Two truncating variants in FANCC and breast cancer risk.
Thilo DörkPaolo PeterlongoArto MannermaaManjeet K BollaQin WangJoe DennisThomas AhearnIrene L AndrulisHoda Anton-CulverVolker ArndtKristan J AronsonAnnelie AugustinssonLaura E Beane FreemanMatthias W BeckmannAlicia Beeghly-FadielSabine BehrensMarina BermishevaCarl BlomqvistNatalia V BogdanovaStig E BojesenHiltrud B BrauchHermann BrennerBarbara BurwinkelFederico CanzianTsun L ChanJenny Chang-ClaudeStephen J ChanockJi-Yeob ChoiHans ChristiansenChristine L ClarkeFergus J CouchKamila CzeneMary B DalyIsabel Dos-Santos-SilvaMiriam V DwekDiana M EcclesArif Bülent EkiciMikael ErikssonD Gareth EvansPeter Andreas FaschingJonine D FigueroaHenrik FlygerLin FritschiMarike GabrielsonManuela Gago-DominguezChi GaoSusan M GapsturMontserrat García-ClosasJosé A García-SáenzMia M GaudetGraham G GilesMark S GoldbergDavid E GoldgarPascal GuénelLothar HaeberleChristopher A HaimanNiclas HåkanssonPer HallUte HamannMikael HartmanJan HaukeAlexander HeinPeter HillemannsFrans B L HogervorstMaartje J HooningJohn L HopperTony HowellDezheng HuoHidemi ItoMotoki IwasakiAnna JakubowskaWolfgang JanniEsther M JohnAudrey JungRudolf KaaksDaehee KangPooja Middha KapoorElza KhusnutdinovaSung-Won KimCari M KitaharaStella KoutrosPeter KraftVessela N KristensenAva KwongDiether LambrechtsLoic Le MarchandJingmei LiSara LindströmMartha LinetWing-Yee LoJirong LongArtitaya LophatananonJan LubińskiMehdi ManoochehriSiranoush ManoukianSara MargolinElena MartinezKeitaro MatsuoDimitris MavroudisAlfons MeindlUsha MenonJonathan BeesleyNur Aishah Mohd TaibKenneth Ross MuirAnna Marie MulliganSusan L NeuhausenHeli NevanlinnaPatrick NevenWilliam G NewmanKenneth OffitOlufunmilayo I OlopadeAndrew F OlshanJanet E OlsonHåkan OlssonSue K ParkTjoung-Won Park-SimonJulian PetoDijana Plaseska-KaranfilskaEsther Pohl-RescignoNadege PresneauBrigitte RackPaolo RadiceMuhammad U RashidGadi RennertHedy S RennertAtocha RomeroMatthias RuebnerEmmanouil SaloustrosMarjanka K SchmidtRita K SchmutzlerMichael O SchneiderMinouk J SchoemakerChristopher G ScottChen-Yang ShenXiao-Ou ShuJacques SimardSusan SlagerSnezhana SmichkoskaMelissa C SoutheyJohn J SpinelliJennifer StoneHarald SurowyAnthony J SwerdlowRulla M TamimiWilliam J TapperSoo H TeoMary Beth TerryAmanda E TolandRob A E M TollenaarDiana TorresGabriela Torres-MejíaMelissa A TroesterThérèse TruongShoichiro TsuganeMichael UntchCeline M VachonAns M W van den OuwelandElke M van VeenJoseph VijaiCamilla WendtAlicja WolkJyh-Cherng YuWei ZhengArgyrios ZiogasElad Zivnull nullnull nullAlison M DunningPaul David Peter PharoahDetlev SchindlerPeter DevileeDouglas F EastonPublished in: Scientific reports (2019)
Fanconi anemia (FA) is a genetically heterogeneous disorder with 22 disease-causing genes reported to date. In some FA genes, monoallelic mutations have been found to be associated with breast cancer risk, while the risk associations of others remain unknown. The gene for FA type C, FANCC, has been proposed as a breast cancer susceptibility gene based on epidemiological and sequencing studies. We used the Oncoarray project to genotype two truncating FANCC variants (p.R185X and p.R548X) in 64,760 breast cancer cases and 49,793 controls of European descent. FANCC mutations were observed in 25 cases (14 with p.R185X, 11 with p.R548X) and 26 controls (18 with p.R185X, 8 with p.R548X). There was no evidence of an association with the risk of breast cancer, neither overall (odds ratio 0.77, 95%CI 0.44-1.33, p = 0.4) nor by histology, hormone receptor status, age or family history. We conclude that the breast cancer risk association of these two FANCC variants, if any, is much smaller than for BRCA1, BRCA2 or PALB2 mutations. If this applies to all truncating variants in FANCC it would suggest there are differences between FA genes in their roles on breast cancer risk and demonstrates the merit of large consortia for clarifying risk associations of rare variants.