GWAS meta-analysis and replication identifies three new susceptibility loci for ovarian cancer

Pharoah PDP, Tsai YY, Ramus SJ, Phelan CM, Goode EL, Lawrenson K, Buckley M, Fridley BL, Tyrer JP, Shen H, Weber R, Karevan R, Larson MC, Song H, Tessier DC, Bacot F, Vincent D, Cunningham JM, Dennis J, Dicks E, Aben KK, Anton-Culver H, Antonenkova N, Armasu SM, Baglietto L, Bandera EV, Beckmann M, Birrer MJ, Bloom G, Bogdanova N, Brenton JD, Brinton LA, Brooks-Wilson A, Brown R, Butzow R, Campbell I, Carney ME, Carvalho RS, Chang-Claude J, Chen YA, Chen Z, Chow WH, Cicek MS, Coetzee G, Cook LS, Cramer DW, Cybulski C, Dansonka-Mieszkowska A, Despierre E, Doherty JA, Doerk T, Du Bois A, Duerst M, Eccles D, Edwards R, Ekici AB, Fasching P, Fenstermacher D, Flanagan J, Gao YT, Garcia-Closas M, Gentry-Maharaj A, Giles G, Gjyshi A, Gore M, Gronwald J, Guo Q, Halle MK, Harter P, Hein A, Heitz F, Hillemanns P, Hoatlin M, Hogdall E, Hogdall CK, Hosono S, Jakubowska A, Jensen A, Kalli KR, Karlan BY, Kelemen LE, Kiemeney LA, Kjaer SK, Konecny GE, Krakstad C, Kupryjanczyk J, Lambrechts D, Lambrechts S, Le ND, Lee N, Lee J, Leminen A, Lim BK, Lissowska J, Lubinski J, Lundvall L, Lurie G, Massuger LFAG, Matsuo K, Mcguire V, Mclaughlin JR, Menon U, Modugno F, Moysich KB, Nakanishi T, Narod SA, Ness RB, Nevanlinna H, Nickels S, Noushmehr H, Odunsi K, Olson S, Orlow I, Paul J, Pejovic T, Pelttari LM, Permuth-Wey J, Pike MC, Poole EM, Qu X, Risch HA, Rodriguez-Rodriguez L, Rossing MA, Rudolph A, Runnebaum I, Rzepecka IK, Salvesen HB, Schwaab I, Severi G, Shen H, Shridhar V, Shu XO, Sieh W, Southey MC, Spellman P, Tajima K, Teo SH, Terry KL, Thompson PJ, Timorek A, Tworoger SS, Van Altena AM, Van Den Berg D, Vergote I, Vierkant RA, Vitonis AF, Wang-Gohrke S, Wentzensen N, Whittemore AS, Wik E, Winterhoff B, Woo YL, Wu AH, Yang HP, Zheng W, Ziogas A, Zulkifli F, Goodman MT, Hall P, Easton DF, Pearce CL, Berchuck A, Chenevix-Trench G, Iversen E, Monteiro ANA, Gayther SA, Schildkraut JM, Sellers TA (2013)

Publication Type: Journal article

Publication year: 2013

Journal

Book Volume: 45

Pages Range: 362-370

Journal Issue: 4

DOI: 10.1038/ng.2564

Abstract

Genome-wide association studies (GWAS) have identified four susceptibility loci for epithelial ovarian cancer (EOC), with another two suggestive loci reaching near genome-wide significance. We pooled data from a GWAS conducted in North America with another GWAS from the UK. We selected the top 24,551 SNPs for inclusion on the iCOGS custom genotyping array. We performed follow-up genotyping in 18,174 individuals with EOC (cases) and 26,134 controls from 43 studies from the Ovarian Cancer Association Consortium. We validated the two loci at 3q25 and 17q21 that were previously found to have associations close to genome-wide significance and identified three loci newly associated with risk: two loci associated with all EOC subtypes at 8q21 (rs11782652, P = 5.5 × 10^-9) and 10p12 (rs1243180, P = 1.8 × 10^-8) and another locus specific to the serous subtype at 17q12 (rs757210, P = 8.1 × 10^-10). An integrated molecular analysis of genes and regulatory regions at these loci provided evidence for functional mechanisms underlying susceptibility and implicated CHMP4C in the pathogenesis of ovarian cancer.

Authors with CRIS profile

Involved external institutions

University of Cambridge United Kingdom (GB) University of South Florida (USF) United States (USA) (US) University of Southern California (USC) United States (USA) (US) Mayo Clinic United States (USA) (US) Duke University United States (USA) (US) McGill University Canada (CA) 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) Cancer Council Victoria Australia (AU) University of Medicine and Dentistry of New Jersey (UMDNJ) United States (USA) (US) Harvard University United States (USA) (US) Medizinische Hochschule Hannover (MHH) / Hannover Medical School Germany (DE) National Cancer Institute (NCI) United States (USA) (US) British Columbia Cancer Agency Canada (CA) Imperial College London / The Imperial College of Science, Technology and Medicine United Kingdom (GB) Helsingin yliopisto / University of Helsinki Finland (FI) Peter MacCallum Cancer Centre Australia (AU) University of Hawaii (U.H.) United States (USA) (US) Deutsches Krebsforschungszentrum (DKFZ) Germany (DE) University of New Mexico (UNM) / Universidad de Nuevo México United States (USA) (US) Brigham and Women's Hospital (BWH) United States (USA) (US) Pomeranian Medical University / Pomorski Uniwersytet Medyczny w Szczecinie (PMU) Poland (PL) 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) Dartmouth College United States (USA) (US) Universitätsklinikum Jena Germany (DE) University of Southampton United Kingdom (GB) University of Pittsburgh United States (USA) (US) Shanghai Cancer Institute / 上海市肿瘤研究所 China (CN) The Institute of Cancer Research (ICR) United Kingdom (GB) Royal Marsden Hospital / The Royal Marsden NHS Foundation Trust United Kingdom (GB) Haukeland University Hospital / Haukeland universitetssykehus Norway (NO) HELIOS Kliniken Germany (DE) Oregon Health and Science University (OSHU) United States (USA) (US) Danish Cancer Society Research Center Denmark (DK) Rigshospitalet Denmark (DK) Aichi Cancer Center Research Institute Japan (JP) University College London (UCL) United Kingdom (GB) Roswell Park Cancer Institute United States (USA) (US) Yale University United States (USA) (US) The University of Melbourne Australia (AU) Cedars-Sinai Medical Center United States (USA) (US) Alberta Health Services (AHS) Canada (CA) University of California Los Angeles (UCLA) United States (USA) (US) University of Malaya (UM) / Universiti Malaya Malaysia (MY) Stanford University United States (USA) (US) University of Toronto Canada (CA) University of Texas Health Science Center at Houston (UTHealth) United States (USA) (US) Memorial Sloan Kettering Cancer Center United States (USA) (US) Beatson West of Scotland Cancer Centre (BWSCC) United Kingdom (GB) University of Washington United States (USA) (US) Institut für Humangenetik Wiesbaden Germany (DE) Vanderbilt University United States (USA) (US) Cancer Research Initiatives Foundation (CARIF) / Cancer Research Malaysia (CRM) Malaysia (MY) Wrocław Medical University / Uniwersytet Medyczny we Wrocławiu Poland (PL) Universität Ulm Germany (DE) Karolinska Institute Sweden (SE) QIMR Berghofer Medical Research Institute (früher: the Queensland Institute of Medical Research) Australia (AU)

How to cite

APA:

Pharoah, P.D.P., Tsai, Y.-Y., Ramus, S.J., Phelan, C.M., Goode, E.L., Lawrenson, K.,... Sellers, T.A. (2013). GWAS meta-analysis and replication identifies three new susceptibility loci for ovarian cancer. Nature Genetics, 45(4), 362-370. https://doi.org/10.1038/ng.2564

MLA:

Pharoah, Paul D. P., et al. "GWAS meta-analysis and replication identifies three new susceptibility loci for ovarian cancer." Nature Genetics 45.4 (2013): 362-370.

BibTeX: Download