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, Gorman M, Martin L, Hodgson S, Webb PM, 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 P, Beckmann M, Hein A, Ekici AB, Hall P, Czene K, Darabi H, Li J, Doerk T, Duerst M, Hillemanns P, Runnebaum I, Amant F, Schrauwen S, Zhao H, Lambrechts D, Depreeuw J, Dowdy SC, Goode EL, Fridley BL, Winham SJ, Njolstad TS, Salvesen HB, Trovik J, Werner HMJ, Ashton K, Otton G, Proietto T, Liu T, Mints M, Tham E, Li MJ, Yip SH, Wang J, Bolla MK, Michailidou K, Wang Q, Tyrer JP, Dunlop M, Houlston R, Palles C, Hopper JL, 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)

Publication Type: Journal article

Publication year: 2016

Journal

Book Volume: 48

Pages Range: 667-74

Journal Issue: 6

DOI: 10.1038/ng.3562

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.

Authors with CRIS profile

Involved external institutions

University of Cambridge United Kingdom (GB) University of Oxford United Kingdom (GB) QIMR Berghofer Medical Research Institute (früher: the Queensland Institute of Medical Research) Australia (AU) Mayo Clinic United States (USA) (US) University of Sheffield United Kingdom (GB) Oslo University Hospital / Oslo Universitetssykehus Rikshospitalet Norway (NO) The University of Melbourne Australia (AU) Deutsches Krebsforschungszentrum (DKFZ) Germany (DE) Karolinska Institute Sweden (SE) Robert-Bosch-Krankenhaus Germany (DE) Technische Universität München (TUM) Germany (DE) Ruprecht-Karls-Universität Heidelberg Germany (DE) The Institute of Cancer Research (ICR) United Kingdom (GB) London School of Hygiene and Tropical Medicine United Kingdom (GB) University of Edinburgh United Kingdom (GB) Karolinska University Hospital / Karolinska Universitetssjukhuset Sweden (SE) University of Hong Kong (HKU) / 香港大學 Hong Kong (HK) University of Newcastle (UoN) Australia (AU) John Hunter Hospital Australia (AU) University of Bergen / Universitetet i Bergen Norway (NO) University of Kansas (KU) United States (USA) (US) Katholieke Universiteit Leuven (KUL) / Catholic University of Leuven Belgium (BE) Flanders Institute for Biotechnology / Vlaams Instituut voor Biotechnologie (VIB) Belgium (BE) Friedrich-Schiller-Universität Jena Germany (DE) Medizinische Hochschule Hannover (MHH) / Hannover Medical School Germany (DE) St George's, University of London (SGUL) / St George's Hospital Medical School United Kingdom (GB)

How to cite

APA:

Cheng, T.H.T., Thompson, D.J., O'Mara, T.A., Painter, J.N., Glubb, D.M., Flach, S.,... Spurdle, A.B. (2016). Five endometrial cancer risk loci identified through genome-wide association analysis. Nature Genetics, 48(6), 667-74. https://dx.doi.org/10.1038/ng.3562

MLA:

Cheng, Timothy H. T., et al. "Five endometrial cancer risk loci identified through genome-wide association analysis." Nature Genetics 48.6 (2016): 667-74.

BibTeX: Download