Abstract
Epithelial ovarian cancer has a major heritable component, but the known susceptibility genes explain less than half the excess familial risk. 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, P trend = 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).
| Original language | English (US) |
|---|---|
| Pages (from-to) | 996-1000 |
| Number of pages | 5 |
| Journal | Nature Genetics |
| Volume | 41 |
| Issue number | 9 |
| DOIs | |
| State | Published - Sep 2009 |
ASJC Scopus subject areas
- Genetics
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A genome-wide association study identifies a new ovarian cancer susceptibility locus on 9p22.2. / Song, Honglin; Ramus, Susan J.; Tyrer, Jonathan; Bolton, Kelly L.; Gentry-Maharaj, Aleksandra; Wozniak, Eva; Anton-Culver, Hoda; Chang-Claude, Jenny; Cramer, Daniel W.; DiCioccio, Richard; Dörk, Thilo; Goode, Ellen L.; Goodman, Marc T.; Schildkraut, Joellen M.; Sellers, Thomas; Baglietto, Laura; Beckmann, Matthias W.; Beesley, Jonathan; Blaakaer, Jan; Carney, Michael E.; Chanock, Stephen; Chen, Zhihua; Cunningham, Julie M.; Dicks, Ed; Doherty, Jennifer A.; Dürst, Matthias; Ekici, Arif B.; Fenstermacher, David; Fridley, Brooke L.; Giles, Graham; Gore, Martin E.; De Vivo, Immaculata; Hillemanns, Peter; Hogdall, Claus; Hogdall, Estrid; Iversen, Edwin S.; Jacobs, Ian J.; Jakubowska, Anna; Li, Dong; Lissowska, Jolanta; Lubiński, Jan; Lurie, Galina; McGuire, Valerie; McLaughlin, John; Mȩdrek, Krzysztof; Moorman, Patricia G.; Moysich, Kirsten; Narod, Steven; Phelan, Catherine; Pye, Carole; Risch, Harvey; Runnebaum, Ingo B.; Severi, Gianluca; Southey, Melissa; Stram, Daniel O.; Thiel, Falk C.; Terry, Kathryn L.; Tsai, Ya Yu; Tworoger, Shelley S.; Van Den Berg, David J.; Vierkant, Robert A.; Wang-Gohrke, Shan; Webb, Penelope M.; Wilkens, Lynne R.; Wu, Anna H.; Yang, Hannah; Brewster, Wendy; Ziogas, Argyrios; Houlston, Richard; Tomlinson, Ian; Whittemore, Alice S.; Rossing, Mary Anne; Ponder, Bruce A.J.; Pearce, Celeste Leigh; Ness, Roberta B.; Menon, Usha; Kjaer, Susanne Krüger; Gronwald, Jacek; Garcia-Closas, Montserrat; Fasching, Peter A.; Easton, Douglas F.; Chenevix-Trench, Georgia; Berchuck, Andrew; Pharoah, Paul D.P.; Gayther, Simon A.
In: Nature Genetics, Vol. 41, No. 9, 09.2009, p. 996-1000.Research output: Contribution to journal › Article › peer-review
}
TY - JOUR
T1 - A genome-wide association study identifies a new ovarian cancer susceptibility locus on 9p22.2
AU - Song, Honglin
AU - Ramus, Susan J.
AU - Tyrer, Jonathan
AU - Bolton, Kelly L.
AU - Gentry-Maharaj, Aleksandra
AU - Wozniak, Eva
AU - Anton-Culver, Hoda
AU - Chang-Claude, Jenny
AU - Cramer, Daniel W.
AU - DiCioccio, Richard
AU - Dörk, Thilo
AU - Goode, Ellen L.
AU - Goodman, Marc T.
AU - Schildkraut, Joellen M.
AU - Sellers, Thomas
AU - Baglietto, Laura
AU - Beckmann, Matthias W.
AU - Beesley, Jonathan
AU - Blaakaer, Jan
AU - Carney, Michael E.
AU - Chanock, Stephen
AU - Chen, Zhihua
AU - Cunningham, Julie M.
AU - Dicks, Ed
AU - Doherty, Jennifer A.
AU - Dürst, Matthias
AU - Ekici, Arif B.
AU - Fenstermacher, David
AU - Fridley, Brooke L.
AU - Giles, Graham
AU - Gore, Martin E.
AU - De Vivo, Immaculata
AU - Hillemanns, Peter
AU - Hogdall, Claus
AU - Hogdall, Estrid
AU - Iversen, Edwin S.
AU - Jacobs, Ian J.
AU - Jakubowska, Anna
AU - Li, Dong
AU - Lissowska, Jolanta
AU - Lubiński, Jan
AU - Lurie, Galina
AU - McGuire, Valerie
AU - McLaughlin, John
AU - Mȩdrek, Krzysztof
AU - Moorman, Patricia G.
AU - Moysich, Kirsten
AU - Narod, Steven
AU - Phelan, Catherine
AU - Pye, Carole
AU - Risch, Harvey
AU - Runnebaum, Ingo B.
AU - Severi, Gianluca
AU - Southey, Melissa
AU - Stram, Daniel O.
AU - Thiel, Falk C.
AU - Terry, Kathryn L.
AU - Tsai, Ya Yu
AU - Tworoger, Shelley S.
AU - Van Den Berg, David J.
AU - Vierkant, Robert A.
AU - Wang-Gohrke, Shan
AU - Webb, Penelope M.
AU - Wilkens, Lynne R.
AU - Wu, Anna H.
AU - Yang, Hannah
AU - Brewster, Wendy
AU - Ziogas, Argyrios
AU - Houlston, Richard
AU - Tomlinson, Ian
AU - Whittemore, Alice S.
AU - Rossing, Mary Anne
AU - Ponder, Bruce A.J.
AU - Pearce, Celeste Leigh
AU - Ness, Roberta B.
AU - Menon, Usha
AU - Kjaer, Susanne Krüger
AU - Gronwald, Jacek
AU - Garcia-Closas, Montserrat
AU - Fasching, Peter A.
AU - Easton, Douglas F.
AU - Chenevix-Trench, Georgia
AU - Berchuck, Andrew
AU - Pharoah, Paul D.P.
AU - Gayther, Simon A.
N1 - Funding Information: We thank all the individuals who took part in this study. We thank all the researchers, clinicians and administrative staff who have enabled the many studies contributing to this work. In particular we thank A. Ryan and J. Ford (UKOPS); J. Morrison, the SEARCH team, U. Eilber and T. Koehler (GER); D. Bowtell, A. deFazio, D. Gertig, A. Green (AOCS); A. Green, P. Parsons, N. Hayward, D. Whiteman (ACS); L. Brinton, M. Sherman, A. Hutchinson, N. Szeszenia-Dabrowska, B. Peplonska, W. Zatonski, A. Soni, P. Chao, M. Stagner (POL1); N. Bogdanova, S. Haubold, P. Schürmann, F. Kramer, T.-W. Park-Simon, K. Beer-Grondke and D. Schmidt (HJOCS). The genotyping and data analysis for this study was supported by a project grant from Cancer Research UK. We acknowledge the computational resources provided by the University of Cambridge (CamGrid). The Ovarian Cancer Association Consortium is supported by a grant from the Ovarian Cancer Research Fund thanks to donations by the family and friends of Kathryn Sladek Smith. D.F.E. and P.D.P.P. are supported by Cancer Research UK, S.J.R. by the Mermaid/Eve Appeal, G.C.-T. and P.M.W. by the NHMRC, and P.A.F. by the Deutsche Krebshilfe e.V. Funding of the constituent studies was provided by the Roswell Park Alliance, the Danish Cancer Society and the US National Cancer Institute (CA71766, CA16056, R01 CA61107, R01 CA122443, R01 CA054419, P50 CA105009,R01CA114343, R01 CA87538, R01 CA112523, R01-CA-58598, N01-CN-55424 and N01-PC-35137, R01-CA-122443, CA-58860, CA-92044), the US Army Medical Research and Material Command (DAMD17-01-1-0729), the Cancer Council Tasmania and Cancer Foundation of Western Australia (AOCS study), the National Health and Medical Research Council of Australia (199600; ACS study), German Federal Ministry of Education and Research of Germany Programme of Clinical Biomedical Research (01 GB 9401), and the genotyping in part by the state of Baden-Württemberg through Medical Faculty of the University of Ulm (P.685; GER), the Mayo Foundation and the Lon V. Smith Foundation (grant LVS-39420). The UKOPS study is funded by the Oak Foundation. Some of this work was undertaken at University College Hospital, London which receives a proportion of its funding from the UK Department of Health’s National Institute for Health Research Biomedical Research Centre funding scheme.
PY - 2009/9
Y1 - 2009/9
N2 - Epithelial ovarian cancer has a major heritable component, but the known susceptibility genes explain less than half the excess familial risk. 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, P trend = 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).
AB - Epithelial ovarian cancer has a major heritable component, but the known susceptibility genes explain less than half the excess familial risk. 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, P trend = 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).
UR - http://www.scopus.com/inward/record.url?scp=69349102630&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=69349102630&partnerID=8YFLogxK
U2 - 10.1038/ng.424
DO - 10.1038/ng.424
M3 - Article
C2 - 19648919
AN - SCOPUS:69349102630
VL - 41
SP - 996
EP - 1000
JO - Nature Genetics
JF - Nature Genetics
SN - 1061-4036
IS - 9
ER -