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 CampbellAlice 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

Research output: Contribution to journalArticle

254 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 languageEnglish (US)
Pages (from-to)874-879
Number of pages6
JournalNature Genetics
Volume42
Issue number10
DOIs
StatePublished - Oct 2010

ASJC Scopus subject areas

  • Genetics

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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