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RESEARCH PRODUCT

Ovarian cancer susceptibility alleles and risk of ovarian cancer in BRCA1 and BRCA2 mutation carriers

Susan J. RamusAntonis C. AntoniouKaroline B. KuchenbaeckerSoucy PennyBeesley JonathanChen XiaoqingMcguffog LesleyOlga M. SinilnikovaHealey SueBarrowdale DanielLee AndrewThomassen Mads Anne Marie GerdesTorben A. KruseUffe Birk Jensen Anne Bine SkytteMaria A. CaligoLiljegren AnnelieLindblom AnnikaOlsson HakanKristoffersson Ulf Marie Stenmark AskmalmB. Swe Brca MelinBrca SweSusan M. DomchekSm DomchekKatherine L. NathansonTimothy R. RebbeckJakubowska AnnaLubinski JanJaworska KatarzynaDurda KatarzynaZłowocka ElzbietaGronwald JacekTomasz HuzarskiTomasz ByrskiCybulski Cezary Aleksandra Toloczko GrabarekOsorio AnaBenitez JavierMercedes DuránMaria-isabel TejadaHamann UteRookus MattiFlora E. Van LeeuwenCora M. AalfsHanne E. J. Meijers HeijboerChristi J. Van AsperenK. E. P. Van RoozendaalHoogerbrugge NicolineMargriet J. ColleeJ. Margriet ColleeKriege MiekeR. B. Hebon Van Der Luijt EmbraceHebon EmbracePeock SusanFrost DebraSteve D. EllisPlatte RadkaFineberg ElenaD. Gareth EvansLalloo FionaJacobs ChrisEeles RosAdlard JulianDavidson RosemarieDiana EcclesCole TrevorCook JackiePaterson JoanDouglas FionaBrewer CaroleHodgson ShirleyPatrick J. MorrisonWalker LisaMary E. PorteousM. John KennedyPathak HarshAndrew K. Godwin Dominique Stoppa Lyonnet Virginie Caux MoncoutierD. E. Antoine PauwA. De Pauw Marion Gauthier VillarsSylvie MazoyerLeone MelanieCalender AlainLasset ChristineBonadona ValerieHardouin AgnesBerthet Pascaline Yves Jean BignonUhrhammer NancyFaivre LaurenceLoustalot Catherine GemoBuys SaundraDaly Mary BuysS. DalyMiron AlexTerry M. BethMary Beth TerryM. B. TerryWendy K. ChungJohn M. EstherEm JohnSouthey MelissaGoldgar DavidChristian F. Singer Muy Kheng TeaPfeiler Georg Anneliese Fink RetterThomas V. O. HansenTv HansenEjlertsen Bent Oskar Th JohannssonOffit KennethTomas KirchhoffMia M. GaudetVijai JosephRobson MarkPiedmonte Marion Kelly Anne Phillips Linda Van LeJames S. Hoffman Amanda Ewart TolandA. Ewart TolandMontagna MarcoTognazzo SilviaImyanitov EvgenyIsaacs ClaudineC. IssacsJanavicius RamunasLazaro ConxiIgnacio BlancoTornero EvaNavarro MatildeKirsten B. MoysichBeth Y. KarlanGross JennyOlah EdithVaszko Tibor Soo Hwang TeoPatricia A. GanzMary S. BeattieCecelia M. DorflingElizabeth J. Van RensburgDiez OrlandKwong AvaRita K. SchmutzlerWappenschmidt BarbaraEngel ChristophMeindl AlfonsDitsch NinaArnold NorbertHeidemann SimoneNiederacher Dieter Sabine Preisler AdamsGadzicki Dorotehea Raymonda Varon MateevaDeissler HelmutGehrig AndreaSutter ChristianKast KarinFiebig BrittaSchafer DieterCaldes TrinidadMiguel De La HoyaNevanlinna HeliAittomaki KristiinaPlante MarieA. B. Kconfab Spurdle KconfabSusan L. NeuhausenSl Neuhausen Yuan Chun DingWang XianshuLindor NoralaneFredericksen ZacharyV. Shane PankratzPeterlongo PaoloManoukian SiranoushPeissel BernardDaniela ZaffaroniBonanni BernardoBernard LorisRiccardo DolcettiPapi LauraLaura OttiniRadice PaoloMark H. GreenePhuong L. MaiIrene L. AndrulisGlendon GordH. Ocgn Ozcelik OcgnPaul D. P. PharoahPd PharoahSimon A. GaytherJacques SimardDouglas F. EastonFergus J. Couch Georgia Chenevix TrenchO. N. Behalf Of The Consortium Of Investigators Of Modifiers Of Brca1/2

subject

Oncologyendocrine system diseases[SDV]Life Sciences [q-bio]Càncer d'ovariDCN PAC - Perception action and controlCohort StudiesBreast cancer0302 clinical medicinebrca1brca2Odds RatioGenetics (clinical)ComputingMilieux_MISCELLANEOUSOvarian NeoplasmsGenetics0303 health scienceseducation.field_of_studyBRCA1 ProteinHazard ratioMiddle Aged3. Good healthovarian cancer030220 oncology & carcinogenesisFemaleAdultHeterozygotemedicine.medical_specialtyHereditary cancer and cancer-related syndromes Genetics and epigenetic pathways of disease [ONCOL 1]PopulationSingle-nucleotide polymorphismBiologyOvarian Neoplasms - geneticsPolymorphism Single NucleotideArticleCàncer de mama03 medical and health sciencesBreast cancerGermline mutationSDG 3 - Good Health and Well-beingTranslational research [ONCOL 3]Ovarian cancerInternal medicineGeneticsmedicineHumansGenetic Predisposition to Diseaseddc:610Genetics and epigenetic pathways of disease Translational research [NCMLS 6]educationRetrospective Studies030304 developmental biologyBRCA2 ProteinHereditary cancer and cancer-related syndromes [ONCOL 1]associationRetrospective cohort studysnpOdds ratioBRCA1 Protein - geneticsmedicine.diseaseBRCA2 Protein - geneticsMutationOvarian cancerbrca2; snp; brca1; association; ovarian cancer

description

Germline mutations in BRCA1 and BRCA2 are associated with increased risks of breast and ovarian cancer. A genome-wide association study (GWAS) identified six alleles associated with risk of ovarian cancer for women in the general population. We evaluated four of these loci as potential modifiers of ovarian cancer risk for BRCA1 and BRCA2 mutation carriers. Four single-nucleotide polymorphisms (SNPs), rs10088218 (at 8q24), rs2665390 (at 3q25), rs717852 (at 2q31), and rs9303542 (at 17q21), were genotyped in 12,599 BRCA1 and 7,132 BRCA2 carriers, including 2,678 ovarian cancer cases. Associations were evaluated within a retrospective cohort approach. All four loci were associated with ovarian cancer risk in BRCA2 carriers; rs10088218 per-allele hazard ratio (HR) = 0.81 (95% CI: 0.67-0.98) P-trend = 0.033, rs2665390 HR = 1.48 (95% CI: 1.21-1.83) P-trend = 1.8 x 10(-4), rs717852 HR = 1.25 (95% CI: 1.10-1.42) P-trend = 6.6 x 10(-4), rs9303542 HR = 1.16 (95% CI: 1.02-1.33) P-trend = 0.026. Two loci were associated with ovarian cancer risk in BRCA1 carriers; rs10088218 per-allele HR = 0.89 (95% CI: 0.81-0.99) P-trend = 0.029, rs2665390 HR = 1.25 (95% CI: 1.10-1.42) P-trend = 6.1 x 10(-4). The HR estimates for the remaining loci were consistent with odds ratio estimates for the general population. The identification of multiple loci modifying ovarian cancer risk may be useful for counseling women with BRCA1 and BRCA2 mutations regarding their risk of ovarian cancer.

yearjournalcountryeditionlanguage
2012-04-28
https://hdl.handle.net/1887/97590