Five endometrial cancer risk loci identified through genome-wide association analysis.

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dc.creatorCheng, Timothy Ht
dc.creatorThompson, Deborah J
dc.creatorO'Mara, Tracy A
dc.creatorPainter, Jodie N
dc.creatorGlubb, Dylan M
dc.creatorFlach, Susanne
dc.creatorLewis, Annabelle
dc.creatorFrench, Juliet D
dc.creatorFreeman-Mills, Luke
dc.creatorChurch, David
dc.creatorGorman, Maggie
dc.creatorMartin, Lynn
dc.creatorNational Study of Endometrial Cancer Genetics Group (NSECG)
dc.creatorHodgson, Shirley
dc.creatorWebb, Penelope M
dc.creatorAustralian National Endometrial Cancer Study Group (ANECS)
dc.creatorAttia, John
dc.creatorHolliday, Elizabeth G
dc.creatorMcEvoy, Mark
dc.creatorScott, Rodney J
dc.creatorHenders, Anjali K
dc.creatorMartin, Nicholas G
dc.creatorMontgomery, Grant W
dc.creatorNyholt, Dale R
dc.creatorAhmed, Shahana
dc.creatorHealey, Catherine S
dc.creatorShah, Mitul
dc.creatorDennis, Joe
dc.creatorFasching, Peter A
dc.creatorBeckmann, Matthias W
dc.creatorHein, Alexander
dc.creatorEkici, Arif B
dc.creatorHall, Per
dc.creatorCzene, Kamila
dc.creatorDarabi, Hatef
dc.creatorLi, Jingmei
dc.creatorDörk, Thilo
dc.creatorDürst, Matthias
dc.creatorHillemanns, Peter
dc.creatorRunnebaum, Ingo
dc.creatorAmant, Frederic
dc.creatorSchrauwen, Stefanie
dc.creatorZhao, Hui
dc.creatorLambrechts, Diether
dc.creatorDepreeuw, Jeroen
dc.creatorDowdy, Sean C
dc.creatorGoode, Ellen L
dc.creatorFridley, Brooke L
dc.creatorWinham, Stacey J
dc.creatorNjølstad, Tormund S
dc.creatorSalvesen, Helga B
dc.creatorTrovik, Jone
dc.creatorWerner, Henrica Mj
dc.creatorAshton, Katie
dc.creatorOtton, Geoffrey
dc.creatorProietto, Tony
dc.creatorLiu, Tao
dc.creatorMints, Miriam
dc.creatorTham, Emma
dc.creatorRENDOCAS
dc.creatorConsortium, Chibcha
dc.creatorJun Li, Mulin
dc.creatorYip, Shun H
dc.creatorWang, Junwen
dc.creatorBolla, Manjeet K
dc.creatorMichailidou, Kyriaki
dc.creatorWang, Qin
dc.creatorTyrer, Jonathan P
dc.creatorDunlop, Malcolm
dc.creatorHoulston, Richard
dc.creatorPalles, Claire
dc.creatorHopper, John L
dc.creatorAOCS Group
dc.creatorPeto, Julian
dc.creatorSwerdlow, Anthony J
dc.creatorBurwinkel, Barbara
dc.creatorBrenner, Hermann
dc.creatorMeindl, Alfons
dc.creatorBrauch, Hiltrud
dc.creatorLindblom, Annika
dc.creatorChang-Claude, Jenny
dc.creatorCouch, Fergus J
dc.creatorGiles, Graham G
dc.creatorKristensen, Vessela N
dc.creatorCox, Angela
dc.creatorCunningham, Julie M
dc.creatorPharoah, Paul DP
dc.creatorDunning, Alison M
dc.creatorEdwards, Stacey L
dc.creatorEaston, Douglas F
dc.creatorTomlinson, Ian
dc.creatorSpurdle, Amanda B
dc.date2016-05-18T15:18:27Z
dc.date2016-05-18T15:18:27Z
dc.date2016-06
dc.date.accessioned2026-08-03T02:23:47Z
dc.descriptionWe 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 r(2) = 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.descriptionI.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.descriptionThis is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/ng.3562
dc.formatapplication/pdf
dc.identifierCheng et al. Nature Genetics (2016). doi: 10.1038/ng.3562
dc.identifier1061-4036
dc.identifierhttps://www.repository.cam.ac.uk/handle/1810/256057
dc.identifier1546-1718
dc.identifier.urihttps://repo.dare.co.zw/handle/123456789/166413
dc.languageEnglish
dc.languageeng
dc.publisherSpringer Nature
dc.publisherhttps://doi.org/10.1038/ng.3562
dc.rightsAll rights reserved
dc.rightshttp://purl.org/NET/rdflicense/allrightsreserved
dc.subjectChromosomes, Human, Pair 8
dc.subjectEndometrial Neoplasms
dc.subjectFemale
dc.subjectGenetic Predisposition to Disease
dc.subjectGenome-Wide Association Study
dc.subjectHumans
dc.subjectPolymorphism, Single Nucleotide
dc.subjectPromoter Regions, Genetic
dc.titleFive endometrial cancer risk loci identified through genome-wide association analysis.
dc.typeArticle

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