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

Honglin Song; Susan J. Ramus; Jonathan Tyrer; Kelly L. Bolton; Aleksandra Gentry-Maharaj; Eva Wozniak; Hoda Anton-Culver; Jenny Chang-Claude; Daniel W. Cramer; Richard DiCioccio; Thilo Dörk; Ellen L. Goode; Marc T. Goodman; Joellen M. Schildkraut; Thomas Sellers; Laura Baglietto; Matthias W. Beckmann; Jonathan Beesley; Jan Blaakaer; Michael E. Carney; Stephen Chanock; Zhihua Chen; Julie M. Cunningham; Ed Dicks; Jennifer A. Doherty; Matthias Dürst; Arif B. Ekici; David Fenstermacher; Brooke L. Fridley; Graham Giles; Martin E. Gore; Immaculata De Vivo; Peter Hillemanns; Claus Hogdall; Estrid Hogdall; Edwin S. Iversen; Ian J. Jacobs; Anna Jakubowska; Dong Li; Jolanta Lissowska; Jan Lubiński; Galina Lurie; Valerie McGuire; John McLaughlin; Krzysztof Mȩdrek; Patricia G. Moorman; Kirsten Moysich; Steven Narod; Catherine Phelan; Carole Pye; Harvey Risch; Ingo B. Runnebaum; Gianluca Severi; Melissa Southey; Daniel O. Stram; Falk C. Thiel; Kathryn L. Terry; Ya Yu Tsai; Shelley S. Tworoger; David J. Van Den Berg; Robert A. Vierkant; Shan Wang-Gohrke; Penelope M. Webb; Lynne R. Wilkens; Anna H. Wu; Hannah Yang; Wendy Brewster; Argyrios Ziogas; Richard Houlston; Ian Tomlinson; Alice S. Whittemore; Mary Anne Rossing; Bruce A.J. Ponder; Celeste Leigh Pearce; Roberta B. Ness; Usha Menon; Susanne Krüger Kjaer; Jacek Gronwald; Montserrat Garcia-Closas; Peter A. Fasching; Douglas F. Easton; Georgia Chenevix-Trench; Andrew Berchuck; Paul D.P. Pharoah; Simon A. Gayther

doi:10.1038/ng.424

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

Honglin Song, Susan J. Ramus, Jonathan Tyrer, Kelly L. Bolton, Aleksandra Gentry-Maharaj, Eva Wozniak, Hoda Anton-Culver, Jenny Chang-Claude, Daniel W. Cramer, Richard DiCioccio, Thilo Dörk, Ellen L. Goode, Marc T. Goodman, Joellen M. Schildkraut, Thomas Sellers, Laura Baglietto, Matthias W. Beckmann, Jonathan Beesley, Jan Blaakaer, Michael E. CarneyStephen Chanock, Zhihua Chen, Julie M. Cunningham, Ed Dicks, Jennifer A. Doherty, Matthias Dürst, Arif B. Ekici, David Fenstermacher, Brooke L. Fridley, Graham Giles, Martin E. Gore, Immaculata De Vivo, Peter Hillemanns, Claus Hogdall, Estrid Hogdall, Edwin S. Iversen, Ian J. Jacobs, Anna Jakubowska, Dong Li, Jolanta Lissowska, Jan Lubiński, Galina Lurie, Valerie McGuire, John McLaughlin, Krzysztof Mȩdrek, Patricia G. Moorman, Kirsten Moysich, Steven Narod, Catherine Phelan, Carole Pye, Harvey Risch, Ingo B. Runnebaum, Gianluca Severi, Melissa Southey, Daniel O. Stram, Falk C. Thiel, Kathryn L. Terry, Ya Yu Tsai, Shelley S. Tworoger, David J. Van Den Berg, Robert A. Vierkant, Shan Wang-Gohrke, Penelope M. Webb, Lynne R. Wilkens, Anna H. Wu, Hannah Yang, Wendy Brewster, Argyrios Ziogas, Richard Houlston, Ian Tomlinson, Alice S. Whittemore, Mary Anne Rossing, Bruce A.J. Ponder, Celeste Leigh Pearce, Roberta B. Ness, Usha Menon, Susanne Krüger Kjaer, Jacek Gronwald, Montserrat Garcia-Closas, Peter A. Fasching, Douglas F. Easton, Georgia Chenevix-Trench, Andrew Berchuck, Paul D.P. Pharoah, Simon A. Gayther

Research output: Contribution to journal › Article › peer-review

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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, P_trend = 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	https://doi.org/10.1038/ng.424
State	Published - Sep 2009
Externally published	Yes

ASJC Scopus subject areas

Genetics

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Song, H., Ramus, S. J., Tyrer, J., Bolton, K. L., Gentry-Maharaj, A., Wozniak, E., Anton-Culver, H., Chang-Claude, J., Cramer, D. W., DiCioccio, R., Dörk, T., Goode, E. L., Goodman, M. T., Schildkraut, J. M., Sellers, T., Baglietto, L., Beckmann, M. W., Beesley, J., Blaakaer, J., ... Gayther, S. A. (2009). A genome-wide association study identifies a new ovarian cancer susceptibility locus on 9p22.2. Nature genetics, 41(9), 996-1000. https://doi.org/10.1038/ng.424

Song, H, Ramus, SJ, Tyrer, J, Bolton, KL, Gentry-Maharaj, A, Wozniak, E, Anton-Culver, H, Chang-Claude, J, Cramer, DW, DiCioccio, R, Dörk, T, Goode, EL, Goodman, MT, Schildkraut, JM, Sellers, T, Baglietto, L, Beckmann, MW, Beesley, J, Blaakaer, J, Carney, ME, Chanock, S, Chen, Z, Cunningham, JM, Dicks, E, Doherty, JA, Dürst, M, Ekici, AB, Fenstermacher, D, Fridley, BL, Giles, G, Gore, ME, De Vivo, I, Hillemanns, P, Hogdall, C, Hogdall, E, Iversen, ES, Jacobs, IJ, Jakubowska, A, Li, D, Lissowska, J, Lubiński, J, Lurie, G, McGuire, V, McLaughlin, J, Mȩdrek, K, Moorman, PG, Moysich, K, Narod, S, Phelan, C, Pye, C, Risch, H, Runnebaum, IB, Severi, G, Southey, M, Stram, DO, Thiel, FC, Terry, KL, Tsai, YY, Tworoger, SS, Van Den Berg, DJ, Vierkant, RA, Wang-Gohrke, S, Webb, PM, Wilkens, LR, Wu, AH, Yang, H, Brewster, W, Ziogas, A, Houlston, R, Tomlinson, I, Whittemore, AS, Rossing, MA, Ponder, BAJ, Pearce, CL, Ness, RB, Menon, U, Kjaer, SK, Gronwald, J, Garcia-Closas, M, Fasching, PA, Easton, DF, Chenevix-Trench, G, Berchuck, A, Pharoah, PDP & Gayther, SA 2009, 'A genome-wide association study identifies a new ovarian cancer susceptibility locus on 9p22.2', Nature genetics, vol. 41, no. 9, pp. 996-1000. https://doi.org/10.1038/ng.424

@article{77510b85c9f447bc91c2dc17a934c76b,

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

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).",

author = "Honglin Song and Ramus, {Susan J.} and Jonathan Tyrer and Bolton, {Kelly L.} and Aleksandra Gentry-Maharaj and Eva Wozniak and Hoda Anton-Culver and Jenny Chang-Claude and Cramer, {Daniel W.} and Richard DiCioccio and Thilo D{\"o}rk and Goode, {Ellen L.} and Goodman, {Marc T.} and Schildkraut, {Joellen M.} and Thomas Sellers and Laura Baglietto and Beckmann, {Matthias W.} and Jonathan Beesley and Jan Blaakaer and Carney, {Michael E.} and Stephen Chanock and Zhihua Chen and Cunningham, {Julie M.} and Ed Dicks and Doherty, {Jennifer A.} and Matthias D{\"u}rst and Ekici, {Arif B.} and David Fenstermacher and Fridley, {Brooke L.} and Graham Giles and Gore, {Martin E.} and {De Vivo}, Immaculata and Peter Hillemanns and Claus Hogdall and Estrid Hogdall and Iversen, {Edwin S.} and Jacobs, {Ian J.} and Anna Jakubowska and Dong Li and Jolanta Lissowska and Jan Lubi{\'n}ski and Galina Lurie and Valerie McGuire and John McLaughlin and Krzysztof Mȩdrek and Moorman, {Patricia G.} and Kirsten Moysich and Steven Narod and Catherine Phelan and Carole Pye and Harvey Risch and Runnebaum, {Ingo B.} and Gianluca Severi and Melissa Southey and Stram, {Daniel O.} and Thiel, {Falk C.} and Terry, {Kathryn L.} and Tsai, {Ya Yu} and Tworoger, {Shelley S.} and {Van Den Berg}, {David J.} and Vierkant, {Robert A.} and Shan Wang-Gohrke and Webb, {Penelope M.} and Wilkens, {Lynne R.} and Wu, {Anna H.} and Hannah Yang and Wendy Brewster and Argyrios Ziogas and Richard Houlston and Ian Tomlinson and Whittemore, {Alice S.} and Rossing, {Mary Anne} and Ponder, {Bruce A.J.} and Pearce, {Celeste Leigh} and Ness, {Roberta B.} and Usha Menon and Kjaer, {Susanne Kr{\"u}ger} and Jacek Gronwald and Montserrat Garcia-Closas and Fasching, {Peter A.} and Easton, {Douglas F.} and Georgia Chenevix-Trench and Andrew Berchuck and Pharoah, {Paul D.P.} and Gayther, {Simon A.}",

note = "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. Sch{\"u}rmann, 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-W{\"u}rttemberg 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{\textquoteright}s National Institute for Health Research Biomedical Research Centre funding scheme.",

year = "2009",

month = sep,

doi = "10.1038/ng.424",

language = "English (US)",

volume = "41",

pages = "996--1000",

journal = "Nature genetics",

issn = "1061-4036",

publisher = "Nature Publishing Group",

number = "9",

}

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).

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U2 - 10.1038/ng.424

DO - 10.1038/ng.424

M3 - Article

C2 - 19648919

AN - SCOPUS:69349102630

SN - 1061-4036

VL - 41

SP - 996

EP - 1000

JO - Nature genetics

JF - Nature genetics

IS - 9

ER -

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

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