biostudies-literaturePeterlongo PSpanish Health Research FoundationCanada Research Chairs SecretariatSpanish Carlos III Health InstituteSpanish Network on Rare DiseasesNational Institutes of HealthBerta Kamprad FoundationAssociazione Italiana per la Ricerca sul CancroGunnar Nilsson FoundationAsociación Española Contra el CáncerUNICANCERSwedish Society of MedicineLigue Nationale Contre le CancerICREA Academia, Generalitat de CatalunyaNSERCNatural Sciences and Engineering Research Council of CanadaMinistero della Salute, ItalyRamón Areces FoundationNIHCanadian Foundation for InnovationCRO Aviano National Cancer InstituteCanadian Breast Cancer FoundationMINECOFrench National Institute of CancerBreast Cancer Research FoundationCatalan Health Institute and Autonomous Government of CataloniaSwedish Cancer SocietyNCI NIH HHSBioCAREIstituto Oncologico Veneto IOV – IRCCSFondazione IRCCS Istituto Nazionale Tumori5345-55https://www.ebi.ac.uk/biostudies/studies/S-EPMC4550823biostudies-literatureUnknown24(18)Numerous genetic factors that influence breast cancer risk are known. However, approximately two-thirds of the overall familial risk remain unexplained. To determine whether some of the missing heritability is due to rare variants conferring high to moderate risk, we tested for an association between the c.5791C>T nonsense mutation (p.Arg1931*; rs144567652) in exon 22 of FANCM gene and breast cancer. An analysis of genotyping data from 8635 familial breast cancer cases and 6625 controls from different countries yielded an association between the c.5791C>T mutation and breast cancer risk [odds ratio (OR) = 3.93 (95% confidence interval (CI) = 1.28-12.11; P = 0.017)]. Moreover, we performed two meta-analyses of studies from countries with carriers in both cases and controls and of all availaHuman molecular geneticsFANCM c.5791C>T nonsense mutation (rs144567652) induces exon skipping, affects DNA repair activity and is a familial breast cancer risk factor.PMC4550823IG 5706U01 CA116167CA176785SGR0489-2009, SGR317-2014P30 CA008748PI13/00285R01 CA176785ISCIIIRETIC RD12/0036/0082009SGR290AIRC-IG 12821PI12/02585R01 CA1289782009SGR283SAF2012-31881PI12/01528R01 CA116167PI10/01422CA116167IG 12780371758-2009CA128978Bernard LCatucci IVolorio SSWE-BRCACortesi LMencarelli MABurwinkel BRizzolo PBaldassarri MTibiletti MGSpina FPierotti MAEhrencrona HRogan PKSilvestri VSinilnikova OMPeissel BSchmutzler RKCaleca LVerderio PColombo MVijai JMucaki EKvist ALazaro CSornin VRenieri ADolcetti RBenitez JCaligo MABonanni BCorna CSurowy Hvan Asperen CJPeterlongo PBartram CGambino GHauke JMarchi IMarin MBalestrino LHilbers FSManoukian SMontagna MEon-Marchais SBogliolo MPapi LJames PAMitchell GBalmana JAgata SPutignano ALTartari CCapone GLGENESISOffit KThompson EPilato BCouch FJWang XAndrieu NRoversi GPerfumo CPizzamiglio SSutter CkConFabFederico MDella Puppa LTondini CMazoyer SFalanga ADall'Olio VVivanet CVaresco LVerzeroli CPensotti VDiez ODondon MGMarchetti MRadice PViassolo VMatricardi LDevilee POttini LTognazzo STommasi SPujana MAOsorio ACini GSurralles JViel ABarile MCampbell IDamiola FMedici VGismondi VStoppa-Lyonnet DGenuardi MMeindl AfalseFANCM c.5791C>T nonsense mutation (rs144567652) induces exon skipping, affects DNA repair activity and is a familial breast cancer risk factor.Numerous genetic factors that influence breast cancer risk are known. However, approximately two-thirds of the overall familial risk remain unexplained. To determine whether some of the missing heritability is due to rare variants conferring high to moderate risk, we tested for an association between the c.5791C>T nonsense mutation (p.Arg1931*; rs144567652) in exon 22 of FANCM gene and breast cancer. An analysis of genotyping data from 8635 familial breast cancer cases and 6625 controls from different countries yielded an association between the c.5791C>T mutation and breast cancer risk [odds ratio (OR) = 3.93 (95% confidence interval (CI) = 1.28-12.11; P = 0.017)]. Moreover, we performed two meta-analyses of studies from countries with carriers in both cases and controls and of all availa2015-01-01T00:00:00Z2015 Sep2026-05-30T11:18:05.847Z2019-03-27T01:57:23ZS-EPMC45508232613069510.1093/hmg/ddv251