Article | Published:

GWAS meta-analysis and replication identifies three new susceptibility loci for ovarian cancer

Nature Genetics volume 45, pages 362370 (2013) | Download Citation

Abstract

Genome-wide association studies (GWAS) have identified four susceptibility loci for epithelial ovarian cancer (EOC), with another two suggestive loci reaching near genome-wide significance. We pooled data from a GWAS conducted in North America with another GWAS from the UK. We selected the top 24,551 SNPs for inclusion on the iCOGS custom genotyping array. We performed follow-up genotyping in 18,174 individuals with EOC (cases) and 26,134 controls from 43 studies from the Ovarian Cancer Association Consortium. We validated the two loci at 3q25 and 17q21 that were previously found to have associations close to genome-wide significance and identified three loci newly associated with risk: two loci associated with all EOC subtypes at 8q21 (rs11782652, P = 5.5 × 10−9) and 10p12 (rs1243180, P = 1.8 × 10−8) and another locus specific to the serous subtype at 17q12 (rs757210, P = 8.1 × 10−10). An integrated molecular analysis of genes and regulatory regions at these loci provided evidence for functional mechanisms underlying susceptibility and implicated CHMP4C in the pathogenesis of ovarian cancer.

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References

  1. 1.

    et al. Environmental and heritable factors in the causation of cancer—analyses of cohorts of twins from Sweden, Denmark and Finland. N. Engl. J. Med. 343, 78–85 (2000).

  2. 2.

    , , , & A systematic review and meta-analysis of family history and risk of ovarian cancer. Br. J. Obstet. Gynaecol. 105, 493–499 (1998).

  3. 3.

    & Risk prediction models for familial breast cancer. Future Oncol. 2, 257–274 (2006).

  4. 4.

    et al. A genome-wide association study identifies a new ovarian cancer susceptibility l ocus on 9p22.2. Nat. Genet. 41, 996–1000 (2009).

  5. 5.

    et al. Common variants at 19p13 are associated with susceptibility to ovarian cancer. Nat. Genet. 42, 880–884 (2010).

  6. 6.

    et al. A genome-wide association study identifies susceptibility loci for ovarian cancer at 2q31 and 8q24. Nat. Genet. 42, 874–879 (2010).

  7. 7.

    et al. Epigenetic analysis leads to identification of HNF1B as a subtype-specific susceptibility gene for ovarian cancer. Nat. Comm. published online; doi:10.1038/ncomms2629 (27 March 2013).

  8. 8.

    et al. Mapping and analysis of chromatin state dynamics in nine human cell types. Nature 473, 43–49 (2011).

  9. 9.

    et al. Functional enhancers at the gene-poor 8q24 cancer-linked locus. PLoS Genet. 5, e1000597 (2009).

  10. 10.

    et al. Functional characterization of liver enhancers that regulate drug-associated transporters. Clin. Pharmacol. Ther. 89, 571–578 (2011).

  11. 11.

    , & An 8q24 gene desert variant associated with prostate cancer risk confers differential in vivo activity to a MYC enhancer. Genome Res. 20, 1191–1197 (2010).

  12. 12.

    , & Upregulation of c-MYC in cis through a large chromatin loop linked to a cancer risk-associated single-nucleotide polymorphism in colorectal cancer cells. Mol. Cell Biol. 30, 1411–1420 (2010).

  13. 13.

    , , , & ALIX-CHMP4 interactions in the human ESCRT pathway. Proc. Natl. Acad. Sci. USA 105, 7687–7691 (2008).

  14. 14.

    , , , & ESCRT-III governs the Aurora B-mediated abscission checkpoint through CHMP4C. Science 336, 220–225 (2012).

  15. 15.

    , & The regulation of the endosomal compartment by p53 the tumor suppressor gene. FEBS J. 276, 2201–2212 (2009).

  16. 16.

    et al. Genome-wide gene expression profiles of ovarian carcinoma: identification of molecular targets for the treatment of ovarian carcinoma. Mol. Med. Report 2, 365–384 (2009).

  17. 17.

    & The role of CALM-AF10 gene fusion in acute leukemia. Leukemia 22, 678–685 (2008).

  18. 18.

    et al. Nebulette is the second member of the nebulin family fused to the MLL gene in infant leukemia. Cancer Genet. Cytogenet. 198, 151–154 (2010).

  19. 19.

    & Nebulette mutations in cardiac remodeling: big effects from a small mechanosensor. J. Am. Coll. Cardiol. 56, 1503–1505 (2010).

  20. 20.

    et al. ESRRA-C11orf20 is a recurrent gene fusion in serous ovarian carcinoma. PLoS Biol. 9, e1001156 (2011).

  21. 21.

    et al. Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis. Nat. Genet. 42, 579–589 (2010).

  22. 22.

    et al. Genome-wide association study identifies a common variant associated with risk of endometrial cancer. Nat. Genet. 43, 451–454 (2011).

  23. 23.

    et al. Evaluation of association of HNF1B variants with diverse cancers: collaborative analysis of data from 19 genome-wide association studies. PLoS ONE 5, e10858 (2010).

  24. 24.

    , & Expression of hepatocyte nuclear factor-1β (HNF-1β) in clear cell tumors and endometriosis of the ovary. Mod. Pathol. 19, 83–89 (2006).

  25. 25.

    et al. Expression profiling in ovarian clear cell carcinoma: identification of hepatocyte nuclear factor-1β as a molecular marker and a possible molecular target for therapy of ovarian clear cell carcinoma. Am. J. Pathol. 163, 2503–2512 (2003).

  26. 26.

    Cancer Genome Atlas Research Network. Integrated genomic analyses of ovarian carcinoma. Nature 474, 609–615 (2011).

  27. 27.

    & Hepatocyte nuclear factor-1β (HNF-1β) in human urogenital organs: its expression and role in embryogenesis and tumorigenesis. Histol. Histopathol. 24, 1479–1486 (2009).

  28. 28.

    , , , & A catalogue of published genome-wide association studies. Genome.gov: National Institutes of Health National Human Genome Research Institute. <> (2013).

  29. 29.

    et al. A locus on 19p13 modifies risk of breast cancer in BRCA1 mutation carriers and is associated with hormone receptor-negative breast cancer in the general population. Nat. Genet. 42, 885–892 (2010).

  30. 30.

    et al. Large-scale genotyping identifies 41 new breast cancer susceptibility loci. Nat. Genet. published online; doi:10.1038/ng.2563 (27 March 2013).

  31. 31.

    et al. Senescent fibroblasts promote neoplastic transformation of partially transformed ovarian epithelial cells in a three-dimensional model of early stage ovarian cancer. Neoplasia 12, 317–325 (2010).

  32. 32.

    et al. LIN28B polymorphisms influence susceptibility to epithelial ovarian cancer. Cancer Res. 71, 3896–3903 (2011).

  33. 33.

    Artificial intelligence and global normalization methods for genotyping. US patent 7,035,740 (2008).

  34. 34.

    et al. A genotype calling algorithm for the Illumina BeadArray platform. Bioinformatics 23, 2741–2746 (2007).

  35. 35.

    , , , & GenoSNP: a variational Bayes within-sample SNP genotyping algorithm that does not require a reference population. Bioinformatics 24, 2209–2214 (2008).

  36. 36.

    , , & Estimating local ancestry in admixed populations. Am. J. Hum. Genet. 82, 290–303 (2008).

  37. 37.

    et al. Principal components analysis corrects for stratification in genome-wide association studies. Nat. Genet. 38, 904–909 (2006).

  38. 38.

    , , & Blindly using Wald's test can miss rare disease-causal variants in case-control association studies. Ann. Hum. Genet. 76, 168–177 (2012).

  39. 39.

    & Statistical Methods in Cancer Research. Volume 1—The Analysis of Case-Control Studies (International Agency for Research on Cancer, Lyon, 1980).

  40. 40.

    et al. COSMIC: mining complete cancer genomes in the Catalogue of Somatic Mutations in Cancer. Nucleic Acids Res. 39, D945–D950 (2011).

  41. 41.

    , , , & GeneMANIA: a real-time multiple association network integration algorithm for predicting gene function. Genome Biol. 9 (suppl. 1), S4 (2008).

  42. 42.

    et al. Histone modifications at human enhancers reflect global cell-type–specific gene expression. Nature 459, 108–112 (2009).

Download references

Acknowledgements

We thank all the individuals who took part in this study and all the researchers, clinicians and technical and administrative staff who made possible the many studies contributing to this work (a full list is provided in the Supplementary Note). The COGS project is funded through a European Commission's Seventh Framework Programme grant (agreement number 223175 - HEALTH-F2-2009-223175). 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 (PPD/RPCI.07). The scientific development and funding for this project were supported in part by the Genetic Associations and Mechanisms in Oncology (GAME-ON) and a National Cancer Institute Cancer Post-GWAS Initiative (U19-CA148112). Details of the funding of individual investigators and studies are provided in the Supplementary Note. This study made use of data generated by the Wellcome Trust Case Control consortium; funding for the project was provided by the Wellcome Trust under award 076113. A full list of the investigators who contributed to the generation of the data is available from the website (see URLs). The results published here are based in part on data generated by The Cancer Genome Atlas Pilot Project established by the National Cancer Institute and National Human Genome Research Institute; information about The Cancer Genome Atlas (TCGA) and the investigators and institutions who constitute the TCGA research network can be found on the website (see URLs).

Author information

Author notes

    • Paul D P Pharoah
    • , Ya-Yu Tsai
    • , Susan J Ramus
    •  & Catherine M Phelan

    These authors contributed equally to this work.

    • Joellen M Schildkraut
    •  & Thomas A Sellers

    These authors jointly directed this work.

Affiliations

  1. The Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK.

    • Paul D P Pharoah
    • , Jonathan P Tyrer
    • , Honglin Song
    • , Ed Dicks
    • , Qi Guo
    •  & Douglas F Easton
  2. The Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.

    • Paul D P Pharoah
    • , Joe Dennis
    •  & Douglas F Easton
  3. Department of Cancer Epidemiology, Division of Population Sciences, Moffitt Cancer Center, Tampa, Florida, USA.

    • Ya-Yu Tsai
    • , Catherine M Phelan
    • , Melissa Buckley
    • , Greg Bloom
    • , Renato S Carvalho
    • , Y Anne Chen
    • , Zhihua Chen
    • , David Fenstermacher
    • , Anxhela Gjyshi
    • , Jenny Permuth-Wey
    • , Xiaotao Qu
    • , Alvaro N A Monteiro
    •  & Thomas A Sellers
  4. Department of Preventive Medicine, Keck School of Medicine, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, California, USA.

    • Susan J Ramus
    • , Kate Lawrenson
    • , Howard Shen
    • , Rod Karevan
    • , Nathan Lee
    • , Janet Lee
    • , Malcolm C Pike
    • , David van den Berg
    • , Anna H Wu
    • , Celeste L Pearce
    •  & Simon A Gayther
  5. Department of Health Science Research, Division of Epidemiology, Mayo Clinic, Rochester, Minnesota, USA.

    • Ellen L Goode
    • , Brooke L Fridley
    • , Mine S Cicek
    •  & Robert A Vierkant
  6. Department of Community and Family Medicine, Duke University Medical Center, Durham, North Carolina, USA.

    • Rachel Weber
    •  & Joellen M Schildkraut
  7. Division of Biomedical Statistics and Informatics, Department of Health Science Research, Mayo Clinic, Rochester, Minnesota, USA.

    • Melissa C Larson
    •  & Sebastian M Armasu
  8. Centre Technologiques, McGill University, Montreal, Quebec, Canada.

    • Daniel C Tessier
    • , François Bacot
    •  & Daniel Vincent
  9. McGill University and Génome Québec Innovation Centre, Montreal, Quebec, Canada.

    • Daniel C Tessier
    • , François Bacot
    •  & Daniel Vincent
  10. Department of Laboratory Medicine and Pathology, Division of Anatomic Pathology, Mayo Clinic, Rochester, Minnesota, USA.

    • Julie M Cunningham
    •  & Vijayalakshmi Shridhar
  11. Department of Epidemiology, Biostatistics and Health Technology Assessment, Radboud University Medical Centre, Nijmegen, The Netherlands.

    • Katja K Aben
    •  & Lambertus A Kiemeney
  12. Comprehensive Cancer Center The Netherlands, Utrecht, The Netherlands.

    • Katja K Aben
    •  & Lambertus A Kiemeney
  13. Department of Epidemiology, Center for Cancer Genetics Research and Prevention, School of Medicine, University of California–Irvine, Irvine, California, USA.

    • Hoda Anton-Culver
    •  & Argyrios Ziogas
  14. N.N. Aleksandrov Byelorussian Institute for Oncology and Medical Radiology, Minsk, Belarus.

    • Natalia Antonenkova
  15. Cancer Epidemiology Centre, The Cancer Council Victoria, Melbourne, Victoria, Australia.

    • Laura Baglietto
    • , Graham Giles
    •  & Gianluca Severi
  16. Centre for Molecular, Environmental, Genetic and Analytical Epidemiology, The University of Melbourne, Melbourne, Victoria, Australia.

    • Laura Baglietto
    • , Graham Giles
    •  & Gianluca Severi
  17. The Cancer Institute of New Jersey, Robert Wood Johnson Medical School, New Brunswick, New Jersey, USA.

    • Elisa V Bandera
    •  & Lorna Rodriguez-Rodriguez
  18. Department of Gynecology and Obstetrics, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nuremberg, Comprehensive Cancer Center, Erlangen, Germany.

    • Matthias W Beckmann
    • , Peter A Fasching
    •  & Alexander Hein
  19. Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA.

    • Michael J Birrer
  20. Massachusetts General Hospital Cancer Center, Massachusetts General Hospital, Boston, Massachusetts, USA.

    • Michael J Birrer
  21. Gynaecology Research Unit, Hannover Medical School, Hannover, Germany.

    • Natalia Bogdanova
    •  & Thilo Dörk
  22. Cambridge Research Institute, Li Ka Shing Centre, Cambridge, UK.

    • James D Brenton
  23. Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USA.

    • Louise A Brinton
    • , Nicolas Wentzensen
    •  & Hannah P Yang
  24. Genome Sciences Centre, British Columbia Cancer Agency, Vancouver, British Columbia, Canada.

    • Angela Brooks-Wilson
  25. Department of Surgery and Cancer, Imperial College London, London, UK.

    • Robert Brown
    •  & James Flanagan
  26. Department of Pathology, Helsinki University Central Hospital, Helsinki, Finland.

    • Ralf Butzow
  27. Department of Obstetrics and Gynecology, Helsinki University Central Hospital, Helsinki, Finland.

    • Ralf Butzow
    • , Arto Leminen
    • , Heli Nevanlinna
    •  & Liisa M Pelttari
  28. Cancer Genetics Laboratory, Research Division, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.

    • Ian Campbell
  29. Department of Pathology, The University of Melbourne, Parkville, Victoria, Australia.

    • Ian Campbell
  30. Cancer Epidemiology Program, University of Hawaii Cancer Center, Honolulu, Hawaii, USA.

    • Michael E Carney
    • , Galina Lurie
    • , Pamela J Thompson
    •  & Marc T Goodman
  31. Division of Cancer Epidemiology, German Cancer Research Center, Heidelberg, Germany.

    • Jenny Chang-Claude
    • , Stefan Nickels
    •  & Anja Rudolph
  32. Division of Cancer Etiology and Genetics, National Cancer Institute, Bethesda, Maryland, USA.

    • Wong-Ho Chow
  33. Department of Microbiology and Preventive Medicine, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, California, USA.

    • Gerhard Coetzee
    •  & Houtan Noushmehr
  34. Department of Internal Medicine, University of New Mexico, Albuquerque, New Mexico, USA.

    • Linda S Cook
  35. Obstetrics and Gynecology Epidemiology Center, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.

    • Daniel W Cramer
    • , Kathryn L Terry
    •  & Allison F Vitonis
  36. Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA.

    • Daniel W Cramer
    • , Elizabeth M Poole
    • , Kathryn L Terry
    •  & Shelley S Tworoger
  37. International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland.

    • Cezary Cybulski
    • , Jacek Gronwald
    • , Anna Jakubowska
    •  & Jan Lubiński
  38. Department of Molecular Pathology, The Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland.

    • Agnieszka Dansonka-Mieszkowska
    • , Jolanta Kupryjanczyk
    •  & Iwona K Rzepecka
  39. Division of Gynecologic Oncology, Department of Obstetrics and Gynaecology, Leuven Cancer Institute, Leuven, Belgium.

    • Evelyn Despierre
    • , Sandrina Lambrechts
    •  & Ignace Vergote
  40. Section of Biostatistics and Epidemiology, The Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire, USA.

    • Jennifer A Doherty
  41. Department of Gynecology and Gynecologic Oncology, Dr. Horst Schmidt Kliniken Wiesbaden, Wiesbaden, Germany.

    • Andreas du Bois
    • , Philipp Harter
    •  & Florian Heitz
  42. Department of Gynecology and Gynecologic Oncology, Kliniken Essen-Mitte/ Evang. Huyssens-Stiftung/ Knappschaft, Essen, Germany.

    • Andreas du Bois
    • , Philipp Harter
    •  & Florian Heitz
  43. Department of Gynecology, Jena University Hospital, Jena, Germany.

    • Matthias Dürst
    •  & Ingo Runnebaum
  44. Faculty of Medicine, University of Southampton, University Hospital Southampton, Southampton, UK.

    • Diana Eccles
  45. Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.

    • Robert Edwards
    •  & Francesmary Modugno
  46. Women's Cancer Program, Magee-Womens Research Institute, Pittsburg, Pennsylvania, USA.

    • Robert Edwards
  47. Institute of Human Genetics, Friedrich-Alexander-University Erlangen-Nuremberg, Erlangen, Germany.

    • Arif B Ekici
  48. Department of Medicine, Division of Hematology and Oncology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, USA.

    • Peter A Fasching
    •  & Gottfried E Konecny
  49. Department of Epidemiology, Shanghai Cancer Institute, Shanghai, China.

    • Yu-Tang Gao
  50. Division of Genetics and Epidemiology, Institute of Cancer Research, Sutton, UK.

    • Montserrat Garcia-Closas
  51. Breakthrough Breast Cancer Research Centre, Institute of Cancer Research, London, UK.

    • Montserrat Garcia-Closas
  52. Gynaecological Cancer Research Centre, University College London Elizabeth Garrett Anderson Institute for Women's Health, London, UK.

    • Aleksandra Gentry-Maharaj
    •  & Usha Menon
  53. Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Victoria, Australia.

    • Graham Giles
  54. Gynecological Oncology Unit, The Royal Marsden Hospital, London, UK.

    • Martin Gore
  55. Department of Gynecology and Obstetrics, Haukeland University Hospital, Bergen, Norway.

    • Mari K Halle
    • , Camilla Krakstad
    • , Helga B Salvesen
    •  & Elisabeth Wik
  56. Department of Clinical Medicine, University of Bergen, Bergen, Norway.

    • Mari K Halle
    • , Camilla Krakstad
    • , Helga B Salvesen
    •  & Elisabeth Wik
  57. Clinics of Obstetrics and Gynaecology, Hannover Medical School, Hannover, Germany.

    • Peter Hillemanns
  58. Department of Biochemistry and Molecular Biology, Oregon Health and Science University, Portland, Oregon, USA.

    • Maureen Hoatlin
  59. Virus, Lifestyle and Genes, Danish Cancer Society Research Center, Copenhagen, Denmark.

    • Estrid Høgdall
    • , Allan Jensen
    •  & Susanne Krüger Kjaer
  60. Molecular Unit, Department of Pathology, Herlev Hospital, University of Copenhagen, Copenhagen, Denmark.

    • Estrid Høgdall
  61. The Juliane Marie Centre, Department of Obstetrics and Gynecology, Rigshospitalet, Copenhagen, Denmark.

    • Claus K Høgdall
    • , Susanne Krüger Kjaer
    •  & Lene Lundvall
  62. Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya, Japan.

    • Satoyo Hosono
    • , Keitaro Matsuo
    •  & Kazuo Tajima
  63. Department of Medical Oncology, Mayo Clinic, Rochester, Minnesota, USA.

    • Kimberly R Kalli
  64. Women's Cancer Program at the Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA.

    • Beth Y Karlan
  65. Department of Population Health Research, Alberta Health Services–Cancer Care, Calgary, Alberta, Canada.

    • Linda E Kelemen
  66. Department of Medical Genetics, University of Calgary, Calgary, Alberta, Canada.

    • Linda E Kelemen
  67. Department of Urology, Radboud University Medical Centre, Nijmegen, The Netherlands.

    • Lambertus A Kiemeney
  68. Vesalius Research Center, University of Leuven, Leuven, Belgium.

    • Diether Lambrechts
  69. Cancer Control Research, BC Cancer Agency, Vancouver, British Columbia, Canada.

    • Nhu D Le
  70. Department of Obstetrics and Gynaecology, University Malaya Medical Centre, University Malaya, Kuala Lumpur, Malaysia.

    • Boon Kiong Lim
    •  & Yin Ling Woo
  71. The Maria Sklodowska-Curie Memorial Cancer Center, Warsaw, Poland.

    • Jolanta Lissowska
  72. Department of Gynaecology, Radboud University Medical Centre, Nijmegen, The Netherlands.

    • Leon F A G Massuger
    •  & Anne M van Altena
  73. Department of Health Research and Policy–Epidemiology, Stanford University School of Medicine, Stanford, California, USA.

    • Valerie McGuire
    • , Weiva Sieh
    •  & Alice S Whittemore
  74. Dalla Lana School of Public Health, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.

    • John R McLaughlin
  75. Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada.

    • John R McLaughlin
  76. Department of Epidemiology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.

    • Francesmary Modugno
  77. Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, New York, USA.

    • Kirsten B Moysich
    •  & Kunle Odunsi
  78. Department of Gynecologic Oncology, Aichi Cancer Center Central Hospital, Nagoya, Japan.

    • Toru Nakanishi
  79. Women's College Research Institute, University of Toronto, Toronto, Ontario, Canada.

    • Steven A Narod
  80. The University of Texas School of Public Health, Houston, Texas, USA.

    • Roberta B Ness
  81. University of Southern California Epigenome Center, Keck School of Medicine, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, California, USA.

    • Houtan Noushmehr
    •  & Hui Shen
  82. Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, New York, USA.

    • Sara Olson
    • , Irene Orlow
    •  & Malcolm C Pike
  83. The Beatson West of Scotland Cancer Centre, Glasgow, UK.

    • James Paul
  84. Department of Obstetrics and Gynecology, Oregon Health and Science University, Portland, Oregon, USA.

    • Tanja Pejovic
  85. Knight Cancer Institute, Oregon Health and Science University, Portland, Oregon, USA.

    • Tanja Pejovic
  86. Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.

    • Elizabeth M Poole
    •  & Shelley S Tworoger
  87. Department of Epidemiology and Public Health, Yale University School of Public Health and School of Medicine, New Haven, Connecticut, USA.

    • Harvey A Risch
  88. Department of Epidemiology, University of Washington, Seattle, Washington, USA.

    • Mary Anne Rossing
  89. Program in Epidemiology, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.

    • Mary Anne Rossing
  90. Institut für Humangenetik, Wiesbaden, Germany.

    • Ira Schwaab
  91. Vanderbilt Epidemiology Center, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.

    • Xiao-Ou Shu
    •  & Wei Zheng
  92. Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.

    • Xiao-Ou Shu
    •  & Wei Zheng
  93. Genetic Epidemiology Laboratory, Department of Pathology, The University of Melbourne, Melbourne, Victoria, Australia.

    • Melissa C Southey
  94. Molecular and Medical Genetics, Oregon Health and Science University, Portland, Oregon, USA.

    • Paul Spellman
  95. Cancer Research Initiatives Foundation, Sime Darby Medical Centre, Subang Jaya, Malaysia.

    • Soo-Hwang Teo
    •  & Famida Zulkifli
  96. University Malaya Medical Centre, University Malaya, Kuala Lumpur, Malaysia.

    • Soo-Hwang Teo
    •  & Famida Zulkifli
  97. Department of Obstetrics, Gynecology and Oncology, IInd Faculty of Medicine, Warsaw Medical University, Warsaw, Poland.

    • Agnieszka Timorek
  98. Department of Obstetrics and Gynaecology, Brodnowski Hospital, Warsaw, Poland.

    • Agnieszka Timorek
  99. Department of Obstetrics and Gynecology, University of Ulm, Ulm, Germany.

    • Shan Wang-Gohrke
  100. Department of Obstetrics and Gynecology, Mayo Clinic, Rochester, Minnesota, USA.

    • Boris Winterhoff
  101. Department of Epidemiology and Biostatistics, Karolinska Istitutet, Stockholm, Sweden.

    • Per Hall
  102. Department of Obstetrics and Gynecology, Duke University Medical Center, Durham, North Carolina, USA.

    • Andrew Berchuck
  103. Cancer Division, Queensland Institute of Medical Research, Herston, Queensland, Australia.

    • Georgia Chenevix-Trench
  104. Department of Statistics, Duke University, Durham, North Carolina, USA.

    • Edwin Iversen
  105. Cancer Prevention, Detection and Control Research Program, Duke Cancer Institute, Durham, North Carolina, USA.

    • Joellen M Schildkraut

Consortia

  1. Australian Cancer Study

    A list of members is provided in the Supplementary Note.

  2. Australian Ovarian Cancer Study Group

    A list of members is provided in the Supplementary Note.

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Contributions

Writing group: P.D.P.P., Y.-Y.T., C.M.P., S.J.R., J.M.S., T.A.S., B.L.F., E.L.G., A.N.A.M. and S.A.G. All authors read and approved the final manuscript. Provision of samples and data from contributing studies: K.L., M.P., J.P.T., H. Shen, R.W., R.K., M.C.L., H. Song, D.C.T., F.B., D.V., J.M.C., J.D., E. Dicks, K.K.A., H.A.-C., N.A., S.M.A., L.B., E.V.B., M.W.B., M.J.B., G.B., N.B., J.D.B., L.A.B., A.B.-W., R. Brown, R. Butzow, I.C., M.E.C., R.S.C., J.C.-C., Y.A.C., Z.C., A.D.-M., E. Despierre, J.A.D., T.D., A.d.B., M.D., D.E., R.E., A.B.E., P.A.F., D.F., J.F., Y.-T.G., M.G.-C., A.G.-M., G.G., A.G., M.G., J.G., Q.G., M.K.H., P. Harter, A.H., F.H., P. Hillemanns, M.H., E.H., C.K.H., S.H., A. Jakubowska, A. Jensen, K.R.K., B.Y.K., L.E.K., L.A.K., S.K.K., G.E.K., C.K., J.K., D.L., S.L., N.D.L., N.L., J. Lee, A.L., B.K.L., J. Lissowska, J. Lubinński, L.L., G.L., L.F.A.G.M., K.M., V.M., J.R.M., U.M., F.M., K.B.M., T.N., S.A.N., R.B.N., H. Nevanlinna, S.N., H. Noushmehr, K.O., S.O., I.O., J.P., T.P., L.M.P., J.P.-W., M.C.P., E.M.P., X.Q., H.A.R., L.R.-R., M.A.R., A.R., I.R., I.K.R., H.B.S., I.S., G.S., H. Shen, V.S., X.-O.S., W.S., M.C.S., P.S., K.T., S.-H.T., K.L.T., P.J.T., A.T., S.S.T., A.M.v.A., D.v.d.B., I.V., R.A.V., A.F.V., S.W.-G., N.W., A.S.W., E.W., B.W., Y.L.W., A.H.W., H.P.Y., W.Z., A.Z., F.Z., M.T.G., P. Hall, D.F.E., C.L.P., A.B., G.C.-T., E.I. and J.M.S. Bioinformatics and data management: J.D., E. Dicks, Z.C. and R.W. Data analysis: J.P.T., Q.G., Y.-Y.T. and B.L.F. Preparation of samples for genotyping: S.J.R. and C.M.P. Genotyping: J.M.C., D.C.T., F.B. and D.V. Functional analyses: S.A.G., M.B., A.N.A.M., B.L.F., K.L., H. Shen, E.L.G., S.J.R., Y.A.C. and M.L.C.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Paul D P Pharoah.

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    Supplementary Text and Figures

    Supplementary Tables 1–5, Supplementary Figures 1–13 and Supplementary Note

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DOI

https://doi.org/10.1038/ng.2564

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