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dc.contributor.authorLakeman, IMM
dc.contributor.authorvan den Broek, AJ
dc.contributor.authorVos, JAM
dc.contributor.authorBarnes, DR
dc.contributor.authorAdlard, J
dc.contributor.authorAndrulis, IL
dc.contributor.authorArason, A
dc.contributor.authorArnold, N
dc.contributor.authorArun, BK
dc.contributor.authorBalmaña, J
dc.contributor.authorBarrowdale, D
dc.contributor.authorBenitez, J
dc.contributor.authorBorg, A
dc.contributor.authorCaldés, T
dc.contributor.authorCaligo, MA
dc.contributor.authorChung, WK
dc.contributor.authorClaes, KBM
dc.contributor.authorGEMO Study Collaborators
dc.contributor.authorEMBRACE Collaborators
dc.contributor.authorCollée, JM
dc.contributor.authorCouch, FJ
dc.contributor.authorDaly, MB
dc.contributor.authorDennis, J
dc.contributor.authorDhawan, M
dc.contributor.authorDomchek, SM
dc.contributor.authorEeles, R
dc.contributor.authorEngel, C
dc.contributor.authorEvans, DG
dc.contributor.authorFeliubadaló, L
dc.contributor.authorForetova, L
dc.contributor.authorFriedman, E
dc.contributor.authorFrost, D
dc.contributor.authorGanz, PA
dc.contributor.authorGarber, J
dc.contributor.authorGayther, SA
dc.contributor.authorGerdes, A-M
dc.contributor.authorGodwin, AK
dc.contributor.authorGoldgar, DE
dc.contributor.authorHahnen, E
dc.contributor.authorHake, CR
dc.contributor.authorHamann, U
dc.contributor.authorHogervorst, FBL
dc.contributor.authorHooning, MJ
dc.contributor.authorHopper, JL
dc.contributor.authorHulick, PJ
dc.contributor.authorImyanitov, EN
dc.contributor.authorOCGN Investigators
dc.contributor.authorHEBON Investigators
dc.contributor.authorKconFab Investigators
dc.contributor.authorIsaacs, C
dc.contributor.authorIzatt, L
dc.contributor.authorJakubowska, A
dc.contributor.authorJames, PA
dc.contributor.authorJanavicius, R
dc.contributor.authorJensen, UB
dc.contributor.authorJiao, Y
dc.contributor.authorJohn, EM
dc.contributor.authorJoseph, V
dc.contributor.authorKarlan, BY
dc.contributor.authorKets, CM
dc.contributor.authorKonstantopoulou, I
dc.contributor.authorKwong, A
dc.contributor.authorLegrand, C
dc.contributor.authorLeslie, G
dc.contributor.authorLesueur, F
dc.contributor.authorLoud, JT
dc.contributor.authorLubiński, J
dc.contributor.authorManoukian, S
dc.contributor.authorMcGuffog, L
dc.contributor.authorMiller, A
dc.contributor.authorGomes, DM
dc.contributor.authorMontagna, M
dc.contributor.authorMouret-Fourme, E
dc.contributor.authorNathanson, KL
dc.contributor.authorNeuhausen, SL
dc.contributor.authorNevanlinna, H
dc.contributor.authorYie, JNY
dc.contributor.authorOlah, E
dc.contributor.authorOlopade, OI
dc.contributor.authorPark, SK
dc.contributor.authorParsons, MT
dc.contributor.authorPeterlongo, P
dc.contributor.authorPiedmonte, M
dc.contributor.authorRadice, P
dc.contributor.authorRantala, J
dc.contributor.authorRennert, G
dc.contributor.authorRisch, HA
dc.contributor.authorSchmutzler, RK
dc.contributor.authorSharma, P
dc.contributor.authorSimard, J
dc.contributor.authorSinger, CF
dc.contributor.authorStadler, Z
dc.contributor.authorStoppa-Lyonnet, D
dc.contributor.authorSutter, C
dc.contributor.authorTan, YY
dc.contributor.authorTeixeira, MR
dc.contributor.authorTeo, SH
dc.contributor.authorTeulé, A
dc.contributor.authorThomassen, M
dc.contributor.authorThull, DL
dc.contributor.authorTischkowitz, M
dc.contributor.authorToland, AE
dc.contributor.authorTung, N
dc.contributor.authorvan Rensburg, EJ
dc.contributor.authorVega, A
dc.contributor.authorWappenschmidt, B
dc.contributor.authorDevilee, P
dc.contributor.authorvan Asperen, CJ
dc.contributor.authorBernstein, JL
dc.contributor.authorOffit, K
dc.contributor.authorEaston, DF
dc.contributor.authorRookus, MA
dc.contributor.authorChenevix-Trench, G
dc.contributor.authorAntoniou, AC
dc.contributor.authorRobson, M
dc.contributor.authorSchmidt, MK
dc.date.accessioned2021-08-12T11:17:04Z
dc.date.available2021-08-12T11:17:04Z
dc.date.issued2021-06-10
dc.identifier.citationGenetics in medicine : official journal of the American College of Medical Genetics, 2021
dc.identifier.issn1098-3600
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/4753
dc.identifier.eissn1530-0366
dc.identifier.eissn1530-0366en_US
dc.identifier.doi10.1038/s41436-021-01198-7
dc.identifier.doi10.1038/s41436-021-01198-7en_US
dc.description.abstractPurpose To evaluate the association between a previously published 313 variant-based breast cancer (BC) polygenic risk score (PRS<sub>313</sub>) and contralateral breast cancer (CBC) risk, in BRCA1 and BRCA2 pathogenic variant heterozygotes.Methods We included women of European ancestry with a prevalent first primary invasive BC (BRCA1 = 6,591 with 1,402 prevalent CBC cases; BRCA2 = 4,208 with 647 prevalent CBC cases) from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), a large international retrospective series. Cox regression analysis was performed to assess the association between overall and ER-specific PRS<sub>313</sub> and CBC risk.Results For BRCA1 heterozygotes the estrogen receptor (ER)-negative PRS<sub>313</sub> showed the largest association with CBC risk, hazard ratio (HR) per SD = 1.12, 95% confidence interval (CI) (1.06-1.18), C-index = 0.53; for BRCA2 heterozygotes, this was the ER-positive PRS<sub>313</sub>, HR = 1.15, 95% CI (1.07-1.25), C-index = 0.57. Adjusting for family history, age at diagnosis, treatment, or pathological characteristics for the first BC did not change association effect sizes. For women developing first BC < age 40 years, the cumulative PRS<sub>313</sub> 5th and 95th percentile 10-year CBC risks were 22% and 32% for BRCA1 and 13% and 23% for BRCA2 heterozygotes, respectively.Conclusion The PRS<sub>313</sub> can be used to refine individual CBC risks for BRCA1/2 heterozygotes of European ancestry, however the PRS<sub>313</sub> needs to be considered in the context of a multifactorial risk model to evaluate whether it might influence clinical decision-making.
dc.formatPrint-Electronic
dc.languageeng
dc.language.isoeng
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectGEMO Study Collaborators
dc.subjectEMBRACE Collaborators
dc.subjectOCGN Investigators
dc.subjectHEBON Investigators
dc.subjectKconFab Investigators
dc.titleThe predictive ability of the 313 variant-based polygenic risk score for contralateral breast cancer risk prediction in women of European ancestry with a heterozygous BRCA1 or BRCA2 pathogenic variant.
dc.typeJournal Article
dcterms.dateAccepted2021-04-26
rioxxterms.versionVoR
rioxxterms.versionofrecord10.1038/s41436-021-01198-7
rioxxterms.licenseref.startdate2021-06-10
rioxxterms.licenseref.startdate2021-06-10en_US
dc.relation.isPartOfGenetics in medicine : official journal of the American College of Medical Genetics
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.embargo.termsNot known
icr.researchteamOncogenetics
icr.researchteamOncogeneticsen_US
dc.contributor.icrauthorEeles, Rosalinden


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