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Identification and molecular characterization of a new ovarian cancer susceptibility locus at 17q21.31

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Title: Identification and molecular characterization of a new ovarian cancer susceptibility locus at 17q21.31
Authors: Permuth-Wey, J
Lawrenson, K
Shen, HC
Velkova, A
Tyrer, JP
Chen, Z
Lin, H-Y
Chen, YA
Tsai, Y-Y
Qu, X
Ramus, SJ
Karevan, R
Lee, J
Lee, N
Larson, MC
Aben, KK
Anton-Culver, H
Antonenkova, N
Antoniou, AC
Armasu, SM
Bacot, F
Baglietto, L
Bandera, EV
Barnholtz-Sloan, J
Beckmann, MW
Birrer, MJ
Bloom, G
Bogdanova, N
Brinton, LA
Brooks-Wilson, A
Brown, R
Butzow, R
Cai, Q
Campbell, I
Chang-Claude, J
Chanock, S
Chenevix-Trench, G
Cheng, JQ
Cicek, MS
Coetzee, GA
Cook, LS
Couch, FJ
Cramer, DW
Cunningham, JM
Dansonka-Mieszkowska, A
Despierre, E
Doherty, JA
Doerk, T
Du Bois, A
Duerst, M
Easton, DF
Eccles, D
Edwards, R
Ekici, AB
Fasching, PA
Fenstermacher, DA
Flanagan, JM
Garcia-Closas, M
Gentry-Maharaj, A
Giles, GG
Glasspool, RM
Gonzalez-Bosquet, J
Goodman, MT
Gore, M
Gorski, B
Gronwald, J
Hall, P
Halle, MK
Harter, P
Heitz, F
Hillemanns, P
Hoatlin, M
Hogdall, CK
Hogdall, E
Hosono, S
Jakubowska, A
Jensen, A
Jim, H
Kalli, KR
Karlan, BY
Kaye, SB
Kelemen, LE
Kiemeney, LA
Kikkawa, F
Konecny, GE
Krakstad, C
Kjaer, SK
Kupryjanczyk, J
Lambrechts, D
Lambrechts, S
Lancaster, JM
Le, ND
Leminen, A
Levine, DA
Liang, D
Lim, BK
Lin, J
Lissowska, J
Lu, KH
Lubinski, J
Lurie, G
Massuger, LFAG
Matsuo, K
McGuire, V
McLaughlin, JR
Menon, U
Modugno, F
Moysich, KB
Nakanishi, T
Narod, SA
Nedergaard, L
Ness, RB
Nevanlinna, H
Nickels, S
Noushmehr, H
Odunsi, K
Olson, SH
Orlow, I
Paul, J
Pearce, CL
Pejovic, T
Pelttari, LM
Pike, MC
Poole, EM
Raska, P
Renner, SP
Risch, HA
Rodriguez-Rodriguez, L
Rossing, MA
Rudolph, A
Runnebaum, IB
Rzepecka, IK
Salvesen, HB
Schwaab, I
Severi, G
Shridhar, V
Shu, X-O
Shvetsov, YB
Sieh, W
Song, H
Southey, MC
Spiewankiewicz, B
Stram, D
Sutphen, R
Teo, S-H
Terry, KL
Tessier, DC
Thompson, PJ
Tworoger, SS
Van Altena, AM
Vergote, I
Vierkant, RA
Vincent, D
Vitonis, AF
Wang-Gohrke, S
Weber, RP
Wentzensen, N
Whittemore, AS
Wik, E
Wilkens, LR
Winterhoff, B
Woo, YL
Wu, AH
Xiang, Y-B
Yang, HP
Zheng, W
Ziogas, A
Zulkifli, F
Phelan, CM
Iversen, E
Schildkraut, JM
Berchuck, A
Fridley, BL
Goode, EL
Pharoah, PDP
Monteiro, ANA
Sellers, TA
Gayther, SA
Item Type: Journal Article
Abstract: Epithelial ovarian cancer (EOC) has a heritable component that remains to be fully characterized. Most identified common susceptibility variants lie in non-protein-coding sequences. We hypothesized that variants in the 3′ untranslated region at putative microRNA (miRNA)-binding sites represent functional targets that influence EOC susceptibility. Here, we evaluate the association between 767 miRNA-related single-nucleotide polymorphisms (miRSNPs) and EOC risk in 18,174 EOC cases and 26,134 controls from 43 studies genotyped through the Collaborative Oncological Gene–environment Study. We identify several miRSNPs associated with invasive serous EOC risk (odds ratio=1.12, P=10−8) mapping to an inversion polymorphism at 17q21.31. Additional genotyping of non-miRSNPs at 17q21.31 reveals stronger signals outside the inversion (P=10−10). Variation at 17q21.31 is associated with neurological diseases, and our collaboration is the first to report an association with EOC susceptibility. An integrated molecular analysis in this region provides evidence for ARHGAP27 and PLEKHM1 as candidate EOC susceptibility genes.
Issue Date: 27-Mar-2013
Date of Acceptance: 18-Feb-2013
URI: http://hdl.handle.net/10044/1/40811
DOI: http://dx.doi.org/10.1038/ncomms2613
ISSN: 2041-1723
Publisher: Nature Publishing Group
Journal / Book Title: Nature Communications
Volume: 4
Copyright Statement: This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/3.0/
Sponsor/Funder: Cancer Research UK
Funder's Grant Number: C536/A13086
Keywords: Science & Technology
Multidisciplinary Sciences
Science & Technology - Other Topics
MULTIDISCIPLINARY SCIENCES
GENOME-WIDE ASSOCIATION
MICRORNA EXPRESSION
GENETIC-VARIANTS
FUNCTIONAL ANNOTATION
SITE POLYMORPHISMS
PARKINSON-DISEASE
COMMON INVERSION
BINDING-SITES
MAPT REGION
RISK
Chromosomes, Human, Pair 17
Female
Genetic Predisposition to Disease
Humans
Neoplasms, Glandular and Epithelial
Ovarian Neoplasms
Polymorphism, Single Nucleotide
Australian Cancer Study
Australian Ovarian Cancer Study
Consortium of Investigators of Modifiers of BRCA1/2
MD Multidisciplinary
Publication Status: Published
Article Number: 1627
Appears in Collections:Division of Surgery
Division of Cancer
Faculty of Medicine



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