Genome-wide significant risk associations for mucinous ovarian carcinoma

Kelemen LE, Lawrenson K, Tyrer J, Li Q, Lee JM, Seo JH, Phelan CM, Beesley J, Chen X, Spindler TJ, Aben KKH, Anton-Culver H, Antonenkova N, Baker H, Bandera EV, Bean Y, Beckmann M, Bisogna M, Bjorge L, Bogdanova N, Brinton LA, Brooks-Wilson A, Bruinsma F, Butzow R, Campbell IG, Carty K, Chang-Claude J, Chen YA, Chen Z, Cook LS, Cramer DW, Cunningham JM, Cybulski C, Dansonka-Mieszkowska A, Dennis J, Dicks E, Doherty JA, Dicks E, Doherty JA, Doerk T, Du Bois A, Duerst M, Eccles D, Easton DT, Edwards RP, Eilber U, Ekici AB, Engelholm SA, Fasching P, Fridley BL, Gao YT, Gentry-Maharaj A, Giles GG, Glasspool R, Goode EL, Goodman MT, Grownwald J, Harrington P, Harter P, Hasmad HN, Hein A, Heitz F, Hildebrandt MAT, Hillemanns P, Hogdall E, Hogdall C, Hosono S, Iversen ES, Jakubowska A, Jensen A, Ji BT, Karlan BY, Kellar M, Kelley JL, Kiemeney LA, Krakstad C, Kjaer SK, Kupryjanczyk J, Lambrechts D, Lambrechts S, Le ND, Lee AW, Lele S, Leminen A, Lester J, Levine DA, Liang D, Lissowska J, Lu K, Lubinski J, Lundvall L, Massuger LFAG, Matsuo K, Mcguire V, Mclaughlin JR, Mcneish I, Menon U, Modugno F, Moes-Sosnowska J, Moysich KB, Narod SA, Nedergaard L, Ness RB, Nevanlinna H, Adenan NAM, Odunsi K, Olson SH, Orlow I, Orsulic S, Weber RP, Paul J, Pearce CL, Pejovic T, Pelttari LM, Permuth-Wey J, Pike MC, Poole EM, Ramus SJ, Risch HA, Rosen B, Rossing MA, Rothstein JH, Rudolph A, Runnebaum IB, Rzepecka IK, Salvesen HB, Schildkraut JM, Schwaab I, Shu XO, Shvetsov YB, Siddiqui N, Sieh W, Song H, Southey MC, Sucheston L, Tangen IL, Teo SH, Terry KL, Thompson PJ, Tworoger SS, Van Altena AM, Van Nieuwenhuysen E, Vergote I, Vierkant RA, Wang-Gohrke S, Walsh C, Wentzensen N, Whittemore AS, Wicklund KG, Wilkens LR, Sawicki W, Woo YL, Wu X, Wu AH, Yang H, Zheng W, Ziogas A, Sellers TA, Freedman ML, Chenevix-Trench G, Pharoah PDP, Gayther SA, Berchuck A (2015)

Publication Type: Journal article

Publication year: 2015

Journal

Book Volume: 47

Pages Range: 888-897

Journal Issue: 8

DOI: 10.1038/ng.3336

Abstract

Genome-wide association studies have identified several risk associations for ovarian carcinomas but not for mucinous ovarian carcinomas (MOCs). Our analysis of 1,644 MOC cases and 21,693 controls with imputation identified 3 new risk associations: rs752590 at 2q13 (P = 3.3 × 10^-8), rs711830 at 2q31.1 (P = 7.5 × 10^-12) and rs688187 at 19q13.2 (P = 6.8 × 10^-13). We identified significant expression quantitative trait locus (eQTL) associations for HOXD9 at 2q31.1 in ovarian (P = 4.95 × 10^-4, false discovery rate (FDR) = 0.003) and colorectal (P = 0.01, FDR = 0.09) tumors and for PAX8 at 2q13 in colorectal tumors (P = 0.03, FDR = 0.09). Chromosome conformation capture analysis identified interactions between the HOXD9 promoter and risk-associated SNPs at 2q31.1. Overexpressing HOXD9 in MOC cells augmented the neoplastic phenotype. These findings provide the first evidence for MOC susceptibility variants and insights into the underlying biology of the disease.

Authors with CRIS profile

Involved external institutions

Xiamen University China (CN) Deutsches Krebsforschungszentrum (DKFZ) Germany (DE) Friedrich-Schiller-Universität Jena Germany (DE) Medical University of South Carolina (MUSC) United States (USA) (US) University of Southern California (USC) United States (USA) (US) University of Cambridge United Kingdom (GB) Dana–Farber Cancer Institute United States (USA) (US) H. Lee Moffitt Cancer Center & Research Institute United States (USA) (US) QIMR Berghofer Medical Research Institute (früher: the Queensland Institute of Medical Research) Australia (AU) Radboud University Nijmegen Netherlands (NL) University of California Irvine United States (USA) (US) N.N. Alexandrov National Cancer Centre of Belarus for Oncology and Medical Radiology Belarus (BY) Rutgers, The State University of New Jersey United States (USA) (US) Oregon Health and Science University (OSHU) United States (USA) (US) Memorial Sloan Kettering Cancer Center United States (USA) (US) Haukeland University Hospital / Haukeland universitetssykehus Norway (NO) Medizinische Hochschule Hannover (MHH) / Hannover Medical School Germany (DE) National Cancer Institute (NCI) United States (USA) (US) British Columbia Cancer Agency Canada (CA) Cancer Council Victoria Australia (AU) Helsingin yliopisto / University of Helsinki Finland (FI) Peter MacCallum Cancer Centre Australia (AU) Beatson West of Scotland Cancer Centre (BWSCC) United Kingdom (GB) University of New Mexico (UNM) / Universidad de Nuevo México United States (USA) (US) Harvard University United States (USA) (US) Mayo Clinic United States (USA) (US) West Pomeranian University of Technology Szczecin / Zachodniopomorski Uniwersytet Technologiczny w Szczecinie (ZUT) Poland (PL) Dartmouth College United States (USA) (US) Kliniken Essen-Mitte Germany (DE) University of Southampton United Kingdom (GB) University of Pittsburgh United States (USA) (US) University of Copenhagen Denmark (DK) Shanghai Cancer Institute / 上海市肿瘤研究所 China (CN) University College London (UCL) United Kingdom (GB) Cedars-Sinai Medical Center United States (USA) (US) Cancer Research Initiatives Foundation (CARIF) / Cancer Research Malaysia (CRM) Malaysia (MY) University of Texas MD Anderson Cancer Center United States (USA) (US) Danish Cancer Society Research Center Denmark (DK) Maria Skłodowska-Curie Institute of Oncology / Centrum Onkologii–Instytut im. Marii Skłodowskiej-Curie w Warszawie Poland (PL) Katholieke Universiteit Leuven (KUL) / Catholic University of Leuven Belgium (BE) University Hospital Leuven (UZ) / Universitaire ziekenhuizen Leuven Belgium (BE) University of Kansas (KU) United States (USA) (US) Aichi Cancer Center Research Institute Japan (JP) Duke University United States (USA) (US) Universität Ulm Germany (DE) Wrocław Medical University / Uniwersytet Medyczny we Wrocławiu Poland (PL) University of Malaya (UM) / Universiti Malaya Malaysia (MY) Roswell Park Cancer Institute United States (USA) (US) Helsinki University Central Hospital (HUCH) / Helsingin seudun yliopistollinen keskussairaala (HYKS) Finland (FI) Texas Southern University (TSU) United States (USA) (US) Kyushu University / 九州大学 Japan (JP) Stanford University United States (USA) (US) Public Health Ontario Canada (CA) University of Glasgow United Kingdom (GB) University of Toronto Canada (CA) Yale University United States (USA) (US) Fred Hutchinson Cancer Research Center United States (USA) (US) Vanderbilt University United States (USA) (US) University of Hawaii (U.H.) United States (USA) (US) Glasgow Royal Infirmary (GRI) United Kingdom (GB) The University of Melbourne Australia (AU)

How to cite

APA:

Kelemen, L.E., Lawrenson, K., Tyrer, J., Li, Q., Lee, J.M., Seo, J.-H.,... Berchuck, A. (2015). Genome-wide significant risk associations for mucinous ovarian carcinoma. Nature Genetics, 47(8), 888-897. https://doi.org/10.1038/ng.3336

MLA:

Kelemen, Linda E., et al. "Genome-wide significant risk associations for mucinous ovarian carcinoma." Nature Genetics 47.8 (2015): 888-897.

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