwantler-Kaulich, D
dc.contributor.authorHahnen, E
dc.contributor.authorHamann, U
dc.contributor.authorHanson, H
dc.contributor.authorHentschel, J
dc.contributor.authorHogervorst, FBL
dc.contributor.authorHooning, MJ
dc.contributor.authorHorvath, J
dc.contributor.authorHu, C
dc.contributor.authorHulick, PJ
dc.contributor.authorImyanitov, EN
dc.contributor.authorkConFab Investigators,
dc.contributor.authorHEBON Investigators,
dc.contributor.authorGENEPSO Investigators,
dc.contributor.authorIsaacs, C
dc.contributor.authorIzatt, L
dc.contributor.authorIzquierdo, A
dc.contributor.authorJakubowska, A
dc.contributor.authorJames, PA
dc.contributor.authorJanavicius, R
dc.contributor.authorJohn, EM
dc.contributor.authorJoseph, V
dc.contributor.authorKarlan, BY
dc.contributor.authorKast, K
dc.contributor.authorKoudijs, M
dc.contributor.authorKruse, TA
dc.contributor.authorKwong, A
dc.contributor.authorLaitman, Y
dc.contributor.authorLasset, C
dc.contributor.authorLazaro, C
dc.contributor.authorLester, J
dc.contributor.authorLesueur, F
dc.contributor.authorLiljegren, A
dc.contributor.authorLoud, JT
dc.contributor.authorLubiński, J
dc.contributor.authorMai, PL
dc.contributor.authorManoukian, S
dc.contributor.authorMari, V
dc.contributor.authorMebirouk, N
dc.contributor.authorMeijers-Heijboer, HEJ
dc.contributor.authorMeindl, A
dc.contributor.authorMensenkamp, AR
dc.contributor.authorMiller, A
dc.contributor.authorMontagna, M
dc.contributor.authorMouret-Fourme, E
dc.contributor.authorMukherjee, S
dc.contributor.authorMulligan, AM
dc.contributor.authorNathanson, KL
dc.contributor.authorNeuhausen, SL
dc.contributor.authorNevanlinna, H
dc.contributor.authorNiederacher, D
dc.contributor.authorNielsen, FC
dc.contributor.authorNikitina-Zake, L
dc.contributor.authorNoguès, C
dc.contributor.authorOlah, E
dc.contributor.authorOlopade, OI
dc.contributor.authorOng, K-R
dc.contributor.authorO'Shaughnessy-Kirwan, A
dc.contributor.authorOsorio, A
dc.contributor.authorOtt, C-E
dc.contributor.authorPapi, L
dc.contributor.authorPark, SK
dc.contributor.authorParsons, MT
dc.contributor.authorPedersen, IS
dc.contributor.authorPeissel, B
dc.contributor.authorPeixoto, A
dc.contributor.authorPeterlongo, P
dc.contributor.authorPfeiler, G
dc.contributor.authorPhillips, K-A
dc.contributor.authorPrajzendanc, K
dc.contributor.authorPujana, MA
dc.contributor.authorRadice, P
dc.contributor.authorRamser, J
dc.contributor.authorRamus, SJ
dc.contributor.authorRantala, J
dc.contributor.authorRennert, G
dc.contributor.authorRisch, HA
dc.contributor.authorRobson, M
dc.contributor.authorRønlund, K
dc.contributor.authorSalani, R
dc.contributor.authorSchuster, H
dc.contributor.authorSenter, L
dc.contributor.authorShah, PD
dc.contributor.authorSharma, P
dc.contributor.authorSide, LE
dc.contributor.authorSinger, CF
dc.contributor.authorSlavin, TP
dc.contributor.authorSoucy, P
dc.contributor.authorSouthey, MC
dc.contributor.authorSpurdle, AB
dc.contributor.authorSteinemann, D
dc.contributor.authorSteinsnyder, Z
dc.contributor.authorStoppa-Lyonnet, D
dc.contributor.authorSutter, C
dc.contributor.authorTan, YY
dc.contributor.authorTeixeira, MR
dc.contributor.authorTeo, SH
dc.contributor.authorThull, DL
dc.contributor.authorTischkowitz, M
dc.contributor.authorTognazzo, S
dc.contributor.authorToland, AE
dc.contributor.authorTrainer, AH
dc.contributor.authorTung, N
dc.contributor.authorvan Engelen, K
dc.contributor.authorvan Rensburg, EJ
dc.contributor.authorVega, A
dc.contributor.authorVierstraete, J
dc.contributor.authorWagner, G
dc.contributor.authorWalker, L
dc.contributor.authorWang-Gohrke, S
dc.contributor.authorWappenschmidt, B
dc.contributor.authorWeitzel, JN
dc.contributor.authorYadav, S
dc.contributor.authorYang, X
dc.contributor.authorYannoukakos, D
dc.contributor.authorZimbalatti, D
dc.contributor.authorOffit, K
dc.contributor.authorThomassen, M
dc.contributor.authorCouch, FJ
dc.contributor.authorSchmutzler, RK
dc.contributor.authorSimard, J
dc.contributor.authorEaston, DF
dc.contributor.authorChenevix-Trench, G
dc.contributor.authorAntoniou, AC
dc.contributor.authorConsortium of Investigators of Modifiers of BRCA and BRCA2,
dc.date.accessioned2020-08-12T11:08:07Z
dc.date.issued2020-10-01
dc.identifier.citationGenetics in medicine : official journal of the American College of Medical Genetics, 2020, 22 (10), pp. 1653 - 1666
dc.identifier.issn1098-3600
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/3930
dc.identifier.eissn1530-0366
dc.identifier.doi10.1038/s41436-020-0862-x
dc.description.abstractPURPOSE: 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.formatPrint-Electronic
dc.format.extent1653 - 1666
dc.languageeng
dc.language.isoeng
dc.publisherELSEVIER SCIENCE INC
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.subjectGEMO Study Collaborators
dc.subjectEMBRACE Collaborators
dc.subjectkConFab Investigators
dc.subjectHEBON Investigators
dc.subjectGENEPSO Investigators
dc.subjectConsortium of Investigators of Modifiers of BRCA and BRCA2
dc.titlePolygenic risk scores and breast and epithelial ovarian cancer risks for carriers of BRCA1 and BRCA2 pathogenic variants.
dc.typeJournal Article
dcterms.dateAccepted2020-05-29
rioxxterms.versionofrecord10.1038/s41436-020-0862-x
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
rioxxterms.licenseref.startdate2020-10
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfGenetics in medicine : official journal of the American College of Medical Genetics
pubs.issue10
pubs.notesNot known
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Genetics and Epidemiology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Genetics and Epidemiology/Oncogenetics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Oncogenetics
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Genetics and Epidemiology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Genetics and Epidemiology/Oncogenetics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Oncogenetics
pubs.publication-statusPublished
pubs.volume22
pubs.embargo.termsNot known
icr.researchteamOncogenetics
dc.contributor.icrauthorEeles, Rosalind


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