Journal article

Genome-wide Analysis Identifies Novel Loci Associated with Ovarian Cancer Outcomes: Findings from the Ovarian Cancer Association Consortium

Sharon E Johnatty, Jonathan P Tyrer, Siddhartha Kar, Jonathan Beesley, Yi Lu, Bo Gao, Peter A Fasching, Alexander Hein, Arif B Ekici, Matthias W Beckmann, Diether Lambrechts, Els Van Nieuwenhuysen, Ignace Vergote, Sandrina Lambrechts, Mary Anne Rossing, Jennifer A Doherty, Jenny Chang-Claude, Francesmary Modugno, Roberta B Ness, Kirsten B Moysich Show all

CLINICAL CANCER RESEARCH | AMER ASSOC CANCER RESEARCH | Published : 2015

Abstract

PURPOSE: Chemotherapy resistance remains a major challenge in the treatment of ovarian cancer. We hypothesize that germline polymorphisms might be associated with clinical outcome. EXPERIMENTAL DESIGN: We analyzed approximately 2.8 million genotyped and imputed SNPs from the iCOGS experiment for progression-free survival (PFS) and overall survival (OS) in 2,901 European epithelial ovarian cancer (EOC) patients who underwent first-line treatment of cytoreductive surgery and chemotherapy regardless of regimen, and in a subset of 1,098 patients treated with ≥ 4 cycles of paclitaxel and carboplatin at standard doses. We evaluated the top SNPs in 4,434 EOC patients, including patients from The Ca..

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Grants

Awarded by Army Medical Research and Materiel Command


Awarded by National Health and Medical Research Council of Australia


Awarded by AOCS Cancer Council


Awarded by NIH


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


Awarded by U.S. National Cancer Institute


Awarded by US Army Medical Research and Materiel Command


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


Awarded by American Cancer Society


Awarded by National Center for Advancing Translational Sciences (NCATS)


Awarded by European Communitys Seventh Framework Programme


Awarded by Cancer Research UK


Awarded by National institutes of Health


Awarded by Post-Cancer GWAS initiative


Awarded by Department of Defence


Awarded by NCI CCSG award


Awarded by National Cancer Institute


Awarded by Danish Cancer Society


Awarded by Department of Defense


Awarded by Department of Defense CDMRP


Awarded by NCI


Awarded by Imperial Experimental Cancer Research Centre


Awarded by Australian National Health and Medical Research Council


Awarded by Cancer Institute NSW


Awarded by California Cancer Research Program



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 ADVANCING TRANSLATIONAL SCIENCES


Awarded by NATIONAL CENTER FOR RESEARCH RESOURCES


Awarded by Medical Research Council


Awarded by The Francis Crick Institute


Funding Acknowledgements

AUS studies (Australian Ovarian Cancer Study and the Australian Cancer Study) were funded by Army Medical Research and Materiel Command (DAMD17-01-1-0729); National Health St Medical Research Council of Australia; Cancer Councils of New South Wales, Victoria, Queensland, South Australia, and Tasmania; Cancer Foundation of Western Australia; and National Health and Medical Research Council of Australia (199600 and 400281). The grant numbers for AOCS Cancer Council funding are as follows: Multi State Application Numbers 191, 211, and 182. The Bavarian study (BAY) WaS supported by Fl AN Funds of the University of Erlangen Nuremberg. The Belgian study (BEL) was funded by Nationaal Kankerplan. The Diseases of the Ovary and their Evaluation (DOV) study was funded by NIH R01-CA112523 and R01-CA87538. The German Ovarian Cancer Study (GER) was supported by the German Federal Ministry of Education and Research of Germany, Programme of Clinical Biomedical Research (01 GB 9401), and the German Cancer Research Center (DKFZ). The Hawaii Ovarian Cancer Study (HAW) was supported by R01 CA 058598. The Hormones and Ovarian Cancer Prediction study (HOP) was supported by U.S. National Cancer Institute: K07-CA80668, R01CA095023, P50-CA159981, 1101-CAl26841; US Army Medical Research and Materiel Command: DAMD17-02-1-0669; and NIH/National Center for Research Resources/ General Clinical Research Center grant MO1- RR000056. The Women's Cancer Program (LAX) was supported by the American Cancer Society Early Detection Professorship (120950-SIOP-06-258-06-COUN) and the National Center for Advancing Translational Sciences (NCATS), Grant UL1TR000124. The Mayo Clinic Case-Only Ovarian Cancer Study (MAC) was funded by the NIH (R01-CA122443, P30-CA15083, P50-CA136393). The Mayo Clinic Ovarian Cancer Case Control Study (MAY) was supported by NIH (R01-CA122443, P30-CA15083, P50-CA136393); Mayo Foundation; Minnesota Ovarian Cancer Alliance; Fred C. and Katherine B. Andersen Foundation. The MALOVA study (MAL) was funded by the National Cancer Institute (grant R01-CA 61107), the Danish Cancer Society (grant 94-22252), and the Mermaid I project. The North Carolina Ovarian Cancer Study (NCO) was supported by NIH (R01-CA76016) and the Department of Defense (DAMD17-02-1-0666). The New England based Case Control Study of Ovarian Cancer (NEC) was supported by NIH grants R01 CA 054419-10 and P50 CA105009, and Department of Defense CDMRP grant W81XWH-10-1-0280. The New Jersey Ovarian Cancer Study (NJO) was funded by the NCI (NIH-K07 CA095666, R01-CA83918, NIH-K22-CA138563, and P30-CA072720) and the Cancer Institute of New Jersey. The Oregon study (ORE) Was funded hy the Sherie Hildreth Ovarian Cancer Research Fund and the OHSU Foundation. The Polish Ovarian Cancer Case Control Study (POL) was funded by Intramural Research Program of the NCI. The SEARCH study (SEA) was supported by Cancer Research UK (C490/A8339, C490/A10119, C490/A10124, and C490/A16561) and UK National Institute for Health Research Biomedical Research Centre at the University, of Cambridge. The Scottish Randomised Trial in Ovarian Cancer (SRO) was funded by Cancer Research UK (C536/A13086, C536/A6689) and Imperial Experimental Cancer Research Centre (C1312/A15589). The Gynaecological Oncology Biobank at Westmead (WHMH) is a member of the Australasian Biospecimen Network-Oncology group, funded by the Australian National Health and Medical Research Council Enabling Grants ID 310670 and ID 628903 and the Cancer Institute NSW Grant ID 12/RIG/I-17.The United Kingdom Ovarian cancer Population Study (LIKO) was funded by The Eve Appeal (The Oak Foundation) and supported by the National Institute for Health Research University College London Hospitals Biomedical Research Centre. The UK Familial Ovarian Cancer Registry (LIKO) Cancer Research UK (C490/A6187); UK National Institute for Health Research Biomedical Research Centers kit the University of Cambridge. The Los Angeles County Case Control Studies of Ovarian Cancer-3 (USC) P01CA17054, P30CA14089, R01CA61132, N01PC67010, R03CA113148, R03CA115195, N01CN025403, and California Cancer Research Program (00-01389V-20170, 2II0200). The Warsaw Ovarian Cancer Study (WOC) Polish Ministry of Science and Higher Education (4 PO5C 028 14, 2 PO5A 068 27), The Maria Sklodowska Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland.Anna deFazio was funded by the University of Sydney Cancer Research Fund and the Cancer institute NSW through the Sydney West Translational Cancer Research Centre. Dr. RV. Marian was supported hy American Cancer Society Early Detection Professorship (SIOP-06-258-01-COUN) and the National Center for Advancing Translational Sciences (NCATS), Grant ULITR000124.I. Orlow was supported by NCI CCSG award (P30-CA008748).Funding for the iCOGS infrastructure came from the European Communitys Seventh Framework Programme under grant agreement no 223175 (HEALTH F2-2009-223175; COGS), Cancer Research UK (CI287/A10118, CI287/A 10710, C12292/AI1174, C1281/AI2014, C5047/A8384, C5047/AI5007, C5047/AI0692, C8197/AI6565), the National institutes of Health (CA128978) and Post-Cancer GWAS initiative (1U19 CA148537, 1U19 CA148065, and 1U119 CA148112 - the GAME-ON initiative), the Department of Defence (W81XWH-10-1-0341), the Canadian Institutes of Health Research (CIHR) for the CIHR Team in Familial Risks of Breast Cancer, Komen Foundation for the Cure, the Breast Cancer Research Foundation and the Ovarian Cancer Research Fund.