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dc.contributor.authorCheng, Timothy HTen
dc.contributor.authorThompson, Deborahen
dc.contributor.authorO’Mara, Tracy Aen
dc.contributor.authorPainter, Jodie Nen
dc.contributor.authorGlubb, Dylan Men
dc.contributor.authorFlach, Susanneen
dc.contributor.authorLewis, Annabelleen
dc.contributor.authorFrench, Juliet Den
dc.contributor.authorFreeman-Mills, Lukeen
dc.contributor.authorChurch, Daviden
dc.contributor.authorGorman, Maggieen
dc.contributor.authorMartin, Lynnen
dc.contributor.authorNational, Study of Endometrial Cancer Genetics Group NSECGen
dc.contributor.authorHodgson, Shirleyen
dc.contributor.authorWebb, Penelope Men
dc.contributor.authorThe, Australian National Endometrial Cancer Study Group ANECSen
dc.contributor.authorAttia, Johnen
dc.contributor.authorHolliday, Elizabeth Gen
dc.contributor.authorMcEvoy, Marken
dc.contributor.authorScott, Rodney Jen
dc.contributor.authorHenders, Anjali Ken
dc.contributor.authorMartin, Nicholas Gen
dc.contributor.authorMontgomery, Grant Wen
dc.contributor.authorNyholt, Dale Ren
dc.contributor.authorAhmed, Shahanaen
dc.contributor.authorHealey, Catherine Sen
dc.contributor.authorShah, Mitulen
dc.contributor.authorDennis, Joeen
dc.contributor.authorFasching, Peter Aen
dc.contributor.authorBeckmann, Matthias Wen
dc.contributor.authorHein, Alexanderen
dc.contributor.authorEkici, Arif Ben
dc.contributor.authorHall, Peren
dc.contributor.authorCzene, Kamilaen
dc.contributor.authorDarabi, Hatefen
dc.contributor.authorLi, Jingmeien
dc.contributor.authorDörk, Thiloen
dc.contributor.authorDürst, Matthiasen
dc.contributor.authorHillemanns, Peteren
dc.contributor.authorRunnebaum, Ingoen
dc.contributor.authorAmant, Fredericen
dc.contributor.authorSchrauwen, Stefanieen
dc.contributor.authorZhao, Huien
dc.contributor.authorLambrechts, Dietheren
dc.contributor.authorJeroen, Depreeuwen
dc.contributor.authorDowdy, Sean Cen
dc.contributor.authorGoode, Ellen Len
dc.contributor.authorFridley, Brooke Len
dc.contributor.authorWinham, Stacey Jen
dc.contributor.authorNjølstad, Tormund Sen
dc.contributor.authorSalvesen, Helga Ben
dc.contributor.authorTrovik, Joneen
dc.contributor.authorWerner, Henrica MJen
dc.contributor.authorAshton, Katieen
dc.contributor.authorOtton, Geoffreyen
dc.contributor.authorProietto, Tonyen
dc.contributor.authorLiu, Taoen
dc.contributor.authorMints, Miriamen
dc.contributor.authorTham, Emmaen
dc.contributor.authorRENDOCAS,en
dc.contributor.authorCHIBCHA, Consortiumen
dc.contributor.authorLi, Mulin Junen
dc.contributor.authorYip, Shun Hen
dc.contributor.authorWang, Junwenen
dc.contributor.authorBolla, Manjeet Ken
dc.contributor.authorMichailidou, Kyriakien
dc.contributor.authorWang, Jeanen
dc.contributor.authorTyrer, Jonathanen
dc.contributor.authorDunlop, Malcolmen
dc.contributor.authorHoulston, Richarden
dc.contributor.authorPalles, Claireen
dc.contributor.authorHopper, John Len
dc.contributor.authorAOCS, Groupen
dc.contributor.authorPeto, Julianen
dc.contributor.authorSwerdlow, Anthony Jen
dc.contributor.authorBurwinkel, Barbaraen
dc.contributor.authorHermann, Brenneren
dc.contributor.authorMeindl, Alfonsen
dc.contributor.authorBrauch, Hiltruden
dc.contributor.authorLindblom, Annikaen
dc.contributor.authorChang-Claude, Jennyen
dc.contributor.authorCouch, Fergus Jen
dc.contributor.authorGiles, Graham Gen
dc.contributor.authorKristensen, Vessela Nen
dc.contributor.authorCox, Angelaen
dc.contributor.authorCunningham, Julie Men
dc.contributor.authorPharoah, Paulen
dc.contributor.authorDunning, Alisonen
dc.contributor.authorEdwards, Stacey Len
dc.contributor.authorEaston, Douglasen
dc.contributor.authorTomlinson, Ianen
dc.contributor.authorSpurdle, Amanda Ben
dc.date.accessioned2016-05-18T15:18:27Z
dc.date.available2016-05-18T15:18:27Z
dc.date.issued2016-05-02en
dc.identifier.citationCheng et al. Nature Genetics (2016). doi: 10.1038/ng.3562en
dc.identifier.issn1061-4036
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/256057
dc.description.abstractWe conducted a meta-analysis of three endometrial cancer genome-wide association studies (GWAS) and two follow-up phases totaling 7,737 endometrial cancer cases and 37,144 controls of European ancestry. Genome-wide imputation and meta-analysis identified five new risk loci of genome-wide significance at likely regulatory regions on chromosomes 13q22.1 (rs11841589, near KLF5), 6q22.31 (rs13328298, in LOC643623 and near HEY2 and NCOA7), 8q24.21 (rs4733613, telomeric to MYC), 15q15.1 (rs937213, in EIF2AK4, near BMF) and 14q32.33 (rs2498796, in AKT1, near SIVA1). We also found a second independent 8q24.21 signal (rs17232730). Functional studies of the 13q22.1 locus showed that rs9600103 (pairwise r2 = 0.98 with rs11841589) is located in a region of active chromatin that interacts with the KLF5 promoter region. The rs9600103[T] allele that is protective in endometrial cancer suppressed gene expression in vitro, suggesting that regulation of the expression of KLF5, a gene linked to uterine development, is implicated in tumorigenesis. These findings provide enhanced insight into the genetic and biological basis of endometrial cancer.
dc.description.sponsorshipI.T. is supported by Cancer Research UK and the Oxford Comprehensive Biomedical Research Centre. T.H.T.C. is supported by the Rhodes Trust and the Nuffield Department of Medicine. Funding for iCOGS infrastructure came from the European Community's Seventh Framework Programme under grant agreement 223175 (HEALTH-F2-2009-223175) (COGS), Cancer Research UK (C1287/A10118, C1287/A10710, C12292/A11174, C1281/A12014, C5047/A8384, C5047/A15007, C5047/A10692 and C8197/A16565), the US National Institutes of Health (R01 CA128978, U19 CA148537, U19 CA148065 and U19 CA148112), the US Department of Defense (W81XWH-10-1-0341), the Canadian Institutes of Health Research (CIHR) for the CIHR Team in Familial Risks of Breast Cancer, the Susan G. Komen Foundation for the Cure, the Breast Cancer Research Foundation and the Ovarian Cancer Research Fund. SEARCH recruitment was funded by a programme grant from Cancer Research UK (C490/A10124). Stage 1 and stage 2 case genotyping was supported by the NHMRC (552402 and 1031333). Control data were generated by the WTCCC, and a full list of the investigators who contributed to the generation of the data is available from the WTCCC website. We acknowledge use of DNA from the British 1958 Birth Cohort collection, funded by UK Medical Research Council grant G0000934 and Wellcome Trust grant 068545/Z/02; funding for this project was provided by the Wellcome Trust under award 085475. NSECG was supported by the European Union's Framework Programme 7 CHIBCHA grant and Wellcome Trust Centre for Human Genetics Core Grant 090532/Z/09Z, and CORGI was funded by Cancer Research UK. BCAC is funded by Cancer Research UK (C1287/A10118 and C1287/A12014). OCAC is supported by a grant from the Ovarian Cancer Research Fund thanks to donations by the family and friends of Kathryn Sladek Smith (PPD/RPCI.07) and the UK National Institute for Health Research Biomedical Research Centres at the University of Cambridge.
dc.languageEnglishen
dc.language.isoenen
dc.publisherNature Publishing Group
dc.subjectendometrial canceren
dc.subjectgenome-wide association studiesen
dc.subjectgynaecological canceren
dc.titleFive endometrial cancer risk loci identified through genome-wide association analysisen
dc.typeArticle
dc.description.versionThis is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/ng.3562en
prism.publicationDate2016en
prism.publicationNameNature Geneticsen
dc.rioxxterms.funderCRUK
dc.rioxxterms.funderMRC
dc.rioxxterms.funderWellcome Trust
dcterms.dateAccepted2016-04-08en
rioxxterms.versionofrecord10.1038/ng.3562en
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2016-05-02en
dc.contributor.orcidThompson, Deborah [0000-0003-1465-5799]
dc.contributor.orcidDennis, Joe [0000-0003-4591-1214]
dc.contributor.orcidWang, Jean [0000-0002-9139-0627]
dc.contributor.orcidTyrer, Jonathan [0000-0003-3724-4757]
dc.contributor.orcidPharoah, Paul [0000-0001-8494-732X]
dc.contributor.orcidDunning, Alison [0000-0001-6651-7166]
dc.contributor.orcidEaston, Douglas [0000-0003-2444-3247]
dc.identifier.eissn1546-1718
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idCancer Research UK (10119)
pubs.funder-project-idCancer Research UK (10124)
pubs.funder-project-idCancer Research UK (A11020)
pubs.funder-project-idCancer Research UK (11021)
pubs.funder-project-idCancer Research UK (16561)
pubs.funder-project-idNational Cancer Institute (NCI) (R01CA128978)
pubs.funder-project-idNational Cancer Institute (NCI) (U19CA148537)
pubs.funder-project-idNational Cancer Institute (NCI) (U19CA148065)
pubs.funder-project-idEC FP7 CP (223175)
pubs.funder-project-idCancer Research UK (CRUK-A10710)
pubs.funder-project-idCancer Research UK (CRUK-A12014)
pubs.funder-project-idCancer Research UK (CRUK-A10118)
pubs.funder-project-idNational Health and Medical Research Council (1031333)
rioxxterms.freetoread.startdate2016-11-02


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