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

Title: GWAS meta-analysis and replication identifies three new susceptibility loci for ovarian cancer
Authors: Pharoah, PDP
Tsai, Y-Y
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, MW
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, W-H
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, PA
Fenstermacher, D
Flanagan, J
Gao, Y-T
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, X-O
Sieh, W
Southey, MC
Spellman, P
Tajima, K
Teo, S-H
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
Item Type: Journal Article
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.
Issue Date: 27-Mar-2013
Date of Acceptance: 30-Jan-2013
URI: http://hdl.handle.net/10044/1/40814
DOI: http://dx.doi.org/10.1038/ng.2564
ISSN: 1546-1718
Publisher: Nature Publishing Group
Start Page: 362
End Page: 370
Journal / Book Title: Nature Genetics
Volume: 45
Issue: 4
Copyright Statement: © 2013 Nature America, Inc. All rights reserved.
Sponsor/Funder: Cancer Research UK
Funder's Grant Number: C536/A13086
Keywords: Science & Technology
Life Sciences & Biomedicine
Genetics & Heredity
GENETICS & HEREDITY
GENOME-WIDE ASSOCIATION
RISK
GENE
EXPRESSION
CARCINOMA
NEBULETTE
LEUKEMIA
CELLS
19P13
MYC
Case-Control Studies
Cooperative Behavior
Cystadenocarcinoma, Serous
Female
Gene-Environment Interaction
Genetic Loci
Genetic Predisposition to Disease
Genome-Wide Association Study
Genotype
Humans
Meta-Analysis as Topic
Neoplasm Invasiveness
Ovarian Neoplasms
Polymorphism, Single Nucleotide
Risk Factors
Australian Cancer Study
Australian Ovarian Cancer Study Group
Developmental Biology
11 Medical And Health Sciences
06 Biological Sciences
Publication Status: Published
Appears in Collections:Division of Surgery
Division of Cancer
Faculty of Medicine



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