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

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

doi:10.1038/ng.668

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

Ellen L. Goode
, Georgia Chenevix-Trench
, Honglin Song
, Susan J. Ramus
, Maria Notaridou
, Kate Lawrenson
, Martin Widschwendter
, Robert A. Vierkant
, Melissa C. Larson
, Susanne K. Kjaer
, Michael J. Birrer
, Andrew Berchuck
, Joellen Schildkraut
, Ian Tomlinson
, Lambertus A. Kiemeney
, Linda S. Cook
, Jacek Gronwald
, Montserrat Garcia-Closas
, Martin E. Gore
, Ian Campbell

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

Department of Epidemiology and Environmental Health

Mayo Clinic Rochester, MN
Post Office Royal Brisbane Hospital
University of Cambridge
University College London
University of Copenhagen
Danish Cancer Society
Massachusetts General Hospital
Duke University
Queen Mary University of London
Radboud University Nijmegen
University of New Mexico
Alberta Health Services
Pomeranian Medical University in Szczecin
National Institutes of Health
Royal Marsden NHS Foundation Trust
Peter Maccallum Cancer Centre
University of Melbourne
Stanford University
University of South Florida
Moffitt Cancer Center
University of California at Irvine
University of Southern California
Flanders Institute for Biotechnology
Fred Hutchinson Cancer Research Center
German Cancer Research Center
University of Hawai'i at Mānoa
Hannover Medical School
Helsinki University Hospital
University of Texas Health Science Center at Houston
deCODE genetics
Fox Chase Cancer Center
Brigham and Women’s Hospital
Memorial Sloan-Kettering Cancer Center
University of Texas MD Anderson Cancer Center
University of North Carolina at Chapel Hill
The Institute of Cancer Research
Netherlands Association of Comprehensive Cancer Centres
Provincial Health Services Authority
Simon Fraser University
University of Southampton
Yale University
Cancer Care Ontario
West Coast Gynecologic Oncology
University of Toronto
Friedrich-Alexander University Erlangen-Nürnberg
Maria Sklodowska-Curie Institute of Oncology
University of California at Los Angeles
KU Leuven
Ulm University
Friedrich Schiller University Jena
Byelorussian Institute for Oncology and Medical Radiology Aleksandrov N.N.

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

313 Scopus citations

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 -4) 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 -8 (8q24, P = 8.0 × 10 -15 and 2q31, P = 3.8 × 10 -14) and identified two additional loci that approached genome-wide significance (3q25, P = 7.1 × 10 -8 and 17q21, P = 1.4 × 10 -7). 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.

Original language	English
Pages (from-to)	874-879
Number of pages	6
Journal	Nature Genetics
Volume	42
Issue number	10
DOIs	https://doi.org/10.1038/ng.668
State	Published - Oct 2010

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10.1038/ng.668

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Goode, E. L., Chenevix-Trench, G., Song, H., Ramus, S. J., Notaridou, M., Lawrenson, K., Widschwendter, M., Vierkant, R. A., Larson, M. C., Kjaer, S. K., Birrer, M. J., Berchuck, A., Schildkraut, J., Tomlinson, I., Kiemeney, L. A., Cook, L. S., Gronwald, J., Garcia-Closas, M., Gore, M. E., ... Pharoah, P. D. P. (2010). A genome-wide association study identifies susceptibility loci for ovarian cancer at 2q31 and 8q24. Nature Genetics, 42(10), 874-879. https://doi.org/10.1038/ng.668

@article{a2f1dfe26d8e494c91b6e388009c12cf,

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

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 -4) 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 -8 (8q24, P = 8.0 × 10 -15 and 2q31, P = 3.8 × 10 -14) and identified two additional loci that approached genome-wide significance (3q25, P = 7.1 × 10 -8 and 17q21, P = 1.4 × 10 -7). 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.",

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

year = "2010",

month = oct,

doi = "10.1038/ng.668",

language = "English",

volume = "42",

pages = "874--879",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Research",

number = "10",

}

Goode, EL, Chenevix-Trench, G, Song, H, Ramus, SJ, Notaridou, M, Lawrenson, K, Widschwendter, M, Vierkant, RA, Larson, MC, Kjaer, SK, Birrer, MJ, Berchuck, A, Schildkraut, J, Tomlinson, I, Kiemeney, LA, Cook, LS, Gronwald, J, Garcia-Closas, M, Gore, ME, Campbell, I, Whittemore, AS, Sutphen, R, Phelan, C, Anton-Culver, H, Pearce, CL, Lambrechts, D, Rossing, MA, Chang-Claude, J, Moysich, KB, Goodman, MT, Dörk, T, Nevanlinna, H, Ness, RB, Rafnar, T, Hogdall, C, Hogdall, E, Fridley, BL, Cunningham, JM, Sieh, W, McGuire, V, Godwin, AK, Cramer, DW, Hernandez, D, Levine, D, Lu, K, Iversen, ES, Palmieri, RT, Houlston, R, Van Altena, AM, Aben, KKH, Massuger, LFAG, Brooks-Wilson, A, Kelemen, LE, Le, ND, Jakubowska, A, Lubinski, J, Medrek, K, Stafford, A, Easton, DF, Tyrer, J, Bolton, KL, Harrington, P, Eccles, D, Chen, A, Molina, AN, Davila, BN, Arango, H, Tsai, YY, Chen, Z, Risch, HA, McLaughlin, J, Narod, SA, Ziogas, A, Brewster, W, Gentry-Maharaj, A, Menon, U, Wu, AH, Stram, DO, Pike, MC, Beesley, J, Webb, PM, Chen, X, Ekici, AB, Thiel, FC, Beckmann, MW, Yang, H, Wentzensen, N, Lissowska, J, Fasching, PA, Despierre, E, Amant, F, Vergote, I, Doherty, J, Hein, R, Wang-Gohrke, S, Lurie, G, Carney, ME, Thompson, PJ, Runnebaum, I, Hillemanns, P, Dürst, M, Antonenkova, N, Bogdanova, N, Leminen, A, Butzow, R, Heikkinen, T, Stefansson, K, Sulem, P, Besenbacher, S, Sellers, TA, Gayther, SA & Pharoah, PDP 2010, 'A genome-wide association study identifies susceptibility loci for ovarian cancer at 2q31 and 8q24', Nature Genetics, vol. 42, no. 10, pp. 874-879. https://doi.org/10.1038/ng.668

TY - JOUR

T1 - A genome-wide association study identifies susceptibility loci for ovarian cancer at 2q31 and 8q24

AU - Goode, Ellen L.

AU - Chenevix-Trench, Georgia

AU - Song, Honglin

AU - Ramus, Susan J.

AU - Notaridou, Maria

AU - Lawrenson, Kate

AU - Widschwendter, Martin

AU - Vierkant, Robert A.

AU - Larson, Melissa C.

AU - Kjaer, Susanne K.

AU - Birrer, Michael J.

AU - Berchuck, Andrew

AU - Schildkraut, Joellen

AU - Tomlinson, Ian

AU - Kiemeney, Lambertus A.

AU - Cook, Linda S.

AU - Gronwald, Jacek

AU - Garcia-Closas, Montserrat

AU - Gore, Martin E.

AU - Campbell, Ian

AU - Whittemore, Alice S.

AU - Sutphen, Rebecca

AU - Phelan, Catherine

AU - Anton-Culver, Hoda

AU - Pearce, Celeste Leigh

AU - Lambrechts, Diether

AU - Rossing, Mary Anne

AU - Chang-Claude, Jenny

AU - Moysich, Kirsten B.

AU - Goodman, Marc T.

AU - Dörk, Thilo

AU - Nevanlinna, Heli

AU - Ness, Roberta B.

AU - Rafnar, Thorunn

AU - Hogdall, Claus

AU - Hogdall, Estrid

AU - Fridley, Brooke L.

AU - Cunningham, Julie M.

AU - Sieh, Weiva

AU - McGuire, Valerie

AU - Godwin, Andrew K.

AU - Cramer, Daniel W.

AU - Hernandez, Dena

AU - Levine, Douglas

AU - Lu, Karen

AU - Iversen, Edwin S.

AU - Palmieri, Rachel T.

AU - Houlston, Richard

AU - Van Altena, Anne M.

AU - Aben, Katja K.H.

AU - Massuger, Leon F.A.G.

AU - Brooks-Wilson, Angela

AU - Kelemen, Linda E.

AU - Le, Nhu D.

AU - Jakubowska, Anna

AU - Lubinski, Jan

AU - Medrek, Krzysztof

AU - Stafford, Anne

AU - Easton, Douglas F.

AU - Tyrer, Jonathan

AU - Bolton, Kelly L.

AU - Harrington, Patricia

AU - Eccles, Diana

AU - Chen, Ann

AU - Molina, Ashley N.

AU - Davila, Barbara N.

AU - Arango, Hector

AU - Tsai, Ya Yu

AU - Chen, Zhihua

AU - Risch, Harvey A.

AU - McLaughlin, John

AU - Narod, Steven A.

AU - Ziogas, Argyrios

AU - Brewster, Wendy

AU - Gentry-Maharaj, Aleksandra

AU - Menon, Usha

AU - Wu, Anna H.

AU - Stram, Daniel O.

AU - Pike, Malcolm C.

AU - Beesley, Jonathan

AU - Webb, Penelope M.

AU - Chen, Xiaoqing

AU - Ekici, Arif B.

AU - Thiel, Falk C.

AU - Beckmann, Matthias W.

AU - Yang, Hannah

AU - Wentzensen, Nicolas

AU - Lissowska, Jolanta

AU - Fasching, Peter A.

AU - Despierre, Evelyn

AU - Amant, Frederic

AU - Vergote, Ignace

AU - Doherty, Jennifer

AU - Hein, Rebecca

AU - Wang-Gohrke, Shan

AU - Lurie, Galina

AU - Carney, Michael E.

AU - Thompson, Pamela J.

AU - Runnebaum, Ingo

AU - Hillemanns, Peter

AU - Dürst, Matthias

AU - Antonenkova, Natalia

AU - Bogdanova, Natalia

AU - Leminen, Arto

AU - Butzow, Ralf

AU - Heikkinen, Tuomas

AU - Stefansson, Kari

AU - Sulem, Patrick

AU - Besenbacher, Sören

AU - Sellers, Thomas A.

AU - Gayther, Simon A.

AU - Pharoah, Paul D.P.

PY - 2010/10

Y1 - 2010/10

N2 - 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 -4) 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 -8 (8q24, P = 8.0 × 10 -15 and 2q31, P = 3.8 × 10 -14) and identified two additional loci that approached genome-wide significance (3q25, P = 7.1 × 10 -8 and 17q21, P = 1.4 × 10 -7). 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.

AB - 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 -4) 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 -8 (8q24, P = 8.0 × 10 -15 and 2q31, P = 3.8 × 10 -14) and identified two additional loci that approached genome-wide significance (3q25, P = 7.1 × 10 -8 and 17q21, P = 1.4 × 10 -7). 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.

UR - https://www.scopus.com/pages/publications/77957571905

U2 - 10.1038/ng.668

DO - 10.1038/ng.668

M3 - Article

C2 - 20852632

AN - SCOPUS:77957571905

SN - 1061-4036

VL - 42

SP - 874

EP - 879

JO - Nature Genetics

JF - Nature Genetics

IS - 10

ER -

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

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