Journal article

Identification and molecular characterization of a new ovarian cancer susceptibility locus at 17q21.31

Jennifer Permuth-Wey, Kate Lawrenson, Howard C Shen, Aneliya Velkova, Jonathan P Tyrer, Zhihua Chen, Hui-Yi Lin, Y Ann Chen, Ya-Yu Tsai, Xiaotao Qu, Susan J Ramus, Rod Karevan, Janet Lee, Nathan Lee, Melissa C Larson, Katja K Aben, Hoda Anton-Culver, Natalia Antonenkova, Antonis C Antoniou, Sebastian M Armasu Show all

NATURE COMMUNICATIONS | NATURE RESEARCH | Published : 2013

Abstract

Epithelial ovarian cancer (EOC) has a heritable component that remains to be fully characterized. Most identified common susceptibility variants lie in non-protein-coding sequences. We hypothesized that variants in the 3' untranslated region at putative microRNA (miRNA)-binding sites represent functional targets that influence EOC susceptibility. Here, we evaluate the association between 767 miRNA-related single-nucleotide polymorphisms (miRSNPs) and EOC risk in 18,174 EOC cases and 26,134 controls from 43 studies genotyped through the Collaborative Oncological Gene-environment Study. We identify several miRSNPs associated with invasive serous EOC risk (odds ratio=1.12, P=10(-8)) mapping to ..

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Grants

Awarded by European Commission


Awarded by US National Cancer Institute


Awarded by Genetic Associations and Mechanisms in Oncology (GAME-ON): a NCI Cancer Post-GWAS Initiative


Awarded by Wellcome Trust


Awarded by American Cancer Society Early Detection Professorship


Awarded by Canadian Institutes of Health Research


Awarded by American Cancer Society


Awarded by California Cancer Research Program


Awarded by Canadian Institutes for Health Research


Awarded by Cancer Research UK


Awarded by Danish Cancer Society


Awarded by Imperial Experimental Cancer Research Centre


Awarded by Polish Ministry of Science and Higher Education


Awarded by US National Cancer Institutes


Awarded by NIH/National Center for Research Resources/General Clinical Research Grant


Awarded by US Army Medical Research and Materiel Command


Awarded by Department of Defense Ovarian Cancer Research Program


Awarded by National Health and Medical Research Council of Australia


Awarded by German Federal Ministry of Education and Research of Germany Programme of Clinical Biomedical Research


Awarded by state of Baden-Wurttemberg through Medical Faculty of the University of Ulm


Awarded by Malaysian Ministry of Higher Education


Awarded by Lon V. Smith Foundation


Awarded by U.S. Natl Canc Inst


Awarded by The Francis Crick Institute


Awarded by DIVISION OF CANCER CONTROL &POPULATION SCIENCE


Awarded by DIVISION OF CANCER PREVENTION AND CONTROL


Awarded by NATIONAL CANCER INSTITUTE


Awarded by NATIONAL CENTER FOR RESEARCH RESOURCES


Funding Acknowledgements

We thank all the individuals who participated in this research and all the researchers, clinicians and administrative staff who have made possible the many studies contributing to this work. In particular, we thank D. Bowtell, P. Webb, A. deFazio, D. Gertig, A. Green, P. Parsons, N. Hayward and D. Whiteman (AUS); D. L. Wachter, S. Oeser, S. Landrith (BAV); G. Peuteman, T. Van Brussel and D. Smeets (BEL); the staff of the genotyping unit, S LaBoissiere and F Robidoux (McGill University and Genome Quebec Innovation Centre); U. Eilber and T. Koehler (GER); L. Gacucova (HMO); P. Schuermann, F. Kramer, T.-W. Park-Simon, K. Beer-Grondke and D. Schmidt (HJO); G. L. Keeney, C. Hilker and J. Vollenweider (MAY); the state cancer registries of AL, AZ, AR, CA, CO, CT, DE, FL, GA, HI, ID, IL, IN, IA, KY, LA, ME, MD, MA, MI, NE, NH, NJ, NY, NC, ND, OH, OK, OR, PA, RI, SC, TN, TX, VA, WA and WYL (NHS); L. Paddock, M. King, U. Chandran, A. Samoila and Y. Bensman (NJO); M. Insua and R. Evey (Moffitt); The Sherie Hildredth Ovarian Cancer Foundation (ORE); M. Sherman, A. Hutchinson, N. Szeszenia-Dabrowska, B. Peplonska, W. Zatonski, A. Soni, P. Chao and M. Stagner (POL); C. Luccarini, P. Harrington the SEARCH team and ECRIC (SEA); the Scottish Gynaecological Clinical Trails group and SCOTROC1 investigators (SRO); W-H. Chow, Y.-T. Gao, G. Yang, B.-T. Ji (SWH); I. Jacobs, M. Widschwendter, E. Wozniak, N. Balogun, A. Ryan and J. Ford (UKO); M. Notaridou (USC); C. Pye (UKR); and V. Slusher (U19). 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 in part supported by the US National Cancer Institute (R01-CA-114343 and R01-CA114343-S1) and the Genetic Associations and Mechanisms in Oncology (GAME-ON): a NCI Cancer Post-GWAS Initiative (U19-CA148112). This study made use of the 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 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/. D. F. E. is a Principal Research Fellow of Cancer Research UK, G.C.-T. and P. M. W. are supported by the National Health and Medical Research Council. B. K. holds an American Cancer Society Early Detection Professorship (SIOP-06-258-01-COUN). L. E. K. is supported by a Canadian Institutes of Health Research Investigator award (MSH-87734). M. G. acknowledges NHS funding to the NIHR Biomedical Research Centre. A. C. A. is Cancer Research UK Senior Cancer Research Fellow.Funding of the constituent studies was provided by the American Cancer Society (CRTG-00-196-01-CCE); the California Cancer Research Program (00-01389V-20170, N01-CN25403, 2II0200); the Canadian Institutes for Health Research (MOP-86727); Cancer Council Victoria; Cancer Council Queensland; Cancer Council New South Wales; Cancer Council South Australia; Cancer Council Tasmania; Cancer Foundation of Western Australia; the Cancer Institute of New Jersey; Cancer Research UK (C490/A6187, C490/A10119, C490/A10124, C536/A13086, C536/A6689); the Celma Mastry Ovarian Cancer Foundation; the Danish Cancer Society (94-222-52); the Norwegian Cancer Society, Helse Vest, the Norwegian Research Council; ELAN Funds of the University of Erlangen-Nuremberg; the Eve Appeal; the Helsinki University Central Hospital Research Fund; Imperial Experimental Cancer Research Centre (C1312/A15589); the Ovarian Cancer Research Fund; Nationaal Kankerplan of Belgium; Grant-in-Aid for the Third Term Comprehensive 10-Year Strategy for Cancer Control from the Ministry of Health Labour and Welfare of Japan; the L & S Milken Foundation; the Radboud University Nijmegen Medical Centre; the Polish Ministry of Science and Higher Education (4 PO5C 028 14, 2 PO5A 068 27); the Roswell Park Cancer Institute Alliance Foundation; the US National Cancer Institute (K07-CA80668, K07-CA095666, K07-CA143047, K22-CA138563, N01-CN55424, N01-PC067001, N01-PC035137, P01-CA017054, P01-CA087696, P50-CA105009, P50-CA136393, R01-CA014089, R01-CA016056, R01-CA017054, R01-CA049449, R01-CA050385, R01-CA054419, R01-CA058598, R01-CA058860, R01-CA061107, R01-CA061132, R01-CA063678, R01-CA063682, R01-CA064277, R01-CA067262, R01-CA071766, R01-CA074850, R01-CA076016, R01-CA080742, R01-CA080978, R01-CA087538, R01-CA092044, R01-095023, R01-CA106414, R01-CA122443, R01-CA136924, R01-CA112523, R01-CA114343, R01-CA126841, R01-CA149429, R03-CA113148, R03-CA115195, R37-CA070867, R01-CA83918, U01-CA069417, U01-CA071966, P30-CA15083, PSA 042205, and Intramural research funds); the NIH/National Center for Research Resources/General Clinical Research Grant (M01-RR000056); the US Army Medical Research and Materiel Command (DAMD17-98-18659, DAMD17-01-1-0729, DAMD17-02-1-0666, DAMD17-02-1-0669, W81XWH-101- 02802); the Department of Defense Ovarian Cancer Research Program (W81XWH-07-1-0449); 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-Wurttemberg through Medical Faculty of the University of Ulm (P. 685); the German Cancer Research Center; Pomeranian Medical University; the Minnesota Ovarian Cancer Alliance; the Mayo Foundation; the Fred C. and Katherine B. Andersen Foundation; the Malaysian Ministry of Higher Education (UM. C/HlR/MOHE/06) and Cancer Research Initiatives Foundation; the Lon V. Smith Foundation (LVS-39420); the Oak Foundation; the OHSU Foundation; the Mermaid I project; the Rudolf-Bartling Foundation; the UK National Institute for Health Research Biomedical Research Centres at the University of Cambridge, Imperial College London, University College Hospital 'Womens Health Theme' and the Royal Marsden Hospital; WorkSafeBC.