SORA

Advancing, promoting and sharing knowledge of health through excellence in teaching, clinical practice and research into the prevention and treatment of illness

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

Cheng, THT; Thompson, DJ; O'Mara, TA; Painter, JN; Glubb, DM; Flach, S; Lewis, A; French, JD; Freeman-Mills, L; Church, D; et al. Cheng, THT; Thompson, DJ; O'Mara, TA; Painter, JN; Glubb, DM; Flach, S; Lewis, A; French, JD; Freeman-Mills, L; Church, D; Gorman, M; Martin, L; National Study of Endometrial Cancer Genetics Group (NSECG); Hodgson, S; Webb, PM; Australian National Endometrial Cancer Study Group (ANECS); Attia, J; Holliday, EG; McEvoy, M; Scott, RJ; Henders, AK; Martin, NG; Montgomery, GW; Nyholt, DR; Ahmed, S; Healey, CS; Shah, M; Dennis, J; Fasching, PA; Beckmann, MW; Hein, A; Ekici, AB; Hall, P; Czene, K; Darabi, H; Li, J; Dörk, T; Dürst, M; Hillemanns, P; Runnebaum, I; Amant, F; Schrauwen, S; Zhao, H; Lambrechts, D; Depreeuw, J; Dowdy, SC; Goode, EL; Fridley, BL; Winham, SJ; Njølstad, TS; Salvesen, HB; Trovik, J; Werner, HMJ; Ashton, K; Otton, G; Proietto, T; Liu, T; Mints, M; Tham, E; RENDOCAS; CHIBCHA Consortium; Li, MJ; Yip, SH; Wang, J; Bolla, MK; Michailidou, K; Wang, Q; Tyrer, JP; Dunlop, M; Houlston, R; Palles, C; Hopper, JL; AOCS Group; Peto, J; Swerdlow, AJ; Burwinkel, B; Brenner, H; Meindl, A; Brauch, H; Lindblom, A; Chang-Claude, J; Couch, FJ; Giles, GG; Kristensen, VN; Cox, A; Cunningham, JM; Pharoah, PDP; Dunning, AM; Edwards, SL; Easton, DF; Tomlinson, I; Spurdle, AB (2016) Five endometrial cancer risk loci identified through genome-wide association analysis. Nature Genetics, 48 (6). pp. 667-674. https://doi.org/10.1038/ng.3562
SGUL Authors: Hodgson, Shirley Victoria

[img]
Preview
PDF Accepted Version
Available under License ["licenses_description_publisher" not defined].

Download (5MB) | Preview

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.

Item Type: Article
Additional Information: Accepted manuscript made available for non commercial academic use only. Articles published by Nature Publishing Group (NPG) which are made available through academic repositories remain subject to copyright. Any reuse is subject to permission from NPG.
Keywords: National Study of Endometrial Cancer Genetics Group (NSECG), Australian National Endometrial Cancer Study Group (ANECS), RENDOCAS, CHIBCHA Consortium, AOCS Group, Developmental Biology, 11 Medical And Health Sciences, 06 Biological Sciences
SGUL Research Institute / Research Centre: Academic Structure > Molecular and Clinical Sciences Research Institute (MCS)
Academic Structure > Molecular and Clinical Sciences Research Institute (MCS) > Cell Sciences (INCCCS)
Journal or Publication Title: Nature Genetics
Language: eng
Dates:
DateEvent
June 2016Published
2 May 2016Published Online
8 April 2016Accepted
Publisher License: Publisher's own licence
PubMed ID: 27135401
Web of Science ID: WOS:000376744200015
Go to PubMed abstract
URI: https://openaccess.sgul.ac.uk/id/eprint/108148
Publisher's version: https://doi.org/10.1038/ng.3562

Actions (login required)

Edit Item Edit Item