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Association of the CHEK2 c.1100delC variant, radiotherapy, and systemic treatment with contralateral breast cancer risk and breast cancer-specific survival

dc.contributor.authorMorra, A.*
dc.contributor.authorSchreurs, M.A.C.*
dc.contributor.authorAndrulis, I.L.*
dc.contributor.authorAnton-Culver, H.*
dc.contributor.authorAugustinsson, A.*
dc.contributor.authorBeckmann, M.W.*
dc.contributor.authorBehrens, S.*
dc.contributor.authorBojesen, S.E.*
dc.contributor.authorBolla, M.K.*
dc.contributor.authorBrauch, H.*
dc.contributor.authorBroeks, A.*
dc.contributor.authorBuys, S.S.*
dc.contributor.authorCamp, N.J.*
dc.contributor.authorCastelao Fernández, José Esteban *
dc.contributor.authorCessna, M.H.*
dc.contributor.authorChang-Claude, J.*
dc.contributor.authorChung, W.K.*
dc.contributor.authorSahlberg, K.K.*
dc.contributor.authorBørresen-Dale, A.-L.*
dc.contributor.authorGram, I.T.*
dc.contributor.authorOlsen, K.S.*
dc.contributor.authorEngebråten, O.*
dc.contributor.authorNaume, B.*
dc.contributor.authorGeisler, J.*
dc.contributor.authorGrenaker Alnæs, G.I.*
dc.contributor.authorColonna, S.V.*
dc.contributor.authorCouch, F.J.*
dc.contributor.authorCox, A.*
dc.contributor.authorCross, S.S.*
dc.contributor.authorCzene, K.*
dc.contributor.authorDaly, M.B.*
dc.contributor.authorDennis, J.*
dc.contributor.authorDevilee, P.*
dc.contributor.authorDörk, T.*
dc.contributor.authorDunning, A.M.*
dc.contributor.authorDwek, M.*
dc.contributor.authorEaston, D.F.*
dc.contributor.authorEccles, D.M.*
dc.contributor.authorEriksson, M.*
dc.contributor.authorEvans, D.G.*
dc.contributor.authorFasching, P.A.*
dc.contributor.authorFehm, T.N.*
dc.contributor.authorFigueroa, J.D.*
dc.contributor.authorFlyger, H.*
dc.contributor.authorGabrielson, M.*
dc.contributor.authorGago Dominguez, Manuela*
dc.contributor.authorGarcía-Closas, M.*
dc.contributor.authorGarcía-Sáenz, J.A.*
dc.contributor.authorGenkinger, J.*
dc.contributor.authorGrassmann, F.*
dc.contributor.authorGündert, M.*
dc.contributor.authorHahnen, E.*
dc.contributor.authorHaiman, C.A.*
dc.contributor.authorHamann, U.*
dc.contributor.authorHarrington, P.A.*
dc.contributor.authorHartikainen, J.M.*
dc.contributor.authorHoppe, R.*
dc.contributor.authorHopper, J.L.*
dc.contributor.authorHoulston, R.S.*
dc.contributor.authorHowell, A.*
dc.contributor.authorClarke, C.*
dc.contributor.authorMarsh, D.*
dc.contributor.authorScott, R.*
dc.contributor.authorBaxter, R.*
dc.contributor.authorYip, D.*
dc.contributor.authorCarpenter, J.*
dc.contributor.authorDavis, A.*
dc.contributor.authorPathmanathan, N.*
dc.contributor.authorSimpson, P.*
dc.contributor.authorGraham, J.D.*
dc.contributor.authorSachchithananthan, M.*
dc.contributor.authorAmor, D.*
dc.contributor.authorAndrews, L.*
dc.contributor.authorAntill, Y.*
dc.contributor.authorBalleine, R.*
dc.contributor.authorBeesley, J.*
dc.contributor.authorBennett, I.*
dc.contributor.authorBogwitz, M.*
dc.contributor.authorBotes, L.*
dc.contributor.authorBrennan, M.*
dc.contributor.authorBrown, M.*
dc.contributor.authorBuckley, M.*
dc.contributor.authorBurke, J.*
dc.contributor.authorButow, P.*
dc.contributor.authorCaldon, L.*
dc.contributor.authorCampbell, I.*
dc.contributor.authorCao, M.*
dc.contributor.authorChakrabarti, A.*
dc.contributor.authorChauhan, D.*
dc.contributor.authorChauhan, M.*
dc.contributor.authorChenevix-Trench, G.*
dc.contributor.authorChristian, A.*
dc.contributor.authorCohen, P.*
dc.contributor.authorColley, A.*
dc.contributor.authorCrook, A.*
dc.contributor.authorCui, J.*
dc.contributor.authorCourtney, E.*
dc.contributor.authorCummings, M.*
dc.contributor.authorDawson, S.-J.*
dc.contributor.authorDeFazio, A.*
dc.contributor.authorDelatycki, M.*
dc.contributor.authorDickson, R.*
dc.contributor.authorDixon, J.*
dc.contributor.authorEdkins, T.*
dc.contributor.authorEdwards, S.*
dc.contributor.authorFarshid, G.*
dc.contributor.authorFellows, A.*
dc.contributor.authorFenton, G.*
dc.contributor.authorField, M.*
dc.contributor.authorFlanagan, J.*
dc.contributor.authorFong, P.*
dc.contributor.authorForrest, L.*
dc.contributor.authorFox, S.*
dc.contributor.authorFrench, J.*
dc.contributor.authorFriedlander, M.*
dc.contributor.authorGaff, C.*
dc.contributor.authorGattas, M.*
dc.contributor.authorGeorge, P.*
dc.contributor.authorGreening, S.*
dc.contributor.authorHarris, M.*
dc.contributor.authorHart, S.*
dc.contributor.authorHayward, N.*
dc.contributor.authorHopper, J.*
dc.contributor.authorHoskins, C.*
dc.contributor.authorHunt, C.*
dc.contributor.authorJames, P.*
dc.contributor.authorJenkins, M.*
dc.contributor.authorKidd, A.*
dc.contributor.authorKirk, J.*
dc.contributor.authorKoehler, J.*
dc.contributor.authorKollias, J.*
dc.contributor.authorLakhani, S.*
dc.contributor.authorLawrence, M.*
dc.contributor.authorLee, J.*
dc.contributor.authorLi, S.*
dc.contributor.authorLindeman, G.*
dc.contributor.authorLipton, L.*
dc.contributor.authorLobb, L.*
dc.contributor.authorLoi, S.*
dc.contributor.authorMann, G.*
dc.contributor.authorMarsh, D.*
dc.contributor.authorMcLachlan, S.A.*
dc.contributor.authorMeiser, B.*
dc.contributor.authorMilne, R.*
dc.contributor.authorNightingale, S.*
dc.contributor.authorO'Connell, S.*
dc.contributor.authorO'Sullivan, S.*
dc.contributor.authorOrtega, D.G.*
dc.contributor.authorPachter, N.*
dc.contributor.authorPang, J.-M.*
dc.contributor.authorPathak, G.*
dc.contributor.authorPatterson, B.*
dc.contributor.authorPearn, A.*
dc.contributor.authorPhillips, K.*
dc.contributor.authorPieper, E.*
dc.contributor.authorRamus, S.*
dc.contributor.authorRickard, E.*
dc.contributor.authorRobinson, B.*
dc.contributor.authorSaleh, M.*
dc.contributor.authorSkandarajah, A.*
dc.contributor.authorSalisbury, E.*
dc.contributor.authorSaunders, C.*
dc.contributor.authorSaunus, J.*
dc.contributor.authorScott, R.*
dc.contributor.authorScott, C.*
dc.contributor.authorSexton, A.*
dc.contributor.authorShelling, A.*
dc.contributor.authorSimpson, P.*
dc.contributor.authorSouthey, M.*
dc.contributor.authorSpurdle, A.*
dc.contributor.authorTaylor, J.*
dc.contributor.authorTaylor, R.*
dc.contributor.authorThorne, H.*
dc.contributor.authorTrainer, A.*
dc.contributor.authorTucker, K.*
dc.contributor.authorVisvader, J.*
dc.contributor.authorWalker, L.*
dc.contributor.authorWilliams, R.*
dc.contributor.authorWinship, I.*
dc.contributor.authorYoung, M.A.*
dc.contributor.authorZaheed, M.*
dc.contributor.authorJakubowska, A.*
dc.contributor.authorJanni, W.*
dc.contributor.authorJernström, H.*
dc.contributor.authorJohn, E.M.*
dc.contributor.authorJohnson, N.*
dc.contributor.authorJones, M.E.*
dc.contributor.authorKristensen, V.N.*
dc.contributor.authorKurian, A.W.*
dc.contributor.authorLambrechts, D.*
dc.contributor.authorLe Marchand, L.*
dc.contributor.authorLindblom, A.*
dc.contributor.authorLubi?ski, J.*
dc.contributor.authorLux, M.P.*
dc.contributor.authorMannermaa, A.*
dc.contributor.authorMavroudis, D.*
dc.contributor.authorMulligan, A.M.*
dc.contributor.authorMuranen, T.A.*
dc.contributor.authorNevanlinna, H.*
dc.contributor.authorNevelsteen, I.*
dc.contributor.authorNeven, P.*
dc.contributor.authorNewman, W.G.*
dc.contributor.authorObi, N.*
dc.contributor.authorOffit, K.*
dc.contributor.authorOlshan, A.F.*
dc.contributor.authorPark-Simon, T.-W.*
dc.contributor.authorPatel, A.V.*
dc.contributor.authorPeterlongo, P.*
dc.contributor.authorPhillips, K.-A.*
dc.contributor.authorPlaseska-Karanfilska, D.*
dc.contributor.authorPolley, E.C.*
dc.contributor.authorPresneau, N.*
dc.contributor.authorPylkäs, K.*
dc.contributor.authorRack, B.*
dc.contributor.authorRadice, P.*
dc.contributor.authorRashid, M.U.*
dc.contributor.authorRhenius, V.*
dc.contributor.authorRobson, M.*
dc.contributor.authorRomero, A.*
dc.contributor.authorSaloustros, E.*
dc.contributor.authorSawyer, E.J.*
dc.contributor.authorSchmutzler, R.K.*
dc.contributor.authorSchuetze, S.*
dc.contributor.authorScott, C.*
dc.contributor.authorShah, M.*
dc.contributor.authorSmichkoska, S.*
dc.contributor.authorSouthey, M.C.*
dc.contributor.authorTapper, W.J.*
dc.contributor.authorTeras, L.R.*
dc.contributor.authorTollenaar, R.A.E.M.*
dc.contributor.authorTomczyk, K.*
dc.contributor.authorTomlinson, I.*
dc.contributor.authorTroester, M.A.*
dc.contributor.authorVachon, C.M.*
dc.contributor.authorvan Veen, E.M.*
dc.contributor.authorWang, Q.*
dc.contributor.authorWendt, C.*
dc.contributor.authorWildiers, H.*
dc.contributor.authorWinqvist, R.*
dc.contributor.authorZiogas, A.*
dc.contributor.authorHall, P.*
dc.contributor.authorPharoah, P.D.P.*
dc.contributor.authorAdank, M.A.*
dc.contributor.authorHollestelle, A.*
dc.contributor.authorSchmidt, M.K.*
dc.contributor.authorHooning, M.J.*
dc.date.accessioned2025-09-08T09:19:04Z
dc.date.available2025-09-08T09:19:04Z
dc.date.issued2023
dc.identifier.citationMorra A, Schreurs MAC, Andrulis IL, Anton-Culver H, Augustinsson A, Beckmann MW, et al. Association of the CHEK2 c.1100delC variant, radiotherapy, and systemic treatment with contralateral breast cancer risk and breast cancer-specific survival. Cancer Medicine. 2023;12(15):16142-62.
dc.identifier.issn2045-7634
dc.identifier.otherhttps://portalcientifico.sergas.gal//documentos/65c35cbbd2edca1267d6a0f9
dc.identifier.urihttp://hdl.handle.net/20.500.11940/21123
dc.description.abstractBackground: Breast cancer (BC) patients with a germline CHEK2 c.1100delC variant have an increased risk of contralateral BC (CBC) and worse BC-specific survival (BCSS) compared to non-carriers. Aim: To assessed the associations of CHEK2 c.1100delC, radiotherapy, and systemic treatment with CBC risk and BCSS. Methods: Analyses were based on 82,701 women diagnosed with a first primary invasive BC including 963 CHEK2 c.1100delC carriers; median follow-up was 9.1 years. Differential associations with treatment by CHEK2 c.1100delC status were tested by including interaction terms in a multivariable Cox regression model. A multi-state model was used for further insight into the relation between CHEK2 c.1100delC status, treatment, CBC risk and death. Results: There was no evidence for differential associations of therapy with CBC risk by CHEK2 c.1100delC status. The strongest association with reduced CBC risk was observed for the combination of chemotherapy and endocrine therapy [HR (95% CI): 0.66 (0.55-0.78)]. No association was observed with radiotherapy. Results from the multi-state model showed shorter BCSS for CHEK2 c.1100delC carriers versus non-carriers also after accounting for CBC occurrence [HR (95% CI): 1.30 (1.09-1.56)]. Conclusion: Systemic therapy was associated with reduced CBC risk irrespective of CHEK2 c.1100delC status. Moreover, CHEK2 c.1100delC carriers had shorter BCSS, which appears not to be fully explained by their CBC risk.
dc.description.sponsorshipCanadian Institutes of Health Research, Grant/Award Number: GPH-129344; Cancer Research UK, Grant/Award Number: C12292/A11174, C1281/A12014, C1287/A10118, C1287/A10710, C1287/A16563, C5047/A10692, C5047/A15007, C5047/A8384 and C8197/A16565; US Department of Defence, Grant/Award Number: W81XWH-10-1-0341; European Union's Horizon 2020 Research and Innovation Programme, Grant/Award Number: 633784 and 634935; Fondation du cancer du sein du Quebec; FP7 Ideas: European Research Council, Grant/Award Number: HEALTH-F2-2009-223175; Genome Canada; Genome Quebec; Government of Canada; National Institutes of Health, Grant/Award Number: CA128978 and U19 CA148065; Post-Cancer GWAS initiative, Grant/Award Number: 1U19 CA148065, 1U19 CA148112 - the GAME-ON initiative and 1U19 CA148537; Wellcome Trust, Grant/Award Number: v203477/Z/16/Z
dc.languageeng
dc.rightsAttribution 4.0 International (CC BY 4.0)*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subject.meshFemale *
dc.subject.meshHumans *
dc.subject.meshBreast Neoplasms *
dc.subject.meshCheckpoint Kinase 2 *
dc.subject.meshGenetic Predisposition to Disease *
dc.subject.meshGerm-Line Mutation *
dc.subject.meshHeterozygote *
dc.subject.meshProportional Hazards Models *
dc.titleAssociation of the CHEK2 c.1100delC variant, radiotherapy, and systemic treatment with contralateral breast cancer risk and breast cancer-specific survival
dc.typeArtigo
dc.authorsophosMorra, A.; Schreurs, M.A.C.; Andrulis, I.L.; Anton-Culver, H.; Augustinsson, A.; Beckmann, M.W.; Behrens, S.; Bojesen, S.E.; Bolla, M.K.; Brauch, H.; Broeks, A.; Buys, S.S.; Camp, N.J.; Castelao, J.E.; Cessna, M.H.; Chang-Claude, J.; Chung, W.K.; Sahlberg, K.K.; Børresen-Dale, A.-L.; Gram, I.T.; Olsen, K.S.; Engebråten, O.; Naume, B.; Geisler, J.; Grenaker Alnæs, G.I.; Colonna, S.V.; Couch, F.J.; Cox, A.; Cross, S.S.; Czene, K.; Daly, M.B.; Dennis, J.; Devilee, P.; Dörk, T.; Dunning, A.M.; Dwek, M.; Easton, D.F.; Eccles, D.M.; Eriksson, M.; Evans, D.G.; Fasching, P.A.; Fehm, T.N.; Figueroa, J.D.; Flyger, H.; Gabrielson, M.; Gago-Dominguez, M.; García-Closas, M.; García-Sáenz, J.A.; Genkinger, J.; Grassmann, F.; Gündert, M.; Hahnen, E.; Haiman, C.A.; Hamann, U.; Harrington, P.A.; Hartikainen, J.M.; Hoppe, R.; Hopper, J.L.; Houlston, R.S.; Howell, A.; Clarke, C.; Marsh, D.; Scott, R.; Baxter, R.; Yip, D.; Carpenter, J.; Davis, A.; Pathmanathan, N.; Simpson, P.; Graham, J.D.; Sachchithananthan, M.; Amor, D.; Andrews, L.; Antill, Y.; Balleine, R.; Beesley, J.; Bennett, I.; Bogwitz, M.; Botes, L.; Brennan, M.; Brown, M.; Buckley, M.; Burke, J.; Butow, P.; Caldon, L.; Campbell, I.; Cao, M.; Chakrabarti, A.; Chauhan, D.; Chauhan, M.; Chenevix-Trench, G.; Christian, A.; Cohen, P.; Colley, A.; Crook, A.; Cui, J.; Courtney, E.; Cummings, M.; Dawson, S.-J.; DeFazio, A.; Delatycki, M.; Dickson, R.; Dixon, J.; Edkins, T.; Edwards, S.; Farshid, G.; Fellows, A.; Fenton, G.; Field, M.; Flanagan, J.; Fong, P.; Forrest, L.; Fox, S.; French, J.; Friedlander, M.; Gaff, C.; Gattas, M.; George, P.; Greening, S.; Harris, M.; Hart, S.; Hayward, N.; Hopper, J.; Hoskins, C.; Hunt, C.; James, P.; Jenkins, M.; Kidd, A.; Kirk, J.; Koehler, J.; Kollias, J.; Lakhani, S.; Lawrence, M.; Lee, J.; Li, S.; Lindeman, G.; Lipton, L.; Lobb, L.; Loi, S.; Mann, G.; Marsh, D.; McLachlan, S.A.; Meiser, B.; Milne, R.; Nightingale, S.; O'Connell, S.; O'Sullivan, S.; Ortega, D.G.; Pachter, N.; Pang, J.-M.; Pathak, G.; Patterson, B.; Pearn, A.; Phillips, K.; Pieper, E.; Ramus, S.; Rickard, E.; Robinson, B.; Saleh, M.; Skandarajah, A.; Salisbury, E.; Saunders, C.; Saunus, J.; Scott, R.; Scott, C.; Sexton, A.; Shelling, A.; Simpson, P.; Southey, M.; Spurdle, A.; Taylor, J.; Taylor, R.; Thorne, H.; Trainer, A.; Tucker, K.; Visvader, J.; Walker, L.; Williams, R.; Winship, I.; Young, M.A.; Zaheed, M.; Jakubowska, A.; Janni, W.; Jernström, H.; John, E.M.; Johnson, N.; Jones, M.E.; Kristensen, V.N.; Kurian, A.W.; Lambrechts, D.; Le Marchand, L.; Lindblom, A.; Lubi?ski, J.; Lux, M.P.; Mannermaa, A.; Mavroudis, D.; Mulligan, A.M.; Muranen, T.A.; Nevanlinna, H.; Nevelsteen, I.; Neven, P.; Newman, W.G.; Obi, N.; Offit, K.; Olshan, A.F.; Park-Simon, T.-W.; Patel, A.V.; Peterlongo, P.; Phillips, K.-A.; Plaseska-Karanfilska, D.; Polley, E.C.; Presneau, N.; Pylkäs, K.; Rack, B.; Radice, P.; Rashid, M.U.; Rhenius, V.; Robson, M.; Romero, A.; Saloustros, E.; Sawyer, E.J.; Schmutzler, R.K.; Schuetze, S.; Scott, C.; Shah, M.; Smichkoska, S.; Southey, M.C.; Tapper, W.J.; Teras, L.R.; Tollenaar, R.A.E.M.; Tomczyk, K.; Tomlinson, I.; Troester, M.A.; Vachon, C.M.; van Veen, E.M.; Wang, Q.; Wendt, C.; Wildiers, H.; Winqvist, R.; Ziogas, A.; Hall, P.; Pharoah, P.D.P.; Adank, M.A.; Hollestelle, A.; Schmidt, M.K.; Hooning, M.J.
dc.identifier.doi10.1002/cam4.6272
dc.identifier.sophos65c35cbbd2edca1267d6a0f9
dc.issue.number15
dc.journal.titleCancer Medicine*
dc.organizationServizo Galego de Saúde::Áreas Sanitarias (A.S.) - Complexo Hospitalario Universitario de Vigo
dc.organizationServizo Galego de Saúde::Áreas Sanitarias (A.S.) - Instituto de Investigación Sanitaria de Santiago de Compostela (IDIS)::Xenética
dc.page.initial16142
dc.page.final16162
dc.relation.projectIDCanadian Institutes of Health Research
dc.relation.projectIDCancer Research UK
dc.relation.projectIDUS Department of Defence
dc.relation.projectIDEuropean Union
dc.relation.projectIDFondation du cancer du sein du Quebec
dc.relation.projectIDFP7 Ideas: European Research Council
dc.relation.projectIDGenome Canada
dc.relation.projectIDGenome Quebec
dc.relation.projectIDGovernment of Canada
dc.relation.projectIDNational Institutes of Health
dc.relation.projectIDPost-Cancer GWAS initiative
dc.relation.projectIDWellcome Trust
dc.relation.projectID[GPH-129344]
dc.relation.projectID[C12292/A11174]
dc.relation.projectID[C1281/A12014]
dc.relation.projectID[C1287/A10118]
dc.relation.projectID[C1287/A10710]
dc.relation.projectID[C1287/A16563]
dc.relation.projectID[C5047/A10692]
dc.relation.projectID[C5047/A15007]
dc.relation.projectID[C5047/A8384]
dc.relation.projectID[C8197/A16565]
dc.relation.projectID[W81XWH-10-1-0341]
dc.relation.projectID[633784]
dc.relation.projectID[634935]
dc.relation.projectID[HEALTH-F2-2009-223175]
dc.relation.projectID[CA128978]
dc.relation.projectID[U19 CA148065]
dc.relation.projectID[1U19 CA148065]
dc.relation.projectID[1U19 CA148112]
dc.relation.projectID[1U19 CA148537]
dc.relation.projectID[v203477/Z/16/Z]
dc.relation.projectIDCancer Research UK [23382] Funding Source: researchfish
dc.relation.projectIDMedical Research Council [G1000143, MR/M012190/1] Funding Source: researchfish
dc.relation.publisherversionhttps://doi.org/10.1002/cam4.6272
dc.rights.accessRightsopenAccess*
dc.subject.keywordAS Vigo
dc.subject.keywordCHUVI
dc.subject.keywordAS Santiago
dc.subject.keywordIDIS
dc.typefidesArtículo Científico (incluye Original, Original breve, Revisión Sistemática y Meta-análisis)
dc.typesophosArtículo Original
dc.volume.number12


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