Cheng, T.H.T., Thompson, D.J., O’Mara, T.A. et al. (23 more authors) (2016) Five endometrial cancer risk loci identified through genome-wide association analysis. Nature Genetics, 48. pp. 667-674. ISSN 1061-4036, ESSN: 1546-1718
Abstract
We conducted a meta-analysis of three endometrial cancer (EC) GWAS and two replication phases totaling 7,737 EC cases and 37,144 controls of European ancestry. Genome-wide imputation and meta-analysis identified five novel risk loci at 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). A second independent 8q24.21 signal (rs17232730) was found. Functional studies of the intergenic 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 EC protective allele suppressed gene expression in vitro suggesting that the regulation of KLF5 expression, a gene linked to uterine development, is implicated in tumorigenesis. These findings provide enhanced insight into the genetic and biological basis of EC.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2016 Nature America, inc. This is an author produced version of a paper subsequently published in Nature Genetics. Uploaded in accordance with the publisher's self-archiving policy. |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > The Medical School (Sheffield) > Division of Genomic Medicine (Sheffield) > Department of Oncology and Metabolism (Sheffield) The University of Sheffield > Sheffield Teaching Hospitals |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 17 Mar 2016 15:15 |
Last Modified: | 03 Nov 2016 01:41 |
Published Version: | http://dx.doi.org/10.1038/ng.3562 |
Status: | Published |
Publisher: | Nature Publishing Group |
Refereed: | Yes |
Identification Number: | 10.1038/ng.3562 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:96422 |