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A genome-wide association study identifies susceptibility loci for ovarian cancer at 2q31 and 8q24

A genome-wide association study identifies susceptibility loci for ovarian cancer at 2q31 and 8q24
A genome-wide association study identifies susceptibility loci for ovarian cancer at 2q31 and 8q24
Ovarian cancer accounts for more deaths than all other gynecological cancers combined. To identify common low-penetrance ovarian cancer susceptibility genes, we conducted a genome-wide association study of 507,094 SNPs in 1,768 individuals with ovarian cancer (cases) and 2,354 controls, with follow up of 21,955 SNPs in 4,162 cases and 4,810 controls, leading to the identification of a confirmed susceptibility locus at 9p22 (in BNC2). Here, we report on nine additional candidate loci (defined as having P ? 10??) identified after stratifying cases by histology, which we genotyped in an additional 4,353 cases and 6,021 controls. We confirmed two new susceptibility loci with P ? 5 × 10?? (8q24, P = 8.0 × 10?¹? and 2q31, P = 3.8 × 10?¹?) and identified two additional loci that approached genome-wide significance (3q25, P = 7.1 × 10?? and 17q21, P = 1.4 × 10??). The associations of these loci with serous ovarian cancer were generally stronger than with other cancer subtypes. Analysis of HOXD1, MYC, TIPARP and SKAP1 at these loci and of BNC2 at 9p22 supports a functional role for these genes in ovarian cancer development.
cancer genomics, genome-wide association studies, ovarian cancer
1061-4036
874-879
Goode, Ellen L
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Chenevix-Trench, Georgia
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Song, Honglin
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Ramus, Susan J
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Notaridou, Maria
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Lawrenson, Kate
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Widschwendter, Martin
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Larson, Melissa C
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Tomlinson, Ian
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Pharoah, Paul D P
c8fe0784-f4ab-4bf0-bd99-787a205a58cb

Goode, Ellen L, Chenevix-Trench, Georgia and Song, Honglin et al. (2010) A genome-wide association study identifies susceptibility loci for ovarian cancer at 2q31 and 8q24. Nature Genetics, 42 (10), 874-879. (doi:10.1038/ng.668). (PMID:20852632)

Record type: Article

Abstract

Ovarian cancer accounts for more deaths than all other gynecological cancers combined. To identify common low-penetrance ovarian cancer susceptibility genes, we conducted a genome-wide association study of 507,094 SNPs in 1,768 individuals with ovarian cancer (cases) and 2,354 controls, with follow up of 21,955 SNPs in 4,162 cases and 4,810 controls, leading to the identification of a confirmed susceptibility locus at 9p22 (in BNC2). Here, we report on nine additional candidate loci (defined as having P ? 10??) identified after stratifying cases by histology, which we genotyped in an additional 4,353 cases and 6,021 controls. We confirmed two new susceptibility loci with P ? 5 × 10?? (8q24, P = 8.0 × 10?¹? and 2q31, P = 3.8 × 10?¹?) and identified two additional loci that approached genome-wide significance (3q25, P = 7.1 × 10?? and 17q21, P = 1.4 × 10??). The associations of these loci with serous ovarian cancer were generally stronger than with other cancer subtypes. Analysis of HOXD1, MYC, TIPARP and SKAP1 at these loci and of BNC2 at 9p22 supports a functional role for these genes in ovarian cancer development.

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Accepted/In Press date: 27 July 2010
e-pub ahead of print date: 19 September 2010
Published date: October 2010
Keywords: cancer genomics, genome-wide association studies, ovarian cancer
Organisations: Cancer Sciences

Identifiers

Local EPrints ID: 384859
URI: http://eprints.soton.ac.uk/id/eprint/384859
DOI: doi:10.1038/ng.668
ISSN: 1061-4036
PURE UUID: b4def717-43c1-4f9f-ba26-d6213c769855
ORCID for Diana Eccles: ORCID iD orcid.org/0000-0002-9935-3169

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Date deposited: 07 Dec 2015 15:05
Last modified: 15 Mar 2024 02:40

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Contributors

Author: Ellen L Goode
Author: Georgia Chenevix-Trench
Author: Honglin Song
Author: Susan J Ramus
Author: Maria Notaridou
Author: Kate Lawrenson
Author: Martin Widschwendter
Author: Robert A Vierkant
Author: Melissa C Larson
Author: Susanne K Kjaer
Author: Michael J Birrer
Author: Andrew Berchuck
Author: Joellen Schildkraut
Author: Ian Tomlinson
Author: Lambertus A Kiemeney
Author: Linda S Cook
Author: Jacek Gronwald
Author: Montserrat Garcia-Closas
Author: Martin E Gore
Author: Ian Campbell
Author: Alice S Whittemore
Author: Rebecca Sutphen
Author: Catherine Phelan
Author: Hoda Anton-Culver
Author: Celeste Leigh Pearce
Author: Diether Lambrechts
Author: Mary Anne Rossing
Author: Jenny Chang-Claude
Author: Kirsten B Moysich
Author: Marc T Goodman
Author: Thilo Dörk
Author: Heli Nevanlinna
Author: Roberta B Ness
Author: Thorunn Rafnar
Author: Claus Hogdall
Author: Estrid Hogdall
Author: Brooke L Fridley
Author: Julie M Cunningham
Author: Weiva Sieh
Author: Valerie McGuire
Author: Andrew K Godwin
Author: Daniel W Cramer
Author: Dena Hernandez
Author: Douglas Levine
Author: Karen Lu
Author: Edwin S Iversen
Author: Rachel T Palmieri
Author: Richard Houlston
Author: Anne M van Altena
Author: Katja K H Aben
Author: Leon F A G Massuger
Author: Angela Brooks-Wilson
Author: Linda E Kelemen
Author: Nhu D Le
Author: Anna Jakubowska
Author: Jan Lubinski
Author: Krzysztof Medrek
Author: Anne Stafford
Author: Douglas F Easton
Author: Jonathan Tyrer
Author: Kelly L Bolton
Author: Patricia Harrington
Author: Diana Eccles ORCID iD
Author: Ann Chen
Author: Ashley N Molina
Author: Barbara N Davila
Author: Hector Arango
Author: Ya-Yu Tsai
Author: Zhihua Chen
Author: Harvey A Risch
Author: John McLaughlin
Author: Steven A Narod
Author: Argyrios Ziogas
Author: Wendy Brewster
Author: Aleksandra Gentry-Maharaj
Author: Usha Menon
Author: Anna H Wu
Author: Daniel O Stram
Author: Malcolm C Pike
Author: Jonathan Beesley
Author: Penelope M Webb
Author: Xiaoqing Chen
Author: Arif B Ekici
Author: Falk C Thiel
Author: Matthias W Beckmann
Author: Hannah Yang
Author: Nicolas Wentzensen
Author: Jolanta Lissowska
Author: Peter A Fasching
Author: Evelyn Despierre
Author: Frederic Amant
Author: Ignace Vergote
Author: Jennifer Doherty
Author: Rebecca Hein
Author: Shan Wang-Gohrke
Author: Galina Lurie
Author: Michael E Carney
Author: Pamela J Thompson
Author: Ingo Runnebaum
Author: Peter Hillemanns
Author: Matthias Dürst
Author: Natalia Antonenkova
Author: Natalia Bogdanova
Author: Arto Leminen
Author: Ralf Butzow
Author: Tuomas Heikkinen
Author: Kari Stefansson
Author: Patrick Sulem
Author: Sören Besenbacher
Author: Thomas A Sellers
Author: Simon A Gayther
Author: Paul D P Pharoah

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