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

Beitrag in einer Fachzeitschrift


Details zur Publikation

Autor(en): 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 PA, 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
Zeitschrift: Nature Genetics
Jahr der Veröffentlichung: 2016
Band: 48
Heftnummer: 6
Seitenbereich: 667-74
ISSN: 1061-4036


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.



FAU-Autoren / FAU-Herausgeber

Beckmann, Matthias Prof. Dr.
Lehrstuhl für Geburtshilfe und Frauenheilkunde
Ekici, Arif Bülent Dr. rer. nat.
Humangenetisches Institut
Fasching, Peter PD Dr.
Professur für Translationale Frauenheilkunde und Geburtshilfe
Hein, Alexander PD Dr.
Frauenklinik


Autor(en) der externen Einrichtung(en)
Deutsches Krebsforschungszentrum (DKFZ)
Flanders Institute for Biotechnology / Vlaams Instituut voor Biotechnologie (VIB)
Friedrich-Schiller-Universität Jena
Hannover Medical School / Medizinische Hochschule Hannover (MHH)
John Hunter Hospital
Karolinska Institute
Karolinska University Hospital / Karolinska Universitetssjukhuset
Katholieke Universiteit Leuven (KUL) / Catholic University of Leuven
London School of Hygiene and Tropical Medicine
Mayo Clinic
Oslo University Hospital / Oslo Universitetssykehus
QIMR Berghofer Medical Research Institute (früher: the Queensland Institute of Medical Research)
Robert-Bosch-Krankenhaus
Ruprecht-Karls-Universität Heidelberg
St George's, University of London (SGUL) / St George's Hospital Medical School
Technische Universität München (TUM)
The Institute of Cancer Research (ICR)
The University of Melbourne
University of Bergen
University of Cambridge
University of Edinburgh
University of Hong Kong (HKU) / 香港大學
University of Kansas (KU)
University of Newcastle (UoN)
University of Oxford
University of Sheffield


Zitierweisen

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.

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Zuletzt aktualisiert 2018-07-10 um 02:14