Hamdi, YosrSoucy, PennyKuchenbaeker, Karoline BPastinen, TomiDroit, ArnaudLemaçon, AudreyAdlard, JulianAittomäki, KristiinaAndrulis, Irene LArason, AdalgeirArnold, NorbertArun, Banu KAzzollini, JacopoBane, AnitaBarjhoux, LaureBarrowdale, DanielBenitez, JavierBerthet, PascalineBlok, Marinus JBobolis, KristieBonadona, ValérieBonanni, BernardoBradbury, Angela RBrewer, CaroleBuecher, BrunoBuys, Saundra SCaligo, Maria AChiquette, JocelyneChung, Wendy KClaes, Kathleen B MDaly, Mary BDamiola, FrancescaDavidson, RosemarieDe la Hoya, MiguelDe Leeneer, KimDiez, OrlandDing, Yuan ChunDolcetti, RiccardoDomchek, Susan MDorfling, Cecilia MEccles, DianaEeles, RosEinbeigi, ZakariaEjlertsen, BentEngel, ChristophGareth Evans, DFeliubadalo, LidiaForetova, LenkaFostira, FlorentiaFoulkes, William DFountzilas, GeorgeFriedman, EitanFrost, DebraGanschow, PamelaGanz, Patricia AGarber, JudyGayther, Simon AGerdes, Anne-MarieGlendon, GordGodwin, Andrew KGoldgar, David EGreene, Mark HGronwald, JacekHahnen, EricHamann, UteHansen, Thomas V OHart, StevenHays, John LHogervorst, Frans B LHulick, Peter JImyanitov, Evgeny NIsaacs, ClaudineIzatt, LouiseJakubowska, AnnaJames, PaulJanavicius, RamunasJensen, Uffe BirkJohn, Esther MJoseph, VijaiJust, WalterKaczmarek, KatarzynaKarlan, Beth YKets, Carolien MKirk, JudyKriege, MiekeLaitman, YaelLaurent, MaïtéLazaro, ConxiLeslie, GoskaLester, JennyLesueur, FabienneLiljegren, AnnelieLoman, NiklasLoud, Jennifer TManoukian, SiranoushMariani, MilenaMazoyer, SylvieMcGuffog, LesleyMeijers-Heijboer, Hanne E JMeindl, AlfonsMiller, AustinMontagna, MarcoMulligan, Anna MarieNathanson, Katherine LNeuhausen, Susan LNevanlinna, HeliNussbaum, Robert LOlah, EdithOlopade, Olufunmilayo IOng, Kai-RenOosterwijk, Jan COsorio, AnaPapi, LauraPark, Sue KyungPedersen, Inge SokildePeissel, BernardSegura, Pedro PerezPeterlongo, PaoloPhelan, Catherine MRadice, PaoloRantala, JohannaRappaport-Fuerhauser, ChristineRennert, GadRichardson, AndreaRobson, MarkRodriguez, Gustavo CRookus, Matti ASchmutzler, Rita KatharinaSevenet, NicolasShah, Payal DSinger, Christian FSlavin, Thomas PSnape, KatieSokolowska, JohannaSønderstrup, Ida Marie HeeholmSouthey, MelissaSpurdle, Amanda BStadler, ZsofiaStoppa-Lyonnet, DominiqueSukiennicki, GrzegorzSutter, ChristianTan, YenTea, Muy-KhengTeixeira, Manuel RTeulé, AlexTeo, Soo-HwangTerry, Mary BethThomassen, MadsTihomirova, LaimaTischkowitz, MarcTognazzo, SilviaToland, Amanda EwartTung, Nadinevan den Ouweland, Ans M Wvan der Luijt, Rob Bvan Engelen, Klaartjevan Rensburg, Elizabeth JVaron-Mateeva, RaymondaWappenschmidt, BarbaraWijnen, Juul TRebbeck, TimothyChenevix-Trench, GeorgiaOffit, KennethCouch, Fergus JNord, SiljeEaston, Douglas FAntoniou, Antonis CSimard, Jacques2019-10-082019-10-082017-01Breast Cancer Res Treat. 2017 Jan;161(1):117-1340167-6806http://hdl.handle.net/20.500.12105/8485PURPOSE: Cis-acting regulatory SNPs resulting in differential allelic expression (DAE) may, in part, explain the underlying phenotypic variation associated with many complex diseases. To investigate whether common variants associated with DAE were involved in breast cancer susceptibility among BRCA1 and BRCA2 mutation carriers, a list of 175 genes was developed based of their involvement in cancer-related pathways. METHODS: Using data from a genome-wide map of SNPs associated with allelic expression, we assessed the association of ~320 SNPs located in the vicinity of these genes with breast and ovarian cancer risks in 15,252 BRCA1 and 8211 BRCA2 mutation carriers ascertained from 54 studies participating in the Consortium of Investigators of Modifiers of BRCA1/2. RESULTS: We identified a region on 11q22.3 that is significantly associated with breast cancer risk in BRCA1 mutation carriers (most significant SNP rs228595 p = 7 × 10-6). This association was absent in BRCA2 carriers (p = 0.57). The 11q22.3 region notably encompasses genes such as ACAT1, NPAT, and ATM. Expression quantitative trait loci associations were observed in both normal breast and tumors across this region, namely for ACAT1, ATM, and other genes. In silico analysis revealed some overlap between top risk-associated SNPs and relevant biological features in mammary cell data, which suggests potential functional significance. CONCLUSION: We identified 11q22.3 as a new modifier locus in BRCA1 carriers. Replication in larger studies using estrogen receptor (ER)-negative or triple-negative (i.e., ER-, progesterone receptor-, and HER2-negative) cases could therefore be helpful to confirm the association of this locus with breast cancer risk.engVoRhttp://creativecommons.org/licenses/by-nc-sa/4.0/BRCA1 and BRCA2 mutation carriersBreast cancerCis-regulatory variantsDifferential allelic expressionGenetic modifiersGenetic susceptibilityBiomarkers, TumorBreast NeoplasmsChromosomes, Human, Pair 11FemaleGene ExpressionGenetic Predisposition to DiseaseGenetic VariationHumansQuantitative Trait LociRiskAllelesGenes, BRCA1Genes, BRCA2HeterozygoteMutationAtribución-NoComercial-CompartirIgual 4.0 Internacional277967161611117-13410.1007/s10549-016-4018-21573-7217Breast cancer research and treatmentopen access