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dc.contributor.authorGhoussaini, Men_US
dc.contributor.authorFrench, JDen_US
dc.contributor.authorMichailidou, Ken_US
dc.contributor.authorNord, Sen_US
dc.contributor.authorBeesley, Jen_US
dc.contributor.authorCanisus, Sen_US
dc.contributor.authorHillman, KMen_US
dc.contributor.authorKaufmann, Sen_US
dc.contributor.authorSivakumaran, Hen_US
dc.contributor.authorMoradi Marjaneh, Men_US
dc.contributor.authorLee, JSen_US
dc.contributor.authorDennis, Jen_US
dc.contributor.authorBolla, MKen_US
dc.contributor.authorWang, Qen_US
dc.contributor.authorDicks, Een_US
dc.contributor.authorMilne, RLen_US
dc.contributor.authorHopper, JLen_US
dc.contributor.authorSouthey, MCen_US
dc.contributor.authorSchmidt, MKen_US
dc.contributor.authorBroeks, Aen_US
dc.contributor.authorMuir, Ken_US
dc.contributor.authorLophatananon, Aen_US
dc.contributor.authorFasching, PAen_US
dc.contributor.authorBeckmann, MWen_US
dc.contributor.authorFletcher, Oen_US
dc.contributor.authorJohnson, Nen_US
dc.contributor.authorSawyer, EJen_US
dc.contributor.authorTomlinson, Ien_US
dc.contributor.authorBurwinkel, Ben_US
dc.contributor.authorMarme, Fen_US
dc.contributor.authorGuénel, Pen_US
dc.contributor.authorTruong, Ten_US
dc.contributor.authorBojesen, SEen_US
dc.contributor.authorFlyger, Hen_US
dc.contributor.authorBenitez, Jen_US
dc.contributor.authorGonzález-Neira, Aen_US
dc.contributor.authorAlonso, MRen_US
dc.contributor.authorPita, Gen_US
dc.contributor.authorNeuhausen, SLen_US
dc.contributor.authorAnton-Culver, Hen_US
dc.contributor.authorBrenner, Hen_US
dc.contributor.authorArndt, Ven_US
dc.contributor.authorMeindl, Aen_US
dc.contributor.authorSchmutzler, RKen_US
dc.contributor.authorBrauch, Hen_US
dc.contributor.authorHamann, Uen_US
dc.contributor.authorTessier, DCen_US
dc.contributor.authorVincent, Den_US
dc.contributor.authorNevanlinna, Hen_US
dc.contributor.authorKhan, Sen_US
dc.contributor.authorMatsuo, Ken_US
dc.contributor.authorIto, Hen_US
dc.contributor.authorDörk, Ten_US
dc.contributor.authorBogdanova, NVen_US
dc.contributor.authorLindblom, Aen_US
dc.contributor.authorMargolin, Sen_US
dc.contributor.authorMannermaa, Aen_US
dc.contributor.authorKosma, VMen_US
dc.contributor.authorWu, AHen_US
dc.contributor.authorVan Den Berg, Den_US
dc.contributor.authorLambrechts, Den_US
dc.contributor.authorFloris, Gen_US
dc.contributor.authorChang-Claude, Jen_US
dc.contributor.authorRudolph, Aen_US
dc.contributor.authorRadice, Pen_US
dc.contributor.authorBarile, Men_US
dc.contributor.authorCouch, FJen_US
dc.contributor.authorHallberg, Een_US
dc.contributor.authorGiles, GGen_US
dc.contributor.authorHaiman, CAen_US
dc.contributor.authorLe Marchand, Len_US
dc.contributor.authorGoldberg, MSen_US
dc.contributor.authorTeo, SHen_US
dc.contributor.authorYip, CHen_US
dc.contributor.authorBorresen-Dale, ALen_US
dc.contributor.authorZheng, Wen_US
dc.contributor.authorCai, Qen_US
dc.contributor.authorWinqvist, Ren_US
dc.contributor.authorPylkäs, Ken_US
dc.contributor.authorAndrulis, ILen_US
dc.contributor.authorDevilee, Pen_US
dc.contributor.authorTollenaar, RAen_US
dc.contributor.authorGarcía-Closas, Men_US
dc.contributor.authorFigueroa, Jen_US
dc.contributor.authorHall, Pen_US
dc.contributor.authorCzene, Ken_US
dc.contributor.authorBrand, JSen_US
dc.contributor.authorDarabi, Hen_US
dc.contributor.authorEriksson, Men_US
dc.contributor.authorHooning, MJen_US
dc.contributor.authorKoppert, LBen_US
dc.contributor.authorLi, Jen_US
dc.contributor.authorShu, XOen_US
dc.contributor.authorZheng, Yen_US
dc.contributor.authorCox, Aen_US
dc.contributor.authorCross, SSen_US
dc.contributor.authorShah, Men_US
dc.contributor.authorRhenius, Ven_US
dc.contributor.authorChoi, JYen_US
dc.contributor.authorKang, Den_US
dc.contributor.authorHartman, Men_US
dc.contributor.authorChia, KSen_US
dc.contributor.authorKabisch, Men_US
dc.contributor.authorTorres, Den_US
dc.contributor.authorLuccarini, Cen_US
dc.contributor.authorConroy, DMen_US
dc.contributor.authorJakubowska, Aen_US
dc.contributor.authorLubinski, Jen_US
dc.contributor.authorSangrajrang, Sen_US
dc.contributor.authorBrennan, Pen_US
dc.contributor.authorOlswold, Cen_US
dc.contributor.authorSlager, Sen_US
dc.contributor.authorShen, CYen_US
dc.contributor.authorHou, MFen_US
dc.contributor.authorSwerdlow, Aen_US
dc.contributor.authorSchoemaker, MJen_US
dc.contributor.authorSimard, Jen_US
dc.contributor.authorPharoah, PDen_US
dc.contributor.authorKristensen, Ven_US
dc.contributor.authorChenevix-Trench, Gen_US
dc.contributor.authorEaston, DFen_US
dc.contributor.authorDunning, AMen_US
dc.contributor.authorEdwards, SLen_US
dc.date.accessioned2016-09-28T12:12:57Z
dc.date.issued2016-09-03en_US
dc.identifier.citationAmerican journal of human genetics, 2016en_US
dc.identifier.issn0002-9297en_US
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/140
dc.identifier.eissn1537-6605en_US
dc.identifier.doi10.1016/j.ajhg.2016.07.017en_US
dc.description.abstractGenome-wide association studies (GWASs) have revealed increased breast cancer risk associated with multiple genetic variants at 5p12. Here, we report the fine mapping of this locus using data from 104,660 subjects from 50 case-control studies in the Breast Cancer Association Consortium (BCAC). With data for 3,365 genotyped and imputed SNPs across a 1 Mb region (positions 44,394,495-45,364,167; NCBI build 37), we found evidence for at least three independent signals: the strongest signal, consisting of a single SNP rs10941679, was associated with risk of estrogen receptor-positive (ER(+)) breast cancer (per-g allele OR ER(+) = 1.15; 95% CI 1.13-1.18; p = 8.35 × 10(-30)). After adjustment for rs10941679, we detected signal 2, consisting of 38 SNPs more strongly associated with ER-negative (ER(-)) breast cancer (lead SNP rs6864776: per-a allele OR ER(-) = 1.10; 95% CI 1.05-1.14; p conditional = 1.44 × 10(-12)), and a single signal 3 SNP (rs200229088: per-t allele OR ER(+) = 1.12; 95% CI 1.09-1.15; p conditional = 1.12 × 10(-05)). Expression quantitative trait locus analysis in normal breast tissues and breast tumors showed that the g (risk) allele of rs10941679 was associated with increased expression of FGF10 and MRPS30. Functional assays demonstrated that SNP rs10941679 maps to an enhancer element that physically interacts with the FGF10 and MRPS30 promoter regions in breast cancer cell lines. FGF10 is an oncogene that binds to FGFR2 and is overexpressed in ∼10% of human breast cancers, whereas MRPS30 plays a key role in apoptosis. These data suggest that the strongest signal of association at 5p12 is mediated through coordinated activation of FGF10 and MRPS30, two candidate genes for breast cancer pathogenesis.en_US
dc.formatPrint-Electronicen_US
dc.languageengen_US
dc.language.isoengen_US
dc.subjectkConFab/AOCS Investigatorsen_US
dc.subjectNBCS Collaboratorsen_US
dc.titleEvidence that the 5p12 Variant rs10941679 Confers Susceptibility to Estrogen Receptor-Positive Breast Cancer through FGF10 and MRPS30 Regulation.en_US
dc.typeJournal Article
dcterms.dateAccepted2016-07-16en_US
rioxxterms.versionofrecord10.1016/j.ajhg.2016.07.017en_US
rioxxterms.licenseref.startdate2016-09-03en_US
rioxxterms.typeJournal Article/Reviewen_US
dc.relation.isPartOfAmerican journal of human geneticsen_US
pubs.notesNot knownen_US
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research/Aetiological Epidemiology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research/Functional Genetic Epidemiology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Genetics and Epidemiology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Genetics and Epidemiology/Aetiological Epidemiology
pubs.embargo.termsNot knownen_US
icr.researchteamFunctional Genetic Epidemiologyen_US
icr.researchteamAetiological Epidemiologyen_US
dc.contributor.icrauthorSwerdlow, Anthonyen_US
dc.contributor.icrauthorSchoemaker, Minouken_US
dc.contributor.icrauthorFletcher, Oliviaen_US


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