biostudies-literatureBojesen SECancer Research UKBreast Cancer NowNational Institute for Health Research (NIHR)NCI NIH HHSCancer Foundation Finland srWellcome TrustCIHR371-84, 384e1-2https://www.ebi.ac.uk/biostudies/studies/S-EPMC3670748biostudies-literatureUnknown45(4)TERT-locus SNPs and leukocyte telomere measures are reportedly associated with risks of multiple cancers. Using the Illumina custom genotyping array iCOGs, we analyzed ∼480 SNPs at the TERT locus in breast (n = 103,991), ovarian (n = 39,774) and BRCA1 mutation carrier (n = 11,705) cancer cases and controls. Leukocyte telomere measurements were also available for 53,724 participants. Most associations cluster into three independent peaks. The minor allele at the peak 1 SNP rs2736108 associates with longer telomeres (P = 5.8 × 10(-7)), lower risks for estrogen receptor (ER)-negative (P = 1.0 × 10(-8)) and BRCA1 mutation carrier (P = 1.1 × 10(-5)) breast cancers and altered promoter assay signal. The minor allele at the peak 2 SNP rs7705526 associates with longer telomeres (P = 2.3 × 10(-14))Nature geneticsMultiple independent variants at the TERT locus are associated with telomere length and risks of breast and ovarian cancer.PMC367074815960P30 CA00874813086C1287/A10118C12292/A11174C1287/A10710R01 CA149429R01 CA128978C1287/A9540P30 CA07178909053210118P30 CA016520R01 CA12244303/DHCS/03/G121/5111022P30 CA076292R01 CA112523165611656511013511174P30 CA072720076113P50 CA116201R37 CA070867BREAST CANCER NOW RESEARCH CENTREC1287/A12014RC4 CA153828R01 CA092447P50 CA136393R01 CA087538CA116201U19 CA148112CA12897810124R01 CA083918Flanagan JMPankratz VSSouthey MCPeock SNathanson KLWoods NMelin BSieh WLabreche FFletcher OWalker LShen CYBacot FMai PLKelemen LEPerez JISchmutzler RKFigueroa JHealey SCaron OHosono SMiller NKarlan BYRudolph AKruse TASzabo CIFaivre LFrench JDTyrer JPVierkant RADolcetti RBojesen SEBogdanova NVDumont MLuben RLambrechts SPeterlongo PTessier DCHogervorst FBLindblom APooley KANarod SALambrechts DWu AHAltena AMden Ouweland AMVincent DSiddiqui NPaul JAntoniou ACFineberg ENordestgaard BGMenkiszak JEvans DGBonadona VSimard JChen XKauppila SSellers TAStewart-Brown SYip CHKiemeney LAHartikainen JMMassuger LFTeo SHTajima KSchmidt MKEccles DNevanlinna HKennedy MJEllis SDMuller HKjaer SKLiu JMarme FGiraud SSwerdlow ADoherty JAPylkas Kvan der Luijt RBEdwards SLDeming-Halverson SDespierre EArnold NRadice PSoller MBidzinski MIau PTYoo KYBlanco IOlswold CDurst Mvan den Berg DMcGuire VDennis JIwata HSawyer EJOlson JEBarile MFicarazzi FWappenschmidt BJakubowska AHartman MMannermaa ASlager SBruning TPaluch SSHeitz FShah MDork TSalani RAhmed SFountzilas GAzmi MALubinski JVachon CRobson MKerin MJDicks EBlomqvist CGentry-Maharaj ASalvesen HBZaffaroni DBalasubramanian SPJukkola-Vuorinen AHumphreys KPeto JPeissel BKonecny GEBrenner HNeuhausen SLPermuth-Wey JKataja VJaworska KSignorello LBKristensen VBenitez JDansonka-Mieszkowska ACole TNiederacher DMulot CRookus MAGenetic Modifiers of Cancer Risk in BRCA1/2 Mutation Carriers (GEMO)Knight JAWik ECox AYang HPWang-Gohrke SWeitzel JNWilkens LRVitonis AFNess RBMontagna MHogdall EWentzensen NRisch HABuecher BDitsch NYu JCDurda KLophatananon AJensen UBAustralian Ovarian Cancer StudySchumacher FGiannini GBraaf LMWoo YLAittomaki KOosterwijk JCSangrajrang SChang-Claude JJohnatty SEDavidson RTseng CCNickels SMulligan AMKupryjanczyk JRantala JPlatte RPiedmonte MMazoyer SSilva Idos SLe NDBressac-de Paillerets BCaux-Moncoutier VPoole EMAnton-Culver HBandera EVMiao HOlson SHShridhar VKathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer (kConFab)Gore MAshworth ADevilee PTsimiklis HBrouwers BOrlow IPlendl HCzene KMargolin SHereditary Breast and Ovarian Cancer Research Group Netherlands (HEBON)Mensenkamp ARShu XOGene Environment Interaction and Breast Cancer (GENICA)Cicek MSZamora MPTeoman ABorg AHamann UFridley BLCaldes TFlesch-Janys DEjlertsen BBernard LFrost DBaglietto LLe Marchand LMcGuffog LBurwinkel BHoatlin MEaston DFMuranen TAWauters ETollenaar RAShapiro CHein RSinilnikova OMHooning MJLester JHall PHealey CSReddel RRSmart CEGreene MHBeesley JGhoussaini MIversen EGibson LLush MRzepecka IKGayther SAMonteiro ANLuccarini CWinterhoff BKalli KRBarrowdale DPhelan CMMaranian MJvan Asperen CJBarwell JAntonenkova NNSpurdle ABPita GManoukian SHenderson BEWhittemore ASKuchenbaecker KBRossing MAGarcia-Closas MCollee JMBlot WKriege MWeber RPOs TALaurent-Puig PSeynaeve COffit KGuenel PPickett HAJager APike MCHarter PSinger CFSwedish Breast Cancer Study (SWE-BRCA)Chenevix-Trench GChanock SJLaitman YMilne RLLi JFasching PASutter CJones MSoucy PMichailidou Kvan der Schoot CERodriguez GCBerchuck ACai QGlendon GTeh YCCook LSRodriguez-Rodriguez LPejovic TCai HJensen AHollestelle AMenon UYannoukakos DFrenay MSavage SAGao YTAustralian Cancer StudyMuir KToloczko-Grabarek ATea MKHaiman CAGodwin AKArun BKSkytte ABJohnston RLMcLaughlin JRByrski TAlvarez NEngelholm SAOlah EMoysich KBHartmann ASchoof NGerdes AMStoppa-Lyonnet DLissowska JGoode ELFlyger HHansen TVBaynes CRhiem KHogdall CKGoldgar DETihomirova LRogmann LApicella CDeissler HLarson MCGronwald JOdunsi KShrubsole MEdwards RDomchek SMIkram MKEkici ABZheng WLux MPYatabe YHillemanns PTworoger SSWinqvist RTruong TPearce CLHsiung CNEpidemiological study of BRCA1 & BRCA2 Mutation Carriers (EMBRACE)Brauch HSeveri GWildiers HMcKay JLevine DAStutz MDLee AEngel CGaborieau VBonanni BRebbeck TRSchildkraut JMZiogas APelttari LMKaulich DGGoodman MTBroeks ALakhani SRKo YDImyanitov ENDunning AMvan Roozendaal KEdu Bois ACybulski CWeischer MKosma VMMartens JWLu WAndrulis ILGoldberg MSLu YNakanishi TMatsuo KMeijers-Heijboer HGarber JPharoah PDThomassen MWang QKang DIto HCouch FJWang XTeo YYSiriwanarangsan PBunker CHBolla MKYang GShen HCStegmaier CSchwaab INielsen SFFriedman EOrr NCarney MEArndt VLeminen ABrooks-Wilson ALong JTerry KLGarcia JJSohn CNoh DYTomlinson IKrakstad CForetova LLurie GGiles GGBeckmann MWRamus SJCunningham JMSchneeweiss AGonzalez-Neira ACramer DWLawrenson KHou MFKarevan RAben KKVergote IHillman KMStram DOSong HArmasu SMHalle MKOmar SZCampbell ILichtner PHopper JLDamiola FButzow RBrown JRunnebaum IAdemuyiwa FMeindl ABrown RfalseMultiple independent variants at the TERT locus are associated with telomere length and risks of breast and ovarian cancer.TERT-locus SNPs and leukocyte telomere measures are reportedly associated with risks of multiple cancers. Using the Illumina custom genotyping array iCOGs, we analyzed ∼480 SNPs at the TERT locus in breast (n = 103,991), ovarian (n = 39,774) and BRCA1 mutation carrier (n = 11,705) cancer cases and controls. Leukocyte telomere measurements were also available for 53,724 participants. Most associations cluster into three independent peaks. The minor allele at the peak 1 SNP rs2736108 associates with longer telomeres (P = 5.8 × 10(-7)), lower risks for estrogen receptor (ER)-negative (P = 1.0 × 10(-8)) and BRCA1 mutation carrier (P = 1.1 × 10(-5)) breast cancers and altered promoter assay signal. The minor allele at the peak 2 SNP rs7705526 associates with longer telomeres (P = 2.3 × 10(-14))2013-01-01T00:00:00Z2013 Apr2026-05-01T04:59:53.769Z2026-04-07T16:40:43.114ZS-EPMC36707482353573110.1038/ng.2566