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dc.contributor.authorYang, X
dc.contributor.authorSong, H
dc.contributor.authorLeslie, G
dc.contributor.authorEngel, C
dc.contributor.authorHahnen, E
dc.contributor.authorAuber, B
dc.contributor.authorHorváth, J
dc.contributor.authorKast, K
dc.contributor.authorNiederacher, D
dc.contributor.authorTurnbull, C
dc.contributor.authorHoulston, R
dc.contributor.authorHanson, H
dc.contributor.authorLoveday, C
dc.contributor.authorDolinsky, JS
dc.contributor.authorLaDuca, H
dc.contributor.authorRamus, SJ
dc.contributor.authorMenon, U
dc.contributor.authorRosenthal, AN
dc.contributor.authorJacobs, I
dc.contributor.authorGayther, SA
dc.contributor.authorDicks, E
dc.contributor.authorNevanlinna, H
dc.contributor.authorAittomäki, K
dc.contributor.authorPelttari, LM
dc.contributor.authorEhrencrona, H
dc.contributor.authorBorg, Å
dc.contributor.authorKvist, A
dc.contributor.authorRivera, B
dc.contributor.authorHansen, TVO
dc.contributor.authorDjursby, M
dc.contributor.authorLee, A
dc.contributor.authorDennis, J
dc.contributor.authorBowtell, DD
dc.contributor.authorTraficante, N
dc.contributor.authorDiez, O
dc.contributor.authorBalmaña, J
dc.contributor.authorGruber, SB
dc.contributor.authorChenevix-Trench, G
dc.contributor.authorInvestigators, K
dc.contributor.authorJensen, A
dc.contributor.authorKjær, SK
dc.contributor.authorHøgdall, E
dc.contributor.authorCastéra, L
dc.contributor.authorGarber, J
dc.contributor.authorJanavicius, R
dc.contributor.authorOsorio, A
dc.contributor.authorGolmard, L
dc.contributor.authorVega, A
dc.contributor.authorCouch, FJ
dc.contributor.authorRobson, M
dc.contributor.authorGronwald, J
dc.contributor.authorDomchek, SM
dc.contributor.authorCulver, JO
dc.contributor.authorde la Hoya, M
dc.contributor.authorEaston, DF
dc.contributor.authorFoulkes, WD
dc.contributor.authorTischkowitz, M
dc.contributor.authorMeindl, A
dc.contributor.authorSchmutzler, RK
dc.contributor.authorPharoah, PDP
dc.contributor.authorAntoniou, AC
dc.date.accessioned2020-07-09T12:08:46Z
dc.date.issued2020-12
dc.identifier.citationJournal of the National Cancer Institute, 2020, 112 (12), pp. 1242 - 1250
dc.identifier.issn0027-8874
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/3840
dc.identifier.eissn1460-2105
dc.identifier.doi10.1093/jnci/djaa030
dc.description.abstractBackground The purpose of this study was to estimate precise age-specific tubo-ovarian carcinoma (TOC) and breast cancer (BC) risks for carriers of pathogenic variants in RAD51C and RAD51D.Methods We analyzed data from 6178 families, 125 with pathogenic variants in RAD51C, and 6690 families, 60 with pathogenic variants in RAD51D. TOC and BC relative and cumulative risks were estimated using complex segregation analysis to model the cancer inheritance patterns in families while adjusting for the mode of ascertainment of each family. All statistical tests were two-sided.Results Pathogenic variants in both RAD51C and RAD51D were associated with TOC (RAD51C: relative risk [RR] = 7.55, 95% confidence interval [CI] = 5.60 to 10.19; P = 5 × 10-40; RAD51D: RR = 7.60, 95% CI = 5.61 to 10.30; P = 5 × 10-39) and BC (RAD51C: RR = 1.99, 95% CI = 1.39 to 2.85; P = 1.55 × 10-4; RAD51D: RR = 1.83, 95% CI = 1.24 to 2.72; P = .002). For both RAD51C and RAD51D, there was a suggestion that the TOC relative risks increased with age until around age 60 years and decreased thereafter. The estimated cumulative risks of developing TOC to age 80 years were 11% (95% CI = 6% to 21%) for RAD51C and 13% (95% CI = 7% to 23%) for RAD51D pathogenic variant carriers. The estimated cumulative risks of developing BC to 80 years were 21% (95% CI = 15% to 29%) for RAD51C and 20% (95% CI = 14% to 28%) for RAD51D pathogenic variant carriers. Both TOC and BC risks for RAD51C and RAD51D pathogenic variant carriers varied by cancer family history and could be as high as 32-36% for TOC, for carriers with two first-degree relatives diagnosed with TOC, or 44-46% for BC, for carriers with two first-degree relatives diagnosed with BC.Conclusions These estimates will facilitate the genetic counseling of RAD51C and RAD51D pathogenic variant carriers and justify the incorporation of RAD51C and RAD51D into cancer risk prediction models.
dc.formatPrint
dc.format.extent1242 - 1250
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.titleOvarian and Breast Cancer Risks Associated With Pathogenic Variants in RAD51C and RAD51D.
dc.typeJournal Article
dcterms.dateAccepted2020-02-25
rioxxterms.versionofrecord10.1093/jnci/djaa030
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
rioxxterms.licenseref.startdate2020-12
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfJournal of the National Cancer Institute
pubs.issue12
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/Cancer Genomics
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/Cancer Genomics
pubs.publication-statusPublished
pubs.volume112
pubs.embargo.termsNot known
icr.researchteamCancer Genomicsen_US
dc.contributor.icrauthorHoulston, Richarden


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