Five endometrial cancer risk loci identified through genome-wide association analysis View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2016-06

AUTHORS

Timothy HT Cheng, Deborah J Thompson, Tracy A O’Mara, Jodie N Painter, Dylan M Glubb, Susanne Flach, Annabelle Lewis, Juliet D French, Luke Freeman-Mills, David Church, Maggie Gorman, Lynn Martin, , Shirley Hodgson, Penelope M Webb, , John Attia, Elizabeth G Holliday, Mark McEvoy, Rodney J Scott, Anjali K Henders, Nicholas G Martin, Grant W Montgomery, Dale R Nyholt, Shahana Ahmed, Catherine S Healey, Mitul Shah, Joe Dennis, Peter A Fasching, Matthias W Beckmann, Alexander Hein, Arif B Ekici, Per Hall, Kamila Czene, Hatef Darabi, Jingmei Li, Thilo Dörk, Matthias Dürst, Peter Hillemanns, Ingo Runnebaum, Frederic Amant, Stefanie Schrauwen, Hui Zhao, Diether Lambrechts, Jeroen Depreeuw, Sean C Dowdy, Ellen L Goode, Brooke L Fridley, Stacey J Winham, Tormund S Njølstad, Helga B Salvesen, Jone Trovik, Henrica MJ Werner, Katie Ashton, Geoffrey Otton, Tony Proietto, Tao Liu, Miriam Mints, Emma Tham, , CHIBCHA Consortium, Mulin Jun Li, Shun H Yip, Junwen Wang, Manjeet K Bolla, Kyriaki Michailidou, Qin Wang, Jonathan P Tyrer, Malcolm Dunlop, Richard Houlston, Claire Palles, John L Hopper, , Julian Peto, Anthony J Swerdlow, Barbara Burwinkel, Hermann Brenner, Alfons Meindl, Hiltrud Brauch, Annika Lindblom, Jenny Chang-Claude, Fergus J Couch, Graham G Giles, Vessela N Kristensen, Angela Cox, Julie M Cunningham, Paul D P Pharoah, Alison M Dunning, Stacey L Edwards, Douglas F Easton, Ian Tomlinson, Amanda B Spurdle

ABSTRACT

We 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. More... »

PAGES

667-674

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/ng.3562

    DOI

    http://dx.doi.org/10.1038/ng.3562

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1002700757

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/27135401


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