Common variants at 19p13 are associated with susceptibility to ovarian cancer

A Corrigendum to this article was published on 01 January 2016

This article has been updated

Abstract

Epithelial ovarian cancer (EOC) is the leading cause of death from gynecological malignancy in the developed world, accounting for 4% of the deaths from cancer in women1. We performed a three-phase genome-wide association study of EOC survival in 8,951 individuals with EOC (cases) with available survival time data and a parallel association analysis of EOC susceptibility. Two SNPs at 19p13.11, rs8170 and rs2363956, showed evidence of association with survival (overall P = 5 × 10−4 and P = 6 × 10−4, respectively), but they did not replicate in phase 3. However, the same two SNPs demonstrated genome-wide significance for risk of serous EOC (P = 3 × 10−9 and P = 4 × 10−11, respectively). Expression analysis of candidate genes at this locus in ovarian tumors supported a role for the BRCA1-interacting gene C19orf62, also known as MERIT40, which contains rs8170, in EOC development.

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Figure 1: Genomic and transcript analysis of C19orf62 and ANKLE1 in the 19p13 ovarian cancer susceptibility region.

Change history

  • 07 December 2015

    In the version of this article initially published, the name of author Angela Brooks-Wilson was spelled incorrectly in the author list. The error has been corrected in the HTML and PDF versions of the article.

  • 01 January 2016

    Nat. Genet. 42, 880–884 (2010); published online 19 September 2010; corrected after print 7 December 2015 In the version of this article initially published, the name of author Angela Brooks-Wilson was spelled incorrectly in the author list. The error has been corrected in the HTML and PDF versions of the article.

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Acknowledgements

We thank all the individuals who took part in this study and all the researchers, clinicians and administrative staff who have made possible the many studies contributing to this work. In particular we thank A. Ryan and J. Ford (United Kingdom Ovarian Cancer Population Study (UKOPS)); J. Morrison, P. Harrington and the Studies of Epidemiology and Risk Factors in Cancer Heredity (SEARCH) team (SEA); U. Eilber and T. Koehler (German Ovarian Cancer Study (GER)); D. Bowtell, A. deFazio, D. Gertig and A. Green (Australian Ovarian Cancer Study (AOCS)); A. Green, P. Parsons, N. Hayward and D. Whiteman (Australian Cancer Study (ACS)); L. Gacucova (Hannover-Minsk Ovarian Cancer Study (HMOCS)); S. Haubold, P. Schürmann, F. Kramer, W. Zheng, T.-W. Park-Simon, K. Beer-Grondke and D. Schmidt (Hannover-Jena Ovarian Cancer Study (HJOCS)); and L. Brinton, M. Sherman, A. Hutchinson, N. Szeszenia-Dabrowska, B. Peplonska, W. Zatonski, A. Soni, P. Chao and M. Stagner (NCI Ovarian Cancer Case-Control Study in Poland (POL2)).

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). This study makes use of data generated by the Wellcome Trust Case-Control consortium. A full list of the investigators who contributed to the generation of the data is available from http://www.wtccc.org.uk/. Funding for the project was provided by the Wellcome Trust under award 076113. 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 K. Sladek Smith. The results published here are in part based upon data generated by The Cancer Genome Atlas Pilot Project established by the National Cancer Institute and National Human Genome Research Institute. Information about TCGA and the investigators and institutions who constitute the TCGA research network can be found at http://cancergenome.nih.gov/. S.J.R. is supported by the Mermaid/Eve Appeal. G.C.-T. and P.M.W. are supported by the National Health and Medical Research Council. P.A.F. is supported by the Deutsche Krebshilfe. M.E.G. acknowledges National Health Service funding to the National Institutes of Health Research Centre at the Royal Marsden Hospital, and D.F.E. is a Principal Research Fellow of Cancer Research UK. Funding of the constituent studies was provided by the Danish Cancer Society, the Ovarian Cancer Research Fund (PPD/RPCI.07), the Roswell Park Cancer Institute Alliance Foundation, the US National Cancer Institute (CA58860, CA92044, P50CA105009, R01CA122443, R01CA126841-01, R01CA16056, R01CA61107, R01CA71766, R01CA054419, R01CA114343, R01CA87538, R01CA112523, R01CA58598, N01CN55424, N01PC35137 and Intramural research funds), the US Army Medical Research and Material Command (DAMD17-01-1-0729), Cancer Council Victoria, Cancer Council Queensland, Cancer Council New South Wales, Cancer Council South Australia, Cancer Council Tasmania and Cancer Foundation of Western Australia, the National Health and Medical Research Council of Australia (199600 and 400281), the German Federal Ministry of Education and Research of Germany Programme of Clinical Biomedical Research (01 GB 9401), the state of Baden-Württemberg through Medical Faculty of the University of Ulm (P.685), the Mayo Foundation, the Lon V. Smith Foundation (LVS-39420), the Oak Foundation, the University College Hospital National Institute for Health Research Biomedical Research Centre and the Royal Marsden Hospital Biomedical Research Centre.

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P.D.P.P., S.A.G. and D.F.E. designed the overall study and obtained financial support. P.D.P.P., S.A.G., S.J.R. and H.S. coordinated the studies used in phase 1 and phase 2. H.S., K.L.B., G.C.-T. and E.L.G. coordinated phase 3. J.T. and K.L.B. conducted primary phase 1 and phase 2 analysis and phase 3 SNP selection. K.L.B. conducted phase 3 and combined data statistical analyses. H.S., J.B. and J.M.C. conducted phase 3 genotyping. S.A.G., M.N., C.J. and T.S. designed and performed the functional analyses. The remaining authors coordinated contributing studies. K.L.B. and P.D.P.P. drafted the manuscript with substantial input from S.A.G., H.S. and S.J.R. All authors contributed to the final draft.

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Correspondence to Paul D P Pharoah.

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The authors declare no competing financial interests.

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Supplementary Note, Supplementary Tables 1–6 and Supplementary Figures 1–4 (PDF 692 kb)

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Bolton, K., Tyrer, J., Song, H. et al. Common variants at 19p13 are associated with susceptibility to ovarian cancer. Nat Genet 42, 880–884 (2010). https://doi.org/10.1038/ng.666

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