Genome-wide significant risk associations for mucinous ovarian carcinoma View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2015-08

AUTHORS

Linda E. Kelemen, Kate Lawrenson, Jonathan Tyrer, Qiyuan Li, Janet M. Lee, Ji-Heui Seo, Catherine M. Phelan, Jonathan Beesley, Xiaoqin Chen, Tassja J. Spindler, Katja K.H. Aben, Hoda Anton-Culver, Natalia Antonenkova, , , Helen Baker, Elisa V. Bandera, Yukie Bean, Matthias W. Beckmann, Maria Bisogna, Line Bjorge, Natalia Bogdanova, Louise A. Brinton, Angela Brooks-Wilson, Fiona Bruinsma, Ralf Butzow, Ian G. Campbell, Karen Carty, Jenny Chang-Claude, Y. Ann Chen, Zhihua Chen, Linda S. Cook, Daniel W. Cramer, Julie M. Cunningham, Cezary Cybulski, Agnieszka Dansonka-Mieszkowska, Joe Dennis, Ed Dicks, Jennifer A. Doherty, Thilo Dörk, Andreas du Bois, Matthias Dürst, Diana Eccles, Douglas T. Easton, Robert P. Edwards, Ursula Eilber, Arif B. Ekici, Svend Aage Engelholm, Peter A. Fasching, Brooke L. Fridley, Yu-Tang Gao, Aleksandra Gentry-Maharaj, Graham G. Giles, Rosalind Glasspool, Ellen L. Goode, Marc T. Goodman, Jacek Grownwald, Patricia Harrington, Philipp Harter, Hanis Nazihah Hasmad, Alexander Hein, Florian Heitz, Michelle A.T. Hildebrandt, Peter Hillemanns, Estrid Hogdall, Claus Hogdall, Satoyo Hosono, Edwin S. Iversen, Anna Jakubowska, Allan Jensen, Bu-Tian Ji, Beth Y Karlan, Melissa Kellar, Joseph L. Kelley, Lambertus A. Kiemeney, Camilla Krakstad, Susanne K. Kjaer, Jolanta Kupryjanczyk, Diether Lambrechts, Sandrina Lambrechts, Nhu D. Le, Alice W. Lee, Shashi Lele, Arto Leminen, Jenny Lester, Douglas A. Levine, Dong Liang, Jolanta Lissowska, Karen Lu, Jan Lubinski, Lene Lundvall, Leon F.A.G. Massuger, Keitaro Matsuo, Valerie McGuire, John R. McLaughlin, Iain McNeish, Usha Menon, Francesmary Modugno, Joanna Moes-Sosnowska, Kirsten B. Moysich, Steven A. Narod, Lotte Nedergaard, Roberta B. Ness, Heli Nevanlinna, Mat Adenan Noor Azmi, Kunle Odunsi, Sara H. Olson, Irene Orlow, Sandra Orsulic, Rachel Palmieri Weber, James Paul, Celeste Leigh Pearce, Tanja Pejovic, Liisa M. Pelttari, Jennifer Permuth-Wey, Malcolm C. Pike, Elizabeth M. Poole, Susan J. Ramus, Harvey A. Risch, Barry Rosen, Mary Anne Rossing, Joseph H. Rothstein, Anja Rudolph, Ingo B. Runnebaum, Iwona K. Rzepecka, Helga B. Salvesen, Joellen M. Schildkraut, Ira Schwaab, Xiao-Ou Shu, Yurii B Shvetsov, Nadeem Siddiqui, Weiva Sieh, Honglin Song, Melissa C. Southey, Lara Sucheston, Ingvild L. Tangen, Soo-Hwang Teo, Kathryn L. Terry, Pamela J Thompson, Shelley S. Tworoger, Anne M. van Altena, Els Van Nieuwenhuysen, Ignace Vergote, Robert A. Vierkant, Shan Wang-Gohrke, Christine Walsh, Nicolas Wentzensen, Alice S. Whittemore, Kristine G. Wicklund, Lynne R. Wilkens, Sawicki Wlodzimierz, Yin-Ling Woo, Xifeng Wu, Anna H. Wu, Hannah Yang, Wei Zheng, Argyrios Ziogas, Thomas A. Sellers, Matthew L. Freedman, Georgia Chenevix-Trench, Paul D. Pharoah, Simon A. Gayther, Andrew Berchuck

ABSTRACT

Genome-wide association studies have identified several risk associations for ovarian carcinomas but not for mucinous ovarian carcinomas (MOCs). Our analysis of 1,644 MOC cases and 21,693 controls with imputation identified 3 new risk associations: rs752590 at 2q13 (P = 3.3 × 10(-8)), rs711830 at 2q31.1 (P = 7.5 × 10(-12)) and rs688187 at 19q13.2 (P = 6.8 × 10(-13)). We identified significant expression quantitative trait locus (eQTL) associations for HOXD9 at 2q31.1 in ovarian (P = 4.95 × 10(-4), false discovery rate (FDR) = 0.003) and colorectal (P = 0.01, FDR = 0.09) tumors and for PAX8 at 2q13 in colorectal tumors (P = 0.03, FDR = 0.09). Chromosome conformation capture analysis identified interactions between the HOXD9 promoter and risk-associated SNPs at 2q31.1. Overexpressing HOXD9 in MOC cells augmented the neoplastic phenotype. These findings provide the first evidence for MOC susceptibility variants and insights into the underlying biology of the disease. More... »

PAGES

888-897

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  • Journal

    TITLE

    Nature Genetics

    ISSUE

    8

    VOLUME

    47

    Author Affiliations

  • Medical University of South Carolina
  • University of Southern California
  • University of Cambridge
  • Dana–Farber Cancer Institute
  • Moffitt Cancer Center
  • QIMR Berghofer Medical Research Institute
  • Radboud University Nijmegen Medical Centre
  • University of California, Irvine
  • Rutgers University
  • Oregon Health & Science University
  • Memorial Sloan Kettering Cancer Center
  • University of Bergen
  • Hannover Medical School
  • National Cancer Institute
  • Simon Fraser University
  • Cancer Council Victoria
  • Helsinki University Central Hospital
  • University of Melbourne
  • Beatson West of Scotland Cancer Centre
  • German Cancer Research Center
  • University of New Mexico
  • Brigham and Women's Hospital
  • Mayo Clinic
  • Pomeranian Medical University
  • Centrum Onkologii Instytut
  • Dartmouth College
  • Friedrich Schiller University Jena
  • University of Southampton
  • University of Pittsburgh
  • University of Erlangen-Nuremberg
  • University of California Los Angeles
  • University of Kansas Medical Center
  • Shanghai Cancer Institute
  • University College London
  • Monash University
  • Cedars-Sinai Medical Center
  • The University of Texas MD Anderson Cancer Center
  • University of Copenhagen
  • Aichi Cancer Center
  • Duke University
  • KU Leuven
  • Universitaire Ziekenhuizen Leuven
  • BC Cancer Agency
  • Roswell Park Cancer Institute
  • Texas Southern University
  • Kyushu University
  • Stanford University
  • Public Health Ontario
  • University of Glasgow
  • University of Pittsburgh Cancer Institute
  • University of Toronto
  • The University of Texas Health Science Center at Houston
  • Duke University Hospital
  • University of Michigan–Ann Arbor
  • Yale University
  • University of Washington
  • Praxis für Humangenetik
  • Vanderbilt University
  • University of Hawaii at Manoa
  • Glasgow Royal Infirmary
  • University of Ulm
  • Fred Hutchinson Cancer Research Center
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/ng.3336

    DOI

    http://dx.doi.org/10.1038/ng.3336

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1004740231

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/26075790


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