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

Author

Listed:
  • Jennifer Permuth-Wey

    (Moffitt Cancer Center, Tampa)

  • Kate Lawrenson

    (Keck School of Medicine, University of Southern California Norris Comprehensive Cancer Center, Los Angeles)

  • Howard C. Shen

    (Keck School of Medicine, University of Southern California Norris Comprehensive Cancer Center, Los Angeles)

  • Aneliya Velkova

    (Moffitt Cancer Center, Tampa)

  • Jonathan P. Tyrer

    (University of Cambridge)

  • Zhihua Chen

    (Moffitt Cancer Center)

  • Hui-Yi Lin

    (Moffitt Cancer Center)

  • Y Ann Chen

    (Moffitt Cancer Center)

  • Ya-Yu Tsai

    (Moffitt Cancer Center, Tampa)

  • Xiaotao Qu

    (Moffitt Cancer Center)

  • Susan J. Ramus

    (Keck School of Medicine, University of Southern California Norris Comprehensive Cancer Center, Los Angeles)

  • Rod Karevan

    (Keck School of Medicine, University of Southern California Norris Comprehensive Cancer Center, Los Angeles)

  • Janet Lee

    (Keck School of Medicine, University of Southern California Norris Comprehensive Cancer Center, Los Angeles)

  • Nathan Lee

    (Keck School of Medicine, University of Southern California Norris Comprehensive Cancer Center, Los Angeles)

  • Melissa C. Larson

    (Mayo Clinic)

  • Katja K. Aben

    (Biostatistics and HTA, Radboud University Medical Centre
    Comprehensive Cancer Center The Netherlands)

  • Hoda Anton-Culver

    (Director of Genetic Epidemiology Research Institute, UCI Center of Medicine, University of California Irvine)

  • Natalia Antonenkova

    (Byelorussian Institute for Oncology and Medical Radiology Aleksandrov N.N.)

  • Antonis C. Antoniou

    (Centre for Cancer Genetic Epidemiology, University of Cambridge)

  • Sebastian M. Armasu

    (Mayo Clinic)

  • François Bacot

    (McGill University and Génome Québec Innovation Centre)

  • Laura Baglietto

    (Cancer Epidemiology Centre, The Cancer Council Victoria
    Centre for Molecular, Environmental, Genetic and Analytical Epidemiology, University of Melbourne)

  • Elisa V. Bandera

    (The Cancer Institute of New Jersey, Robert Wood Johnson Medical School)

  • Jill Barnholtz-Sloan

    (Case Comprehensive Cancer Center, Case Western Reserve University School of Medicine)

  • Matthias W. Beckmann

    (University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nuremberg, Comprehensive Cancer Center)

  • Michael J. Birrer

    (Massachusetts General Hospital)

  • Greg Bloom

    (Moffitt Cancer Center)

  • Natalia Bogdanova

    (Gynaecology Research Unit, Hannover Medical School)

  • Louise A. Brinton

    (National Cancer Institute)

  • Angela Brooks-Wilson

    (Genome Sciences Centre, BC Cancer Agency)

  • Robert Brown

    (Imperial College London)

  • Ralf Butzow

    (University of Helsinki and Helsinki University Central Hospital
    Helsinki University Central Hospital)

  • Qiuyin Cai

    (Vanderbilt Epidemiology Center and Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine)

  • Ian Campbell

    (Peter MacCallum Cancer Centre
    University of Melbourne)

  • Jenny Chang-Claude

    (German Cancer Research Center)

  • Stephen Chanock

    (National Cancer Institute)

  • Georgia Chenevix-Trench

    (Cancer Genetics Laboratory, Queensland Institute of Medical Research)

  • Jin Q. Cheng

    (Moffitt Cancer Center)

  • Mine S. Cicek

    (Mayo Clinic College of Medicine)

  • Gerhard A. Coetzee

    (Microbiology and Preventive Medicine, University of Southern California, Norris Comprehensive Cancer Center)

  • Linda S. Cook

    (University of New Mexico)

  • Fergus J. Couch

    (Mayo Clinic)

  • Daniel W. Cramer

    (Obstetrics and Gynecology Epidemiology Center, Brigham and Women's Hospital and Harvard Medical School)

  • Julie M. Cunningham

    (Mayo Clinic)

  • Agnieszka Dansonka-Mieszkowska

    (The Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology)

  • Evelyn Despierre

    (University Hospitals Leuven)

  • Jennifer A. Doherty

    (Section of Biostatistics and Epidemiology, The Geisel School of Medicine at Dartmouth)

  • Thilo Dörk

    (Gynaecology Research Unit, Hannover Medical School)

  • Andreas du Bois

    (Dr. Horst Schmidt Klinik Wiesbaden
    Kliniken Essen-Mitte)

  • Matthias Dürst

    (Jena University Hospital)

  • Douglas F. Easton

    (Centre for Cancer Genetic Epidemiology, University of Cambridge
    Centre for Cancer Genetic Epidemiology, University of Cambridge)

  • Diana Eccles

    (Faculty of Medicine, University of Southampton, University Hospital Southampton)

  • Robert Edwards

    (Maggee Women's Hospital)

  • Arif B. Ekici

    (Institute of Human Genetics, Friedrich-Alexander-University Erlangen-Nuremberg)

  • Peter A. Fasching

    (University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nuremberg, Comprehensive Cancer Center
    David Geffen School of Medicine, University of California at Los Angeles)

  • David A. Fenstermacher

    (Moffitt Cancer Center)

  • James M. Flanagan

    (Imperial College London)

  • Montserrat Garcia-Closas

    (Sections of Epidemiology and Genetics at the Institute of Cancer Research and Breakthrough Breast Cancer Research Centre)

  • Aleksandra Gentry-Maharaj

    (Gynaecological Cancer Research Centre, Women’s Cancer, Institute for Women's Health, University College London)

  • Graham G. Giles

    (Cancer Epidemiology Centre, The Cancer Council Victoria
    Centre for Molecular, Environmental, Genetic and Analytical Epidemiology, University of Melbourne
    Monash University)

  • Rosalind M. Glasspool

    (The Beatson West of Scotland Cancer Centre)

  • Jesus Gonzalez-Bosquet

    (Moffitt Cancer Center)

  • Marc T. Goodman

    (Samuel Oschin Comprehensive Cancer Institute, Cedars Sinai Medical Center)

  • Martin Gore

    (Gynecological Oncology Unit, The Royal Marsden Hospital)

  • Bohdan Górski

    (International Hereditary Cancer Center, Pomeranian Medical University)

  • Jacek Gronwald

    (International Hereditary Cancer Center, Pomeranian Medical University)

  • Per Hall

    (Karolinska Istitutet)

  • Mari K. Halle

    (Haukeland University Hospital
    University of Bergen)

  • Philipp Harter

    (Dr. Horst Schmidt Klinik Wiesbaden
    Kliniken Essen-Mitte)

  • Florian Heitz

    (Dr. Horst Schmidt Klinik Wiesbaden
    Kliniken Essen-Mitte)

  • Peter Hillemanns

    (Clinics of Obstetrics and Gynaecology, Hannover Medical School)

  • Maureen Hoatlin

    (Oregon Health and Science University)

  • Claus K. Høgdall

    (The Juliane Marie Centre)

  • Estrid Høgdall

    (Molecular Unit, Herlev Hospital, University of Copenhagen
    Virus, Lifestyle and Genes, Danish Cancer Society Research Center)

  • Satoyo Hosono

    (Aichi Cancer Center Research Institute)

  • Anna Jakubowska

    (International Hereditary Cancer Center, Pomeranian Medical University)

  • Allan Jensen

    (Virus, Lifestyle and Genes, Danish Cancer Society Research Center)

  • Heather Jim

    (Moffitt Cancer Center)

  • Kimberly R. Kalli

    (Mayo Clinic)

  • Beth Y. Karlan

    (Women’s Cancer Program at the Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center)

  • Stanley B. Kaye

    (Section of Medicine, Institute of Cancer Research)

  • Linda E. Kelemen

    (Alberta Health Services-Cancer Care, Calgary, Alberta, University of Calgary)

  • Lambertus A. Kiemeney

    (Biostatistics and HTA, Radboud University Medical Centre
    Comprehensive Cancer Center The Netherlands
    Radboud University Medical Centre)

  • Fumitaka Kikkawa

    (Nagoya University Graduate School of Medicine)

  • Gottfried E. Konecny

    (David Geffen School of Medicine, University of California at Los Angeles)

  • Camilla Krakstad

    (Haukeland University Hospital
    University of Bergen)

  • Susanne Krüger Kjaer

    (The Juliane Marie Centre
    Virus, Lifestyle and Genes, Danish Cancer Society Research Center)

  • Jolanta Kupryjanczyk

    (The Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology)

  • Diether Lambrechts

    (Vesalius Research Center, VIB
    Laboratory for Translational Genetics, University of Leuven)

  • Sandrina Lambrechts

    (University Hospitals Leuven)

  • Johnathan M. Lancaster

    (Moffitt Cancer Center)

  • Nhu D. Le

    (Cancer Control Research, BC Cancer Agency)

  • Arto Leminen

    (University of Helsinki and Helsinki University Central Hospital)

  • Douglas A. Levine

    (Gynecology Service, Memorial Sloan-Kettering Cancer Center)

  • Dong Liang

    (College of Pharmacy and Health Sciences, Texas Southern University)

  • Boon Kiong Lim

    (Affiliated to UM Cancer Research Institute, Faculty of Medicine, University Malaya)

  • Jie Lin

    (The University of Texas MD Anderson Cancer Center)

  • Jolanta Lissowska

    (The Maria Sklodowska-Curie Memorial Cancer Center)

  • Karen H. Lu

    (The University of Texas MD Anderson Cancer Center)

  • Jan Lubiński

    (International Hereditary Cancer Center, Pomeranian Medical University)

  • Galina Lurie

    (Cancer Epidemiology Program, University of Hawaii Cancer Center)

  • Leon F.A.G Massuger

    (Radboud University Medical Centre)

  • Keitaro Matsuo

    (Aichi Cancer Center Research Institute)

  • Valerie McGuire

    (Stanford University School of Medicine)

  • John R. McLaughlin

    (Dalla Lana School of Public Health, Faculty of Medicine, University of Toronto
    Samuel Lunenfeld Research Institute, Mount Sinai Hospital)

  • Usha Menon

    (Gynaecological Cancer Research Centre, Women’s Cancer, Institute for Women's Health, University College London)

  • Francesmary Modugno

    (Womens Cancer Research Program, Magee-Womens Research Institute and University of Pittsburgh Cancer Institute
    University of Pittsburgh Graduate School of Public Health
    Gynecology and Reproductive Sciences, University of Pittsburgh School of Medicine)

  • Kirsten B. Moysich

    (Roswell Park Cancer Institute)

  • Toru Nakanishi

    (Aichi Cancer Center Central Hospital)

  • Steven A. Narod

    (Women’s College Research Institute, University of Toronto)

  • Lotte Nedergaard

    (Rigshospitalet, University of Copenhagen)

  • Roberta B. Ness

    (The University of Texas School of Public Health)

  • Heli Nevanlinna

    (Helsinki University Central Hospital)

  • Stefan Nickels

    (German Cancer Research Center)

  • Houtan Noushmehr

    (Microbiology and Preventive Medicine, University of Southern California, Norris Comprehensive Cancer Center
    USC Epigenome Center, Keck School of Medicine, University of Southern California, Norris Comprehensive Cancer Center
    Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo)

  • Kunle Odunsi

    (Roswell Park Cancer Institute)

  • Sara H. Olson

    (Memorial Sloan-Kettering Cancer Center)

  • Irene Orlow

    (Memorial Sloan-Kettering Cancer Center)

  • James Paul

    (The Beatson West of Scotland Cancer Centre)

  • Celeste L. Pearce

    (Keck School of Medicine, University of Southern California Norris Comprehensive Cancer Center, Los Angeles)

  • Tanja Pejovic

    (Oregon Health and Science University
    Knight Cancer Institute, Oregon Health and Science University)

  • Liisa M. Pelttari

    (Helsinki University Central Hospital)

  • Malcolm C. Pike

    (Keck School of Medicine, University of Southern California Norris Comprehensive Cancer Center, Los Angeles
    Memorial Sloan-Kettering Cancer Center)

  • Elizabeth M. Poole

    (Harvard Medical School and Brigham and Women’s Hospital
    Harvard School of Public Health)

  • Paola Raska

    (Case Comprehensive Cancer Center, Case Western Reserve University School of Medicine)

  • Stefan P. Renner

    (University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nuremberg, Comprehensive Cancer Center)

  • Harvey A. Risch

    (Yale University School of Public Health and School of Medicine)

  • Lorna Rodriguez-Rodriguez

    (The Cancer Institute of New Jersey, Robert Wood Johnson Medical School)

  • Mary Anne Rossing

    (Program in Epidemiology, Fred Hutchinson Cancer Research Center
    University of Washington)

  • Anja Rudolph

    (German Cancer Research Center)

  • Ingo B. Runnebaum

    (Jena University Hospital)

  • Iwona K. Rzepecka

    (The Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology)

  • Helga B. Salvesen

    (Haukeland University Hospital
    University of Bergen)

  • Ira Schwaab

    (Institut für Humangenetik Wiesbaden)

  • Gianluca Severi

    (Cancer Epidemiology Centre, The Cancer Council Victoria
    Centre for Molecular, Environmental, Genetic and Analytical Epidemiology, University of Melbourne)

  • Viji Shridhar

    (Mayo Clinic)

  • Xiao-Ou Shu

    (Vanderbilt Epidemiology Center and Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine)

  • Yurii B. Shvetsov

    (Cancer Epidemiology Program, University of Hawaii Cancer Center)

  • Weiva Sieh

    (Stanford University School of Medicine)

  • Honglin Song

    (University of Cambridge)

  • Melissa C. Southey

    (Genetic Epidemiology Laboratory, The University of Melbourne)

  • Beata Spiewankiewicz

    (The Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology)

  • Daniel Stram

    (Keck School of Medicine, University of Southern California Norris Comprehensive Cancer Center, Los Angeles)

  • Rebecca Sutphen

    (Pediatrics Epidemiology Center, College of Medicine, University of South Florida)

  • Soo-Hwang Teo

    (Cancer Research Initiatives Foundation, Sime Darby Medical Centre
    Faculty of Medicine, University Malaya)

  • Kathryn L. Terry

    (Obstetrics and Gynecology Epidemiology Center, Brigham and Women's Hospital and Harvard Medical School)

  • Daniel C. Tessier

    (McGill University and Génome Québec Innovation Centre)

  • Pamela J. Thompson

    (Samuel Oschin Comprehensive Cancer Institute, Cedars Sinai Medical Center)

  • Shelley S. Tworoger

    (Harvard Medical School and Brigham and Women’s Hospital
    Harvard School of Public Health)

  • Anne M. van Altena

    (Radboud University Medical Centre)

  • Ignace Vergote

    (University Hospitals Leuven)

  • Robert A. Vierkant

    (Mayo Clinic)

  • Daniel Vincent

    (McGill University and Génome Québec Innovation Centre)

  • Allison F. Vitonis

    (Obstetrics and Gynecology Epidemiology Center, Brigham and Women's Hospital and Harvard Medical School)

  • Shan Wang-Gohrke

    (University of Ulm)

  • Rachel Palmieri Weber

    (Duke University Medical Center)

  • Nicolas Wentzensen

    (National Cancer Institute)

  • Alice S. Whittemore

    (Stanford University School of Medicine)

  • Elisabeth Wik

    (Haukeland University Hospital
    University of Bergen)

  • Lynne R. Wilkens

    (Cancer Epidemiology Program, University of Hawaii Cancer Center)

  • Boris Winterhoff

    (Mayo Clinic)

  • Yin Ling Woo

    (Affiliated to UM Cancer Research Institute, Faculty of Medicine, University Malaya)

  • Anna H. Wu

    (Keck School of Medicine, University of Southern California Norris Comprehensive Cancer Center, Los Angeles)

  • Yong-Bing Xiang

    (Shanghai Cancer Institute)

  • Hannah P. Yang

    (National Cancer Institute)

  • Wei Zheng

    (Vanderbilt Epidemiology Center and Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine)

  • Argyrios Ziogas

    (Center for Cancer Genetics Research and Prevention, School of Medicine, University of California Irvine)

  • Famida Zulkifli

    (Cancer Research Initiatives Foundation, Sime Darby Medical Centre
    Faculty of Medicine, University Malaya)

  • Catherine M. Phelan

    (Moffitt Cancer Center, Tampa)

  • Edwin Iversen

    (Duke University)

  • Joellen M. Schildkraut

    (Duke University Medical Center
    Cancer Prevention, Detection and Control Research Program, Duke Cancer Institute)

  • Andrew Berchuck

    (Duke Cancer Institute)

  • Brooke L. Fridley

    (University of Kansas Medical Center)

  • Ellen L. Goode

    (Mayo Clinic College of Medicine)

  • Paul D.P. Pharoah

    (Centre for Cancer Genetic Epidemiology, University of Cambridge
    Jena University Hospital)

  • Alvaro N.A. Monteiro

    (Moffitt Cancer Center, Tampa)

  • Thomas A. Sellers

    (Moffitt Cancer Center, Tampa)

  • Simon A. Gayther

    (Keck School of Medicine, University of Southern California Norris Comprehensive Cancer Center, Los Angeles)

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 an inversion polymorphism at 17q21.31. Additional genotyping of non-miRSNPs at 17q21.31 reveals stronger signals outside the inversion (P=10−10). Variation at 17q21.31 is associated with neurological diseases, and our collaboration is the first to report an association with EOC susceptibility. An integrated molecular analysis in this region provides evidence for ARHGAP27 and PLEKHM1 as candidate EOC susceptibility genes.

Suggested Citation

  • 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 Le, 2013. "Identification and molecular characterization of a new ovarian cancer susceptibility locus at 17q21.31," Nature Communications, Nature, vol. 4(1), pages 1-12, June.
    • Handle: RePEc:nat:natcom:v:4:y:2013:i:1:d:10.1038_ncomms2613
    DOI: 10.1038/ncomms2613
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