A genome-wide association study identifies a new ovarian cancer susceptibility locus on 9p22.2

Chenevix-Trench, Georgia (2009) A genome-wide association study identifies a new ovarian cancer susceptibility locus on 9p22.2. Nature Genetics, 41 9: 996-1000. doi:10.1038/ng.424


Author Chenevix-Trench, Georgia
Title A genome-wide association study identifies a new ovarian cancer susceptibility locus on 9p22.2
Formatted title
A genome-wide association study identifies a new ovarian cancer susceptibility locus on 9p22.2
Journal name Nature Genetics   Check publisher's open access policy
ISSN 1061-4036
Publication date 2009-08-02
Sub-type Letter to editor, brief commentary or brief communication
DOI 10.1038/ng.424
Volume 41
Issue 9
Start page 996
End page 1000
Total pages 5
Editor Myles Axton
Place of publication United States
Publisher Nature Publishing Group
Language eng
Subject 111203 Cancer Genetics
9201 Clinical Health (Organs, Diseases and Abnormal Conditions)
CX
Abstract Epithelial ovarian cancer has a major heritable component, but the known susceptibility genes explain less than half the excess familial risk1. We performed a genome-wide association study (GWAS) to identify common ovarian cancer susceptibility alleles. We evaluated 507,094 SNPs genotyped in 1,817 cases and 2,353 controls from the UK and 2 million imputed SNPs. We genotyped the 22,790 top ranked SNPs in 4,274 cases and 4,809 controls of European ancestry from Europe, USA and Australia. We identified 12 SNPs at 9p22 associated with disease risk (P < 10-8). The most significant SNP (rs3814113; P = 2.5 10-17) was genotyped in a further 2,670 ovarian cancer cases and 4,668 controls, confirming its association (combined data odds ratio (OR) = 0.82, 95% confidence interval (CI) 0.79–0.86, Ptrend = 5.1 10-19). The association differs by histological subtype, being strongest for serous ovarian cancers (OR 0.77, 95% CI 0.73–0.81, Ptrend = 4.1 10-21). Honglin Song1,43, Susan J Ramus2,43, Jonathan Tyrer1, Kelly L Bolton1,3, Aleksandra Gentry-Maharaj2, Eva Wozniak2, Hoda Anton-Culver4, Jenny Chang-Claude5, Daniel W Cramer6, Richard DiCioccio7, Thilo Dörk8, Ellen L Goode9, Marc T Goodman10, Joellen M Schildkraut11, Thomas Sellers12, Laura Baglietto13,14, Matthias W Beckmann15, Jonathan Beesley16, Jan Blaakaer17, Michael E Carney10, Stephen Chanock3, Zhihua Chen12, Julie M Cunningham9, Ed Dicks1, Jennifer A Doherty18, Matthias Dürst19, Arif B Ekici20, David Fenstermacher12, Brooke L Fridley9, Graham Giles13,14, Martin E Gore21, Immaculata De Vivo22, Peter Hillemanns8, Claus Hogdall23, Estrid Hogdall24, Edwin S Iversen25, Ian J Jacobs2, Anna Jakubowska26, Dong Li4, Jolanta Lissowska27, Jan Lubiski26, Galina Lurie10, Valerie McGuire28, John McLaughlin29, Krzysztof Mdrek26, Patricia G Moorman11, Kirsten Moysich30, Steven Narod31, Catherine Phelan12, Carole Pye1, Harvey Risch32, Ingo B Runnebaum19, Gianluca Severi13,14, Melissa Southey33, Daniel O Stram34, Falk C Thiel15, Kathryn L Terry6, Ya-Yu Tsai12, Shelley S Tworoger22, David J Van Den Berg34, Robert A Vierkant9, Shan Wang-Gohrke35, Penelope M Webb16, Lynne R Wilkens10, Anna H Wu34, Hannah Yang3, Wendy Brewster36, Argyrios Ziogas4, Australian Cancer (Ovarian) Study37, The Australian Ovarian Cancer Study Group37, The Ovarian Cancer Association Consortium38, Richard Houlston38, Ian Tomlinson39, Alice S Whittemore28, Mary Anne Rossing18, Bruce A J Ponder1, Celeste Leigh Pearce34, Roberta B Ness40, Usha Menon2, Susanne Krüger Kjaer24, Jacek Gronwald26, Montserrat Garcia-Closas17, Peter A Fasching15,41, Douglas F Easton42, Georgia Chenevix-Trench16, Andrew Berchuck11, Paul D P Pharoah1 & Simon A Gayther2
Formatted abstract
Epithelial ovarian cancer has a major heritable component, but the known susceptibility genes explain less than half the excess familial risk1. We performed a genome-wide association study (GWAS) to identify common ovarian cancer susceptibility alleles. We evaluated 507,094 SNPs genotyped in 1,817 cases and 2,353 controls from the UK and 2 million imputed SNPs. We genotyped the 22,790 top ranked SNPs in 4,274 cases and 4,809 controls of European ancestry from Europe, USA and Australia. We identified 12 SNPs at 9p22 associated with disease risk (P < 10-8). The most significant SNP (rs3814113; P = 2.5 10-17) was genotyped in a further 2,670 ovarian cancer cases and 4,668 controls, confirming its association (combined data odds ratio (OR) = 0.82, 95% confidence interval (CI) 0.79–0.86, Ptrend = 5.1 10-19). The association differs by histological subtype, being strongest for serous ovarian cancers (OR 0.77, 95% CI 0.73–0.81, Ptrend = 4.1 10-21).

Honglin Song1,43, Susan J Ramus2,43, Jonathan Tyrer1, Kelly L Bolton1,3, Aleksandra Gentry-Maharaj2, Eva Wozniak2, Hoda Anton-Culver4, Jenny Chang-Claude5, Daniel W Cramer6, Richard DiCioccio7, Thilo Dörk8, Ellen L Goode9, Marc T Goodman10, Joellen M Schildkraut11, Thomas Sellers12, Laura Baglietto13,14, Matthias W Beckmann15, Jonathan Beesley16, Jan Blaakaer17, Michael E Carney10, Stephen Chanock3, Zhihua Chen12, Julie M Cunningham9, Ed Dicks1, Jennifer A Doherty18, Matthias Dürst19, Arif B Ekici20, David Fenstermacher12, Brooke L Fridley9, Graham Giles13,14, Martin E Gore21, Immaculata De Vivo22, Peter Hillemanns8, Claus Hogdall23, Estrid Hogdall24, Edwin S Iversen25, Ian J Jacobs2, Anna Jakubowska26, Dong Li4, Jolanta Lissowska27, Jan Lubiski26, Galina Lurie10, Valerie McGuire28, John McLaughlin29, Krzysztof Mdrek26, Patricia G Moorman11, Kirsten Moysich30, Steven Narod31, Catherine Phelan12, Carole Pye1, Harvey Risch32, Ingo B Runnebaum19, Gianluca Severi13,14, Melissa Southey33, Daniel O Stram34, Falk C Thiel15, Kathryn L Terry6, Ya-Yu Tsai12, Shelley S Tworoger22, David J Van Den Berg34, Robert A Vierkant9, Shan Wang-Gohrke35, Penelope M Webb16, Lynne R Wilkens10, Anna H Wu34, Hannah Yang3, Wendy Brewster36, Argyrios Ziogas4, Australian Cancer (Ovarian) Study37, The Australian Ovarian Cancer Study Group37, The Ovarian Cancer Association Consortium38, Richard Houlston38, Ian Tomlinson39, Alice S Whittemore28, Mary Anne Rossing18, Bruce A J Ponder1, Celeste Leigh Pearce34, Roberta B Ness40, Usha Menon2, Susanne Krüger Kjaer24, Jacek Gronwald26, Montserrat Garcia-Closas17, Peter A Fasching15,41, Douglas F Easton42, Georgia Chenevix-Trench16, Andrew Berchuck11, Paul D P Pharoah1 & Simon A Gayther2


Q-Index Code CX
Additional Notes complete author list entered after abstract

Document type: Journal Article
Sub-type: Letter to editor, brief commentary or brief communication
Collection: School of Medicine Publications
 
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Created: Wed, 31 Mar 2010, 12:52:24 EST by Amanda Jones on behalf of Medicine - Royal Brisbane and Women's Hospital