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Candidate genetic modifiers for breast and ovarian cancer risk in BRCA1 and BRCA2 mutation carriers

2015-01Journal article Open Access
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dc.contributor.authorPeterlongo, Paolo
dc.contributor.authorChang-Claude, Jenny
dc.contributor.authorMoysich, Kirsten B.
dc.contributor.authorRudolph, Anja
dc.contributor.authorSchmutzler, Rita K.
dc.contributor.authorSimard, Jacques
dc.contributor.authorSoucy, Penny
dc.contributor.authorEeles, Rosalind A.
dc.contributor.authorEaston, Douglas F.
dc.contributor.authorHamann, Ute
dc.contributor.authorWilkening, Stefan
dc.contributor.authorNevanlinna, Heli
dc.contributor.authorAittomaeki, Kristiina
dc.contributor.authorvan Os, Theo A. M.
dc.contributor.authorJensen, Uffe Birk
dc.contributor.authorMeijers-Heijboer, Hanne E. J.
dc.contributor.authorvan der Hout, Annemarie H.
dc.contributor.authorVreeswijk, Maaike P. G.
dc.contributor.authorRappaport, Christine
dc.contributor.authorHoogerbrugge, Nicoline
dc.contributor.authorArason, Adalgeir
dc.contributor.authorJonson, Lars
dc.contributor.authorAusems, Margreet G. E. M.
dc.contributor.authorvan der Baan, Frederieke H.
dc.contributor.authorvan Doorn, Helena C.
dc.contributor.authorCollee, J. Margriet
dc.contributor.authorOlah, Edith
dc.contributor.authorDiez, Orland
dc.contributor.authorLaitman, Yael
dc.contributor.authorBlanco, Ignacio
dc.contributor.authorLazaro, Conxi
dc.contributor.authorLose, Felicity
dc.contributor.authorOsorio, Ana
dc.contributor.authorKaulich, Daphne Geschwantler
dc.contributor.authorBrunet, Joan
dc.contributor.authorGiannini, Giuseppe
dc.contributor.authorChiquette, Jocelyne
dc.contributor.authorTeixeira, Manuel R.
dc.contributor.authorOlswold, Curtis
dc.contributor.authorCouch, Fergus J.
dc.contributor.authorLindor, Noralane M.
dc.contributor.authorWang, Xianshu
dc.contributor.authorWalker, Logan C.
dc.contributor.authorMartinez-Bouzas, Cristina
dc.contributor.authorSzabo, Csilla I.
dc.contributor.authorOffit, Kenneth
dc.contributor.authorvon Wachenfeldt, Anna
dc.contributor.authorPapi, Laura
dc.contributor.authorEhrencrona, Hans
dc.contributor.authorCorines, Marina
dc.contributor.authorBarwell, Julian
dc.contributor.authorPfeiler, Georg
dc.contributor.authorTea, Muy-Kheng M.
dc.contributor.authorPhelan, Catherine M.
dc.contributor.authorRhiem, Kerstin
dc.contributor.authorGreene, Mark H.
dc.contributor.authorMai, Phuong L.
dc.contributor.authorRennert, Gad
dc.contributor.authorMulligan, Anna Marie
dc.contributor.authorMartayan, Aline
dc.contributor.authorGlendon, Gord
dc.contributor.authorTchatchou, Sandrine
dc.contributor.authorMaia, Ana-Teresa
dc.contributor.authorWalker, Lisa
dc.contributor.authorMontagna, Marco
dc.contributor.authorBenitez, Javier
dc.contributor.authorAndrulis, Irene L.
dc.contributor.authorNiederacher, Dieter
dc.contributor.authorAskmalm, Marie Stenmark
dc.contributor.authorBorg, Ake
dc.contributor.authorKuchenbaecker, Karoline B.
dc.contributor.authorTibiletti, Maria Grazia
dc.contributor.authorMcGuffog, Lesley
dc.contributor.authorBarrowdale, Daniel
dc.contributor.authorHealey, Sue
dc.contributor.authorLee, Andrew
dc.contributor.authorConway, Edye E.
dc.contributor.authorIzatt, Louise
dc.contributor.authorPharoah, Paul D. P.
dc.contributor.authorChenevix-Trench, Georgia
dc.contributor.authorAntoniou, Antonis C.
dc.contributor.authorSteinemann, Doris
dc.contributor.authorMatricardi, Laura
dc.contributor.authorRadice, Paolo
dc.contributor.authorFriedman, Eitan
dc.contributor.authorLubinski, Jan
dc.contributor.authorJakubowska, Anna
dc.contributor.authorBlazer, Kathleen R.
dc.contributor.authorGarcia, Encarna B. Gomez
dc.contributor.authorOlopade, Olufunmilayo I.
dc.contributor.authorSide, Lucy E.
dc.contributor.authorNussbaum, Robert L.
dc.contributor.authorNathanson, Katherine L.
dc.contributor.authorDomchek, Susan M.
dc.contributor.authorRebbeck, Timothy R.
dc.contributor.authorVratimos, Athanassios
dc.contributor.authorPlendl, Hansjoerg
dc.contributor.authorArun, Banu K.
dc.contributor.authorPorteous, Mary E.
dc.contributor.authorKarlan, Beth Y.
dc.contributor.authorOrsulic, Sandra
dc.contributor.authorLester, Jenny
dc.contributor.authorChung, Wendy K.
dc.contributor.authorKennedy, M. John
dc.contributor.authorMiron, Alex
dc.contributor.authorSouthey, Melissa C.
dc.contributor.authorGoldgar, David E.
dc.contributor.authorFostira, Florentia
dc.contributor.authorBuys, Saundra S.
dc.contributor.authorWeitzel, Jeffrey N.
dc.contributor.authorJanavicius, Ramunas
dc.contributor.authorKast, Karin
dc.contributor.authorDorfling, Cecilia M.
dc.contributor.authorvan Rensburg, Elizabeth J.
dc.contributor.authorDing, Yuan Chun
dc.contributor.authorNeuhausen, Susan L.
dc.contributor.authorRogers, Mark T.
dc.contributor.authorHansen, Thomas V. O.
dc.contributor.authorGerdes, Anne-Marie
dc.contributor.authorArnold, Norbert
dc.contributor.authorGarber, Judy E.
dc.contributor.authorEjlertsen, Bent
dc.contributor.authorFeliubadalo, Lidia
dc.contributor.authorManoukian, Siranoush
dc.contributor.authorPeissel, Bernard
dc.contributor.authorZaffaroni, Daniela
dc.contributor.authorScuvera, Giulietta
dc.contributor.authorBarile, Monica
dc.contributor.authorFicarazzi, Filomena
dc.contributor.authorDitsch, Nina
dc.contributor.authorMariette, Frederique
dc.contributor.authorFortuzzi, Stefano
dc.contributor.authorMorrison, Patrick J.
dc.contributor.authorCybulski, Cezary
dc.contributor.authorPlatte, Radka
dc.contributor.authorViel, Alessandra
dc.contributor.authorJacobs, Lauren
dc.contributor.authorDonaldson, Alan
dc.contributor.authorBrewer, Carole
dc.contributor.authorFoo, Claire
dc.contributor.authorEvans, D. Gareth R.
dc.contributor.authorFrost, Debra
dc.contributor.authorEccles, Diana
dc.contributor.authorBrady, Angela
dc.contributor.authorGronwald, Jacek
dc.contributor.authorCook, Jackie
dc.contributor.authorTischkowitz, Marc
dc.contributor.authorVaron-Mateeva, Raymonda
dc.contributor.authorRobson, Mark E.
dc.contributor.authorWappenschmidt, Barbara
dc.contributor.authorAdlard, Julian
dc.contributor.authorToland, Amanda Ewart
dc.contributor.authorDavidson, Rosemarie
dc.contributor.authorHodgson, Shirley V.
dc.contributor.authorEllis, Steve
dc.contributor.authorSpurdle, Amanda B.
dc.contributor.authorCole, Trevor
dc.contributor.authorGodwin, Andrew K.
dc.contributor.authorClaes, Kathleen
dc.contributor.authorVan Maerken, Tom
dc.contributor.authorZhang, Liying
dc.contributor.authorMeindl, Alfons
dc.contributor.authorGehrig, Andrea
dc.contributor.authorSutter, Christian
dc.contributor.authorBojesen, Anders
dc.contributor.authorWang-Gohrke, Shan
dc.contributor.authorDurda, Katarzyna
dc.contributor.authorEngel, Christoph
dc.contributor.authorChen, Bowang
dc.contributor.authorBressac-de Paillerets, Brigitte
dc.contributor.authorBuecher, Bruno
dc.contributor.authorDelnatte, Capucine
dc.contributor.authorJoseph, Vijai
dc.contributor.authorHoudayer, Claude
dc.contributor.authorStoppa-Lyonnet, Dominique
dc.contributor.authorDamiola, Francesca
dc.contributor.authorCoupier, Isabelle
dc.contributor.authorJaworska-Bieniek, Katarzyna
dc.contributor.authorPedersen, Inge Sokilde
dc.contributor.authorBarjhoux, Laure
dc.contributor.authorVenat-Bouvet, Laurence
dc.contributor.authorGolmard, Lisa
dc.contributor.authorRookus, Matti A.
dc.contributor.authorBoutry-Kryza, Nadia
dc.contributor.authorBerger, Andreas
dc.contributor.authorSinilnikova, Olga M.
dc.contributor.authorCaron, Olivier
dc.contributor.authorPujol, Pascal
dc.contributor.authorSukiennicki, Grzegorz
dc.contributor.authorMazoyer, Sylvie
dc.contributor.authorBelotti, Muriel
dc.contributor.authorThomassen, Mads
dc.contributor.authorPiedmonte, Marion
dc.contributor.authorFriedlander, Michael L.
dc.contributor.authorRodriguez, Gustavo C.
dc.contributor.authorCopeland, Larry J.
dc.contributor.authorSinger, Christian F.
dc.contributor.authorSchmidt, MarjankaK.
dc.contributor.authorde la Hoya, Miguel
dc.contributor.authorRantala, Johanna
dc.contributor.authorPerez Segura, Pedro
dc.date.accessioned2018-12-07T14:53:08Z
dc.date.available2018-12-07T14:53:08Z
dc.date.issued2015-01
dc.description.abstractBackground: BRCA1 and BRCA2 mutation carriers are at substantially increased risk for developing breast and ovarian cancer. The incomplete penetrance coupled with the variable age at diagnosis in carriers of the same mutation suggests the existence of genetic and nongenetic modifying factors. In this study, we evaluated the putative role of variants in many candidate modifier genes. Methods: Genotyping data from 15,252 BRCA1 and 8,211 BRCA2 mutation carriers, for known variants (n = 3,248) located within or around 445 candidate genes, were available through the iCOGS custom-designed array. Breast and ovarian cancer association analysis was performed within a retrospective cohort approach. Results: The observed P values of association ranged between 0.005 and 1.000. None of the variants was significantly associated with breast or ovarian cancer risk in either BRCA1 or BRCA2 mutation carriers, after multiple testing adjustments. Conclusion: There is little evidence that any of the evaluated candidate variants act as modifiers of breast and/or ovarian cancer risk in BRCA1 or BRCA2 mutation carriers. Impact: Genome-wide association studies have been more successful at identifying genetic modifiers of BRCA1/2 penetrance than candidate gene studies. (C)2014 AACR.
dc.description.sponsorshipEuropean Community (COGS) [223175, HEALTH-F2-2009-223175]; Cancer Research UK [C1287/A10118, C1287/A 10710, C12292/A11174, C1281/A12014, C5047/A8384, C5047/ A15007, C5047/A10692, C1287/A16563, C1287/A17523, C5047/A8385]; NIH [CA128978, R01-CA102776, R01CA083855]; Post-Cancer GWAS initiative [1U19CA148537, 1U19 CA148065, 1U19 CA148112]; Department of Defence [W81XWH-10-1-0341]; Canadian Institutes of Health Research (CIHR) for the CIHR Team in Familial Risks of Breast Cancer; Komen Foundation; Breast Cancer Research Foundation; Ovarian Cancer Research Fund; National Cancer Institute [UM1 CA164920, RC4CA153828]; Research Council of Lithuania [LIG-07/2012]; Cancer Association of South Africa (CANSA); Spanish Association against Cancer [AECC08, RTICC 06/0020/1060, FISPI12/00070]; Mutua Madrilena Foundation (FMMA); City of Hope Clinical Cancer Genetics Community Research Network and the Hereditary Cancer Research Registry (COH-CCGCRN); Fondazione IRCCS Istituto Nazionale dei Tumori; DKFZ; NIHR grant to the Biomedical Research Centre, Manchester; NIHR grant to the Biomedical Research Centre at The Institute of Cancer Research; Royal Marsden NHS Foundation Trust; German Cancer Aid [109078]; Center for Molecular Medicine Cologne (CMMC); Ligue National Contre le Cancer; Association "Le cancer du sein, parlons-en!" Award; Canadian Institutes of Health Research for the "CIHR Team in Familial Risks of Breast Cancer" program; Helsinki University Central Hospital Research Fund, Academy of Finland [266528]; Finnish Cancer Society and the Sigrid Juselius Foundation; Dutch Cancer Society [NKI1998-1854, NKI2004-3088, NKI2007-3756]; Netherlands Organization of Scientific Research [NWO 91109024]; Pink Ribbon [110005]; BBMRI [NWO 184.021.007/CP46]; Hungarian Research Grants [KTIA OTKA CK-80745, OTKA K-112228]; Asociacion Espanola Contra el Cancer; Spanish Health Research Fund; Carlos III Health Institute; Catalan Health Institute and Autonomous Government of Catalonia [ISCIIIRETIC RD06/0020/1051, RD12/0036/008, PI10/01422, PI10/00748, PI13/00285, 2009SGR290]; Icelandic Association "Walking for Breast Cancer Research"; Landspitali University Hospital Research Fund; Ministero della Salute; Istituto Oncologico Veneto; National Breast Cancer Foundation; National Health and Medical Research Council (NHMRC); Queensland Cancer Fund; Cancer Councils of New South Wales, Victoria, Tasmania and South Australia; Cancer Foundation of Western Australia; NCI Specialized Program of Research Excellence (SPORE) in Breast Cancer [CA116201]; U.S. Department of Defence Ovarian Cancer Idea award [W81XWH-10-1-0341]; David and Margaret T. Grohne Family Foundation; Ting Tsung and Wei Fong Chao Foundation; Robert and Kate Niehaus Clinical Cancer Genetics Initiative; Ohio State University Comprehensive Cancer Center; Swedish Cancer Society; Women's Cancer Program (WCP) at the Samuel Oschin Comprehensive Cancer Institute - American Cancer Society Early Detection Professorship [SIOP-06-258-01-COUN]; NEYE Foundation; European Union (European Social Fund - ESF); Greek national funds through the Operational Program "Education and Lifelong Learning" of the National Strategic Reference Framework (NSRF) - Research Funding Program of the General Secretariat for Research Technology:; University of Kansas Cancer Center [P30 CA168524]; Kansas Bioscience Authority Eminent Scholar Program; National Cancer Institute grants to the Gynecologic Oncology Group (GOG) Administrative Office and Tissue Bank [CA 27469]; GOG Statistical and Data Center [CA 37517]; NCI's Community Clinical Oncology Program (CCOP) grant [CA 101165]; Canadian Breast Cancer Research Alliance-grant [019511]; Ministry of Economic Development, Innovation and Export Trade - grant [PSR-SIIRI-701]; Israel Cancer Association; Israeli Inherited Breast Cancer Consortium; Susan G. Komen Foundation; Basser Research Center; ISCIII [RD12/00369/0006]; European Regional Development funds, Spain; Morris and Horowitz Families Endowed Professorship; Chancellors Distinguished Chair in Biomedical Sciences Professorship; Intramural Research Program of the US National Cancer Institute; NIH; Westat, Inc; [PBZ_KBN_122/P05/2004]; [1R01 CA149429-01]; [5U01CA113916]; [R01CA140323]; [NO2-CP-11019- 50]; [N02-CP-65504]; Associazione Italiana per la Ricerca sul Cancro; Cancer Research UK [11174, 10119, 17528, 17523, 15007, 10124, 10118, 16561, 16563]; National Institute for Health Research [NF-SI-0510-10096]
dc.description.versioninfo:eu-repo/semantics/publishedVersion
dc.identifier.doi10.1158/1055-9965.EPI-14-0532
dc.identifier.issn1055-9965
dc.identifier.issn1538-7755
dc.identifier.urihttp://hdl.handle.net/10400.1/11362
dc.language.isoeng
dc.peerreviewedyes
dc.publisherAmerican Association for Cancer Research
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectAssociation
dc.titleCandidate genetic modifiers for breast and ovarian cancer risk in BRCA1 and BRCA2 mutation carriers
dc.typejournal article
dspace.entity.typePublication
oaire.citation.endPage316
oaire.citation.issue1
oaire.citation.startPage308
oaire.citation.titleCancer Epidemiology, Biomarkers and Prevention
oaire.citation.volume24
person.familyNameMaia
person.givenNameAna-Teresa
person.identifier.orcid0000-0002-0454-9207
person.identifier.ridF-4404-2012
person.identifier.scopus-author-id14319300100
rcaap.rightsopenAccess
rcaap.typearticle
relation.isAuthorOfPublication229d470e-6eb8-4144-a68a-5e0d5bec8a2c
relation.isAuthorOfPublication.latestForDiscovery229d470e-6eb8-4144-a68a-5e0d5bec8a2c

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