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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2013-04

AUTHORS

Paul D P Pharoah, Ya-Yu Tsai, Susan J Ramus, Catherine M Phelan, Ellen L Goode, Kate Lawrenson, Melissa Buckley, Brooke L Fridley, Jonathan P Tyrer, Howard Shen, Rachel Weber, Rod Karevan, Melissa C Larson, Honglin Song, Daniel C Tessier, François Bacot, Daniel Vincent, Julie M Cunningham, Joe Dennis, Ed Dicks, Australian Cancer Study, Australian Ovarian Cancer Study Group, Katja K Aben, Hoda Anton-Culver, Natalia Antonenkova, Sebastian M Armasu, Laura Baglietto, Elisa V Bandera, Matthias W Beckmann, Michael J Birrer, Greg Bloom, Natalia Bogdanova, James D Brenton, Louise A Brinton, Angela Brooks-Wilson, Robert Brown, Ralf Butzow, Ian Campbell, Michael E Carney, Renato S Carvalho, Jenny Chang-Claude, Y Anne Chen, Zhihua Chen, Wong-Ho Chow, Mine S Cicek, Gerhard Coetzee, Linda S Cook, Daniel W Cramer, Cezary Cybulski, Agnieszka Dansonka-Mieszkowska, Evelyn Despierre, Jennifer A Doherty, Thilo Dörk, Andreas du Bois, Matthias Dürst, Diana Eccles, Robert Edwards, Arif B Ekici, Peter A Fasching, David Fenstermacher, James Flanagan, Yu-Tang Gao, Montserrat Garcia-Closas, Aleksandra Gentry-Maharaj, Graham Giles, Anxhela Gjyshi, Martin Gore, Jacek Gronwald, Qi Guo, Mari K Halle, Philipp Harter, Alexander Hein, Florian Heitz, Peter Hillemanns, Maureen Hoatlin, Estrid Høgdall, Claus K Høgdall, Satoyo Hosono, Anna Jakubowska, Allan Jensen, Kimberly R Kalli, Beth Y Karlan, Linda E Kelemen, Lambertus A Kiemeney, Susanne Krüger Kjaer, Gottfried E Konecny, Camilla Krakstad, Jolanta Kupryjanczyk, Diether Lambrechts, Sandrina Lambrechts, Nhu D Le, Nathan Lee, Janet Lee, Arto Leminen, Boon Kiong Lim, Jolanta Lissowska, Jan Lubiński, Lene Lundvall, Galina Lurie, Leon F A G Massuger, Keitaro Matsuo, Valerie McGuire, John R McLaughlin, Usha Menon, Francesmary Modugno, Kirsten B Moysich, Toru Nakanishi, Steven A Narod, Roberta B Ness, Heli Nevanlinna, Stefan Nickels, Houtan Noushmehr, Kunle Odunsi, Sara Olson, Irene Orlow, James Paul, Tanja Pejovic, Liisa M Pelttari, Jenny Permuth-Wey, Malcolm C Pike, Elizabeth M Poole, Xiaotao Qu, Harvey A Risch, Lorna Rodriguez-Rodriguez, Mary Anne Rossing, Anja Rudolph, Ingo Runnebaum, Iwona K Rzepecka, Helga B Salvesen, Ira Schwaab, Gianluca Severi, Hui Shen, Vijayalakshmi Shridhar, Xiao-Ou Shu, Weiva Sieh, Melissa C Southey, Paul Spellman, Kazuo Tajima, Soo-Hwang Teo, Kathryn L Terry, Pamela J Thompson, Agnieszka Timorek, Shelley S Tworoger, Anne M van Altena, David van den Berg, Ignace Vergote, Robert A Vierkant, Allison F Vitonis, Shan Wang-Gohrke, Nicolas Wentzensen, Alice S Whittemore, Elisabeth Wik, Boris Winterhoff, Yin Ling Woo, Anna H Wu, Hannah P Yang, Wei Zheng, Argyrios Ziogas, Famida Zulkifli, Marc T Goodman, Per Hall, Douglas F Easton, Celeste L Pearce, Andrew Berchuck, Georgia Chenevix-Trench, Edwin Iversen, Alvaro N A Monteiro, Simon A Gayther, Joellen M Schildkraut, Thomas A Sellers

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. More... »

PAGES

362

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  • Journal

    TITLE

    Nature Genetics

    ISSUE

    4

    VOLUME

    45

    Author Affiliations

  • University of Cambridge
  • Moffitt Cancer Center
  • University of Southern California
  • Mayo Clinic
  • Duke University Hospital
  • McGill University and Génome Québec Innovation Centre
  • Radboud University Nijmegen Medical Centre
  • University of California, Irvine
  • University of Melbourne
  • Rutgers University
  • Massachusetts General Hospital
  • Hannover Medical School
  • Cancer Research UK Cambridge Institute
  • National Cancer Institute
  • BC Cancer Agency
  • Imperial College London
  • Helsinki University Central Hospital
  • University of Hawaii at Manoa
  • German Cancer Research Center
  • University of New Mexico
  • Harvard University
  • Pomeranian Medical University
  • Centrum Onkologii Instytut
  • Dartmouth College
  • Jena University Hospital
  • Magee-Womens Research Institute
  • University of Erlangen-Nuremberg
  • University of California Los Angeles
  • Shanghai Cancer Institute
  • Institute of Cancer Research
  • Monash University
  • Royal Marsden Hospital
  • University of Bergen
  • Oregon Health & Science University
  • University of Copenhagen
  • Rigshospitalet
  • Aichi Cancer Center
  • Danish Cancer Society
  • Cedars-Sinai Medical Center
  • University of Calgary
  • KU Leuven
  • Stanford University
  • Lunenfeld-Tanenbaum Research Institute
  • University of Pittsburgh
  • Roswell Park Cancer Institute
  • Okazaki City Hospital
  • University of Toronto
  • The University of Texas Health Science Center at Houston
  • Memorial Sloan Kettering Cancer Center
  • Beatson West of Scotland Cancer Centre
  • Brigham and Women's Hospital
  • Yale University
  • Fred Hutchinson Cancer Research Center
  • Vanderbilt University
  • Medical University of Warsaw
  • University of Ulm
  • QIMR Berghofer Medical Research Institute
  • Duke University
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/ng.2564

    DOI

    http://dx.doi.org/10.1038/ng.2564

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1006744695

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/23535730


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