Genome-wide association study of subtype-specific epithelial ovarian cancer risk alleles using pooled DNA

Earp MA, Kelemen LE, Magliocco AM, Swenerton KD, Chenevix-Trench G, Lu Y, Hein A, Ekici AB, Beckmann M, Fasching P, Lambrechts D, Despierre E, Vergote I, Lambrechts S, Doherty JA, Rossing MA, Chang-Claude J, Rudolph A, Friel G, Moysich KB, Odunsi K, Sucheston-Campbell L, Lurie G, Goodman MT, Carney ME, Thompson PJ, Runnebaum IB, Duerst M, Hillemanns P, Doerk T, Antonenkova N, Bogdanova N, Leminen A, Nevanlinna H, Pelttari LM, Butzow R, Bunker CH, Modugno F, Edwards RP, Ness RB, Du Bois A, Heitz F, Schwaab I, Harter P, Karlan BY, Walsh C, Lester J, Jensen A, Kjaer SK, Hogdall CK, Hogdall E, Lundvall L, Sellers TA, Fridley BL, Goode EL, Cunningham JM, Vierkant RA, Giles GG, Baglietto L, Severi G, Southey MC, Liang D, Wu X, Lu K, Hildebrandt MAT, Levine DA, Bisogna M, Schildkraut JM, Iversen ES, Weber RP, Berchuck A, Cramer DW, Terry KL, Poole EM, Tworoger SS, Bandera EV, Chandran U, Orlow I, Olson SH, Wik E, Salvesen HB, Bjorge L, Halle MK, Van Altena AM, Aben KKH, Kiemeney LA, Massuger LFAG, Pejovic T, Bean YT, Cybulski C, Gronwald J, Lubinski J, Wentzensen N, Brinton LA, Lissowska J, Garcia-Closas M, Dicks E, Dennis J, Easton DF, Song H, Tyrer JP, Pharoah PDP, Eccles D, Campbell IG, Whittemore AS, Mcguire V, Sieh W, Rothstein JH, Flanagan JM, Paul J, Brown R, Phelan CM, Risch HA, Mclaughlin JR, Narod SA, Ziogas A, Anton-Culver H, Gentry-Maharaj A, Menon U, Gayther SA, Ramus SJ, Wu AH, Pearce CL, Pike MC, Dansonka-Mieszkowska A, Rzepecka IK, Szafron LM, Kupryjanczyk J, Cook LS, Le ND, Brooks-Wilson A (2014)

Publication Type: Journal article

Publication year: 2014

Journal

Publisher: Springer Verlag (Germany)

Book Volume: 133

Pages Range: 481-97

Journal Issue: 5

DOI: 10.1007/s00439-013-1383-3

Abstract

Epithelial ovarian cancer (EOC) is a heterogeneous cancer with both genetic and environmental risk factors. Variants influencing the risk of developing the less-common EOC subtypes have not been fully investigated. We performed a genome-wide association study (GWAS) of EOC according to subtype by pooling genomic DNA from 545 cases and 398 controls of European descent, and testing for allelic associations. We evaluated for replication 188 variants from the GWAS [56 variants for mucinous, 55 for endometrioid and clear cell, 53 for low-malignant potential (LMP) serous, and 24 for invasive serous EOC], selected using pre-defined criteria. Genotypes from 13,188 cases and 23,164 controls of European descent were used to perform unconditional logistic regression under the log-additive genetic model; odds ratios (OR) and 95 % confidence intervals are reported. Nine variants tagging six loci were associated with subtype-specific EOC risk at P < 0.05, and had an OR that agreed in direction of effect with the GWAS results. Several of these variants are in or near genes with a biological rationale for conferring EOC risk, including ZFP36L1 and RAD51B for mucinous EOC (rs17106154, OR = 1.17, P = 0.029, n = 1,483 cases), GRB10 for endometrioid and clear cell EOC (rs2190503, P = 0.014, n = 2,903 cases), and C22orf26/BPIL2 for LMP serous EOC (rs9609538, OR = 0.86, P = 0.0043, n = 892 cases). In analyses that included the 75 GWAS samples, the association between rs9609538 (OR = 0.84, P = 0.0007) and LMP serous EOC risk remained statistically significant at P < 0.0012 adjusted for multiple testing. Replication in additional samples will be important to verify these results for the less-common EOC subtypes.

Authors with CRIS profile

Involved external institutions

British Columbia Cancer Agency Canada (CA) University of South Florida (USF) United States (USA) (US) University of British Columbia Canada (CA) QIMR Berghofer Medical Research Institute (früher: the Queensland Institute of Medical Research) Australia (AU) Katholieke Universiteit Leuven (KUL) / Catholic University of Leuven Belgium (BE) Friedrich-Schiller-Universität Jena Germany (DE) Roswell Park Cancer Institute United States (USA) (US) University of Hawaii (U.H.) United States (USA) (US) University of Pittsburgh United States (USA) (US) Kliniken Essen-Mitte Germany (DE) Cedars-Sinai Medical Center United States (USA) (US) Medizinische Hochschule Hannover (MHH) / Hannover Medical School Germany (DE) Duke University United States (USA) (US) Danish Cancer Society Denmark (DK) Copenhagen University Hospital Denmark (DK) N.N. Alexandrov National Cancer Centre of Belarus for Oncology and Medical Radiology Belarus (BY) Institut für Humangenetik Wiesbaden Germany (DE) Cancer Council Victoria Australia (AU) University of Texas MD Anderson Cancer Center United States (USA) (US) Harvard University United States (USA) (US) Brigham and Women's Hospital (BWH) United States (USA) (US) Rutgers Cancer Institute of New Jersey United States (USA) (US) Haukeland University Hospital / Haukeland universitetssykehus Norway (NO) University of Bergen / Universitetet i Bergen Norway (NO) Radboud University Nijmegen Netherlands (NL) University of Cambridge United Kingdom (GB) Pomeranian Medical University / Pomorski Uniwersytet Medyczny w Szczecinie (PMU) Poland (PL) University College London (UCL) United Kingdom (GB) Peter MacCallum Cancer Centre Australia (AU) National Cancer Institute (NCI) United States (USA) (US) Imperial College London / The Imperial College of Science, Technology and Medicine United Kingdom (GB) University of Toronto Canada (CA) University of Southern California (USC) United States (USA) (US) Memorial Sloan Kettering Cancer Center United States (USA) (US) Maria Skłodowska-Curie Institute of Oncology / Centrum Onkologii–Instytut im. Marii Skłodowskiej-Curie w Warszawie Poland (PL) Alberta Health Services (AHS) Canada (CA) Mount Sinai Hospital (MSH) Canada (CA) Stanford University United States (USA) (US) Beatson West of Scotland Cancer Centre (BWSCC) United Kingdom (GB) Oregon Health and Science University (OSHU) United States (USA) (US) Mayo Clinic United States (USA) (US) University of Kansas (KU) United States (USA) (US) Helsingin yliopisto / University of Helsinki Finland (FI) Fred Hutchinson Cancer Research Center United States (USA) (US) Texas Southern University (TSU) United States (USA) (US) Flanders Institute for Biotechnology / Vlaams Instituut voor Biotechnologie (VIB) Belgium (BE) The University of Melbourne Australia (AU) Deutsches Krebsforschungszentrum (DKFZ) Germany (DE) University of California Irvine United States (USA) (US) University of Southampton United Kingdom (GB) Dartmouth College United States (USA) (US) Yale University United States (USA) (US)

How to cite

APA:

Earp, M.A., Kelemen, L.E., Magliocco, A.M., Swenerton, K.D., Chenevix-Trench, G., Lu, Y.,... Brooks-Wilson, A. (2014). Genome-wide association study of subtype-specific epithelial ovarian cancer risk alleles using pooled DNA. Human genetics, 133(5), 481-97. https://doi.org/10.1007/s00439-013-1383-3

MLA:

Earp, Madalene A., et al. "Genome-wide association study of subtype-specific epithelial ovarian cancer risk alleles using pooled DNA." Human genetics 133.5 (2014): 481-97.

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