Identification and molecular characterization of a new ovarian cancer susceptibility locus at 17q21.31
Identifieur interne : 000B53 ( Pmc/Corpus ); précédent : 000B52; suivant : 000B54Identification and molecular characterization of a new ovarian cancer susceptibility locus at 17q21.31
Auteurs : 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 Antoniou ; Sebastian M. Armasu ; François Bacot ; Laura Baglietto ; Elisa V. Bandera ; Jill Barnholtz-Sloan ; Matthias W. Beckmann ; Michael J. Birrer ; Greg Bloom ; Natalia Bogdanova ; Louise A. Brinton ; Angela Brooks-Wilson ; Robert Brown ; Ralf Butzow ; Qiuyin Cai ; Ian Campbell ; Jenny Chang-Claude ; Stephen Chanock ; Georgia Chenevix-Trench ; Jin Q. Cheng ; Mine S. Cicek ; Gerhard A. Coetzee ; Linda S. Cook ; Fergus J. Couch ; Daniel W. Cramer ; Julie M. Cunningham ; Agnieszka Dansonka-Mieszkowska ; Evelyn Despierre ; Jennifer A. Doherty ; Thilo Dörk ; Andreas Du Bois ; Matthias Dürst ; Douglas F. Easton ; Diana Eccles ; Robert Edwards ; Arif B. Ekici ; Peter A. Fasching ; David A. Fenstermacher ; James M. Flanagan ; Montserrat Garcia-Closas ; Aleksandra Gentry-Maharaj ; Graham G. Giles ; Rosalind M. Glasspool ; Jesus Gonzalez-Bosquet ; Marc T. Goodman ; Martin Gore ; Bohdan G Rski ; Jacek Gronwald ; Per Hall ; Mari K. Halle ; Philipp Harter ; Florian Heitz ; Peter Hillemanns ; Maureen Hoatlin ; Claus K. H Gdall ; Estrid H Gdall ; Satoyo Hosono ; Anna Jakubowska ; Allan Jensen ; Heather Jim ; Kimberly R. Kalli ; Beth Y. Karlan ; Stanley B. Kaye ; Linda E. Kelemen ; Lambertus A. Kiemeney ; Fumitaka Kikkawa ; Gottfried E. Konecny ; Camilla Krakstad ; Susanne Krüger Kjaer ; Jolanta Kupryjanczyk ; Diether Lambrechts ; Sandrina Lambrechts ; Johnathan M. Lancaster ; Nhu D. Le ; Arto Leminen ; Douglas A. Levine ; Dong Liang ; Boon Kiong Lim ; Jie Lin ; Jolanta Lissowska ; Karen H. Lu ; Jan Lubi Ski ; 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 ; Lotte Nedergaard ; Roberta B. Ness ; Heli Nevanlinna ; Stefan Nickels ; Houtan Noushmehr ; Kunle Odunsi ; Sara H. Olson ; Irene Orlow ; James Paul ; Celeste L. Pearce ; Tanja Pejovic ; Liisa M. Pelttari ; Malcolm C. Pike ; Elizabeth M. Poole ; Paola Raska ; Stefan P. Renner ; Harvey A. Risch ; Lorna Rodriguez-Rodriguez ; Mary Anne Rossing ; Anja Rudolph ; Ingo B. Runnebaum ; Iwona K. Rzepecka ; Helga B. Salvesen ; Ira Schwaab ; Gianluca Severi ; Vijayalakshmi Shridhar ; Xiao-Ou Shu ; Yurii B. Shvetsov ; Weiva Sieh ; Honglin Song ; Melissa C. Southey ; Beata Spiewankiewicz ; Daniel Stram ; Rebecca Sutphen ; Soo-Hwang Teo ; Kathryn L. Terry ; Daniel C. Tessier ; Pamela J. Thompson ; Shelley S. Tworoger ; Anne M. Van Altena ; Ignace Vergote ; Robert A. Vierkant ; Daniel Vincent ; Allison F. Vitonis ; Shan Wang-Gohrke ; Rachel Palmieri Weber ; Nicolas Wentzensen ; Alice S. Whittemore ; Elisabeth Wik ; Lynne R. Wilkens ; Boris Winterhoff ; Yin Ling Woo ; Anna H. Wu ; Yong-Bing Xiang ; Hannah P. Yang ; Wei Zheng ; Argyrios Ziogas ; Famida Zulkifli ; Catherine M. Phelan ; Edwin Iversen ; Joellen M. Schildkraut ; Andrew Berchuck ; Brooke L. Fridley ; Ellen L. Goode ; Paul D. P. Pharoah ; Alvaro N. A. Monteiro ; Thomas A. Sellers ; Simon A. GaytherSource :
- Nature communications [ 2041-1723 ] ; 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 binding site 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 (OR=1.12,
Url:
DOI: 10.1038/ncomms2613
PubMed: 23535648
PubMed Central: 3709460
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PMC:3709460Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Identification and molecular characterization of a new ovarian cancer susceptibility locus at 17q21.31</title><author><name sortKey="Permuth Wey, Jennifer" sort="Permuth Wey, Jennifer" uniqKey="Permuth Wey J" first="Jennifer" last="Permuth-Wey">Jennifer Permuth-Wey</name><affiliation><nlm:aff id="A1">Department of Cancer Epidemiology, Division of Population Sciences, Moffitt Cancer Center, Tampa, FL, USA, 33612</nlm:aff></affiliation></author><author><name sortKey="Lawrenson, Kate" sort="Lawrenson, Kate" uniqKey="Lawrenson K" first="Kate" last="Lawrenson">Kate Lawrenson</name><affiliation><nlm:aff id="A2">Department of Preventive Medicine, Keck School of Medicine, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA, USA, 90033</nlm:aff></affiliation></author><author><name sortKey="Shen, Howard C" sort="Shen, Howard C" uniqKey="Shen H" first="Howard C." last="Shen">Howard C. Shen</name><affiliation><nlm:aff id="A2">Department of Preventive Medicine, Keck School of Medicine, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA, USA, 90033</nlm:aff></affiliation></author><author><name sortKey="Velkova, Aneliya" sort="Velkova, Aneliya" uniqKey="Velkova A" first="Aneliya" last="Velkova">Aneliya Velkova</name><affiliation><nlm:aff id="A1">Department of Cancer Epidemiology, Division of Population Sciences, Moffitt Cancer Center, Tampa, FL, USA, 33612</nlm:aff></affiliation></author><author><name sortKey="Tyrer, Jonathan P" sort="Tyrer, Jonathan P" uniqKey="Tyrer J" first="Jonathan P." last="Tyrer">Jonathan P. Tyrer</name><affiliation><nlm:aff id="A3">Department of Oncology, University of Cambridge, Cambridge, CB1 8RN, UK</nlm:aff></affiliation></author><author><name sortKey="Chen, Zhihua" sort="Chen, Zhihua" uniqKey="Chen Z" first="Zhihua" last="Chen">Zhihua Chen</name><affiliation><nlm:aff id="A4">Department of Biomedical Informatics, Moffitt Cancer Center, Tampa, FL, USA, 33612</nlm:aff></affiliation></author><author><name sortKey="Lin, Hui Yi" sort="Lin, Hui Yi" uniqKey="Lin H" first="Hui-Yi" last="Lin">Hui-Yi Lin</name><affiliation><nlm:aff id="A5">Department of Biostatistics, Moffitt Cancer Center, Tampa, FL, USA, 33612</nlm:aff></affiliation></author><author><name sortKey="Chen, Y Ann" sort="Chen, Y Ann" uniqKey="Chen Y" first="Y. Ann" last="Chen">Y. Ann Chen</name><affiliation><nlm:aff id="A5">Department of Biostatistics, Moffitt Cancer Center, Tampa, FL, USA, 33612</nlm:aff></affiliation></author><author><name sortKey="Tsai, Ya Yu" sort="Tsai, Ya Yu" uniqKey="Tsai Y" first="Ya-Yu" last="Tsai">Ya-Yu Tsai</name><affiliation><nlm:aff id="A1">Department of Cancer Epidemiology, Division of Population Sciences, Moffitt Cancer Center, Tampa, FL, USA, 33612</nlm:aff></affiliation></author><author><name sortKey="Qu, Xiaotao" sort="Qu, Xiaotao" uniqKey="Qu X" first="Xiaotao" last="Qu">Xiaotao Qu</name><affiliation><nlm:aff id="A4">Department of Biomedical Informatics, Moffitt Cancer Center, Tampa, FL, USA, 33612</nlm:aff></affiliation></author><author><name sortKey="Ramus, Susan J" sort="Ramus, Susan J" uniqKey="Ramus S" first="Susan J." last="Ramus">Susan J. Ramus</name><affiliation><nlm:aff id="A2">Department of Preventive Medicine, Keck School of Medicine, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA, USA, 90033</nlm:aff></affiliation></author><author><name sortKey="Karevan, Rod" sort="Karevan, Rod" uniqKey="Karevan R" first="Rod" last="Karevan">Rod Karevan</name><affiliation><nlm:aff id="A2">Department of Preventive Medicine, Keck School of Medicine, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA, USA, 90033</nlm:aff></affiliation></author><author><name sortKey="Lee, Janet" sort="Lee, Janet" uniqKey="Lee J" first="Janet" last="Lee">Janet Lee</name><affiliation><nlm:aff id="A2">Department of Preventive Medicine, Keck School of Medicine, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA, USA, 90033</nlm:aff></affiliation></author><author><name sortKey="Lee, Nathan" sort="Lee, Nathan" uniqKey="Lee N" first="Nathan" last="Lee">Nathan Lee</name><affiliation><nlm:aff id="A2">Department of Preventive Medicine, Keck School of Medicine, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA, USA, 90033</nlm:aff></affiliation></author><author><name sortKey="Larson, Melissa C" sort="Larson, Melissa C" uniqKey="Larson M" first="Melissa C." last="Larson">Melissa C. Larson</name><affiliation><nlm:aff id="A6">Department of Health Science Research, Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN, USA, 55905</nlm:aff></affiliation></author><author><name sortKey="Aben, Katja K" sort="Aben, Katja K" uniqKey="Aben K" first="Katja K." last="Aben">Katja K. Aben</name><affiliation><nlm:aff id="A7">Department of Epidemiology, Biostatistics and HTA, Radboud University Medical Centre, Nijmegen, HB 6500, Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A8">Comprehensive Cancer Center, the Netherlands, Utrecht, Amsterdam, 1066CX, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Anton Culver, Hoda" sort="Anton Culver, Hoda" uniqKey="Anton Culver H" first="Hoda" last="Anton-Culver">Hoda Anton-Culver</name><affiliation><nlm:aff id="A9">Department of Epidemiology, Director of Genetic Epidemiology Research Institute, UCI Center of Medicine, University of California Irvine, Irvine, CA, USA, 92697</nlm:aff></affiliation></author><author><name sortKey="Antonenkova, Natalia" sort="Antonenkova, Natalia" uniqKey="Antonenkova N" first="Natalia" last="Antonenkova">Natalia Antonenkova</name><affiliation><nlm:aff id="A10">Byelorussian Institute for Oncology and Medical Radiology Aleksandrov N.N., 223040, Minsk, Belarus</nlm:aff></affiliation></author><author><name sortKey="Antoniou, Antonis" sort="Antoniou, Antonis" uniqKey="Antoniou A" first="Antonis" last="Antoniou">Antonis Antoniou</name><affiliation><nlm:aff id="A11">Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, CB1 8RN, UK</nlm:aff></affiliation></author><author><name sortKey="Armasu, Sebastian M" sort="Armasu, Sebastian M" uniqKey="Armasu S" first="Sebastian M." last="Armasu">Sebastian M. Armasu</name><affiliation><nlm:aff id="A6">Department of Health Science Research, Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN, USA, 55905</nlm:aff></affiliation></author><author><name sortKey="Bacot, Francois" sort="Bacot, Francois" uniqKey="Bacot F" first="François" last="Bacot">François Bacot</name><affiliation><nlm:aff id="A14">McGill University and Génome Québec Innovation Centre, Montréal (Québec) Canada, H3A 0G1</nlm:aff></affiliation></author><author><name sortKey="Baglietto, Laura" sort="Baglietto, Laura" uniqKey="Baglietto L" first="Laura" last="Baglietto">Laura Baglietto</name><affiliation><nlm:aff id="A15">Cancer Epidemiology Centre, The Cancer Council Victoria, Melbourne, Carlton VIC 3053, Australia</nlm:aff></affiliation><affiliation><nlm:aff id="A16">Centre for Molecular, Environmental, Genetic and Analytical Epidemiology, University of Melbourne, Melbourne, VIC 3010, Australia</nlm:aff></affiliation></author><author><name sortKey="Bandera, Elisa V" sort="Bandera, Elisa V" uniqKey="Bandera E" first="Elisa V." last="Bandera">Elisa V. Bandera</name><affiliation><nlm:aff id="A17">The Cancer Institute of New Jersey, Robert Wood Johnson Medical School, New Brunswick, NJ, USA, 08901</nlm:aff></affiliation></author><author><name sortKey="Barnholtz Sloan, Jill" sort="Barnholtz Sloan, Jill" uniqKey="Barnholtz Sloan J" first="Jill" last="Barnholtz-Sloan">Jill Barnholtz-Sloan</name><affiliation><nlm:aff id="A18">Case Comprehensive Cancer Center, Case Western Reserve University School of Medicine, Cleveland, OH, USA, 44195</nlm:aff></affiliation></author><author><name sortKey="Beckmann, Matthias W" sort="Beckmann, Matthias W" uniqKey="Beckmann M" first="Matthias W." last="Beckmann">Matthias W. Beckmann</name><affiliation><nlm:aff id="A19">University Hospital Erlangen, Department of Gynecology and Obstetrics, Friedrich-Alexander-University Erlangen-Nuremberg, Comprehensive Cancer Center, Erlangen, 91054, Germany</nlm:aff></affiliation></author><author><name sortKey="Birrer, Michael J" sort="Birrer, Michael J" uniqKey="Birrer M" first="Michael J." last="Birrer">Michael J. Birrer</name><affiliation><nlm:aff id="A20">Massachusetts General Hospital, Boston, MA, USA, 02114</nlm:aff></affiliation></author><author><name sortKey="Bloom, Greg" sort="Bloom, Greg" uniqKey="Bloom G" first="Greg" last="Bloom">Greg Bloom</name><affiliation><nlm:aff id="A4">Department of Biomedical Informatics, Moffitt Cancer Center, Tampa, FL, USA, 33612</nlm:aff></affiliation></author><author><name sortKey="Bogdanova, Natalia" sort="Bogdanova, Natalia" uniqKey="Bogdanova N" first="Natalia" last="Bogdanova">Natalia Bogdanova</name><affiliation><nlm:aff id="A21">Gynaecology Research Unit, Hannover Medical School, Hannover, 30625, Germany</nlm:aff></affiliation></author><author><name sortKey="Brinton, Louise A" sort="Brinton, Louise A" uniqKey="Brinton L" first="Louise A." last="Brinton">Louise A. Brinton</name><affiliation><nlm:aff id="A22">Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda MD, USA, 20892</nlm:aff></affiliation></author><author><name sortKey="Brooks Wilson, Angela" sort="Brooks Wilson, Angela" uniqKey="Brooks Wilson A" first="Angela" last="Brooks-Wilson">Angela Brooks-Wilson</name><affiliation><nlm:aff id="A23">Genome Sciences Centre, BC Cancer Agency, Vancouver, BC, Canada, V5Z 1L3</nlm:aff></affiliation></author><author><name sortKey="Brown, Robert" sort="Brown, Robert" uniqKey="Brown R" first="Robert" last="Brown">Robert Brown</name><affiliation><nlm:aff id="A24">Department of Surgery and Cancer, Imperial College London, London, SW7 2AZ, UK</nlm:aff></affiliation></author><author><name sortKey="Butzow, Ralf" sort="Butzow, Ralf" uniqKey="Butzow R" first="Ralf" last="Butzow">Ralf Butzow</name><affiliation><nlm:aff id="A25">Department of Pathology, Helsinki University Central Hospital, Helsinki, Finland, 00530</nlm:aff></affiliation><affiliation><nlm:aff id="A26">Department of Obstetrics and Gynecology, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland, 00530</nlm:aff></affiliation></author><author><name sortKey="Cai, Qiuyin" sort="Cai, Qiuyin" uniqKey="Cai Q" first="Qiuyin" last="Cai">Qiuyin Cai</name><affiliation><nlm:aff id="A27">Vanderbilt Epidemiology Center and Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN, USA, 37232</nlm:aff></affiliation></author><author><name sortKey="Campbell, Ian" sort="Campbell, Ian" uniqKey="Campbell I" first="Ian" last="Campbell">Ian Campbell</name><affiliation><nlm:aff id="A13">Cancer Genetics Laboratory, Research Division, Peter MacCallum Cancer Centre, Melbourne, VIC 3002, Australia</nlm:aff></affiliation><affiliation><nlm:aff id="A28">Department of Pathology, University of Melbourne, Parkville, VIC 3053, Australia</nlm:aff></affiliation></author><author><name sortKey="Chang Claude, Jenny" sort="Chang Claude, Jenny" uniqKey="Chang Claude J" first="Jenny" last="Chang-Claude">Jenny Chang-Claude</name><affiliation><nlm:aff id="A29">German Cancer Research Center, Division of Cancer Epidemiology, 69120, Heidelberg, Germany</nlm:aff></affiliation></author><author><name sortKey="Chanock, Stephen" sort="Chanock, Stephen" uniqKey="Chanock S" first="Stephen" last="Chanock">Stephen Chanock</name><affiliation><nlm:aff id="A22">Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda MD, USA, 20892</nlm:aff></affiliation></author><author><name sortKey="Chenevix Trench, Georgia" sort="Chenevix Trench, Georgia" uniqKey="Chenevix Trench G" first="Georgia" last="Chenevix-Trench">Georgia Chenevix-Trench</name><affiliation><nlm:aff id="A12">Queensland Institute of Medical Research, Brisbane QLD 4006, Australia</nlm:aff></affiliation></author><author><name sortKey="Cheng, Jin Q" sort="Cheng, Jin Q" uniqKey="Cheng J" first="Jin Q." last="Cheng">Jin Q. Cheng</name><affiliation><nlm:aff id="A30">Department of Interdisciplinary Oncology, Moffitt Cancer Center, Tampa, FL, USA, 33612</nlm:aff></affiliation></author><author><name sortKey="Cicek, Mine S" sort="Cicek, Mine S" uniqKey="Cicek M" first="Mine S." last="Cicek">Mine S. Cicek</name><affiliation><nlm:aff id="A31">Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, MN, USA, 55905</nlm:aff></affiliation></author><author><name sortKey="Coetzee, Gerhard A" sort="Coetzee, Gerhard A" uniqKey="Coetzee G" first="Gerhard A." last="Coetzee">Gerhard A. Coetzee</name><affiliation><nlm:aff id="A32">Department of Urology, Microbiology and Preventive Medicine, University of Southern California, Norris Comprehensive Cancer Center, Los Angeles, CA, USA, 90089</nlm:aff></affiliation></author><author><name sortKey="Cook, Linda S" sort="Cook, Linda S" uniqKey="Cook L" first="Linda S." last="Cook">Linda S. Cook</name><affiliation><nlm:aff id="A35">Division Epidemiology and Biostatistics, University of New Mexico, Albuquerque, NM, USA, 87131</nlm:aff></affiliation></author><author><name sortKey="Couch, Fergus J" sort="Couch, Fergus J" uniqKey="Couch F" first="Fergus J." last="Couch">Fergus J. Couch</name><affiliation><nlm:aff id="A34">Department of Laboratory of Medicine and Pathology, Mayo Clinic, Rochester, MN, USA, 55905</nlm:aff></affiliation></author><author><name sortKey="Cramer, Daniel W" sort="Cramer, Daniel W" uniqKey="Cramer D" first="Daniel W." last="Cramer">Daniel W. Cramer</name><affiliation><nlm:aff id="A36">Obstetrics and Gynecology Epidemiology Center, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA, 02115</nlm:aff></affiliation></author><author><name sortKey="Cunningham, Julie M" sort="Cunningham, Julie M" uniqKey="Cunningham J" first="Julie M." last="Cunningham">Julie M. Cunningham</name><affiliation><nlm:aff id="A31">Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, MN, USA, 55905</nlm:aff></affiliation></author><author><name sortKey="Dansonka Mieszkowska, Agnieszka" sort="Dansonka Mieszkowska, Agnieszka" uniqKey="Dansonka Mieszkowska A" first="Agnieszka" last="Dansonka-Mieszkowska">Agnieszka Dansonka-Mieszkowska</name><affiliation><nlm:aff id="A37">Department of Molecular Pathology, The Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland, 02-781</nlm:aff></affiliation></author><author><name sortKey="Despierre, Evelyn" sort="Despierre, Evelyn" uniqKey="Despierre E" first="Evelyn" last="Despierre">Evelyn Despierre</name><affiliation><nlm:aff id="A38">Division of Gynecologic Oncology, Department of Obstetrics and Gynaecology and Leuven Cancer Institute, University Hospitals Leuven, Leuven, Belgium, 3000</nlm:aff></affiliation></author><author><name sortKey="Doherty, Jennifer A" sort="Doherty, Jennifer A" uniqKey="Doherty J" first="Jennifer A" last="Doherty">Jennifer A. Doherty</name><affiliation><nlm:aff id="A39">Section of Biostatistics and Epidemiology, The Geisel School of Medicine at Dartmouth, Lebanon, NH, USA, 03755</nlm:aff></affiliation></author><author><name sortKey="Dork, Thilo" sort="Dork, Thilo" uniqKey="Dork T" first="Thilo" last="Dörk">Thilo Dörk</name><affiliation><nlm:aff id="A21">Gynaecology Research Unit, Hannover Medical School, Hannover, 30625, Germany</nlm:aff></affiliation></author><author><name sortKey="Du Bois, Andreas" sort="Du Bois, Andreas" uniqKey="Du Bois A" first="Andreas" last="Du Bois">Andreas Du Bois</name><affiliation><nlm:aff id="A40">Department of Gynecology and Gynecologic Oncology, Dr. Horst Schmidt Klinik Wiesbaden, 65199, Wiesbaden, Germany</nlm:aff></affiliation><affiliation><nlm:aff id="A41">Department of Gynecology and Gynecologic Oncology, Kliniken Essen-Mitte, 45136, Essen, Germany</nlm:aff></affiliation></author><author><name sortKey="Durst, Matthias" sort="Durst, Matthias" uniqKey="Durst M" first="Matthias" last="Dürst">Matthias Dürst</name><affiliation><nlm:aff id="A42">Department of Gynecology and Obstetrics, Jena University Hospital, 07743, Jena, Germany</nlm:aff></affiliation></author><author><name sortKey="Easton, Douglas F" sort="Easton, Douglas F" uniqKey="Easton D" first="Douglas F" last="Easton">Douglas F. Easton</name><affiliation><nlm:aff id="A11">Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, CB1 8RN, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A43">Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, CB1 8RN, UK</nlm:aff></affiliation></author><author><name sortKey="Eccles, Diana" sort="Eccles, Diana" uniqKey="Eccles D" first="Diana" last="Eccles">Diana Eccles</name><affiliation><nlm:aff id="A44">Faculty of Medicine, University of Southampton, University Hospital Southampton, SO17 1BJ, UK</nlm:aff></affiliation></author><author><name sortKey="Edwards, Robert" sort="Edwards, Robert" uniqKey="Edwards R" first="Robert" last="Edwards">Robert Edwards</name><affiliation><nlm:aff id="A45">Maggee Women's Hospital, Pittsburg, PA, USA, 15213</nlm:aff></affiliation></author><author><name sortKey="Ekici, Arif B" sort="Ekici, Arif B" uniqKey="Ekici A" first="Arif B." last="Ekici">Arif B. Ekici</name><affiliation><nlm:aff id="A46">Institute of Human Genetics, Friedrich-Alexander-University Erlangen-Nuremberg, 91054, Erlangen, Germany</nlm:aff></affiliation></author><author><name sortKey="Fasching, Peter A" sort="Fasching, Peter A" uniqKey="Fasching P" first="Peter A." last="Fasching">Peter A. Fasching</name><affiliation><nlm:aff id="A19">University Hospital Erlangen, Department of Gynecology and Obstetrics, Friedrich-Alexander-University Erlangen-Nuremberg, Comprehensive Cancer Center, Erlangen, 91054, Germany</nlm:aff></affiliation><affiliation><nlm:aff id="A47">Department of Medicine, Division of Hematology and Oncology, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, USA, 90095</nlm:aff></affiliation></author><author><name sortKey="Fenstermacher, David A" sort="Fenstermacher, David A" uniqKey="Fenstermacher D" first="David A." last="Fenstermacher">David A. Fenstermacher</name><affiliation><nlm:aff id="A4">Department of Biomedical Informatics, Moffitt Cancer Center, Tampa, FL, USA, 33612</nlm:aff></affiliation></author><author><name sortKey="Flanagan, James M" sort="Flanagan, James M" uniqKey="Flanagan J" first="James M." last="Flanagan">James M. Flanagan</name><affiliation><nlm:aff id="A24">Department of Surgery and Cancer, Imperial College London, London, SW7 2AZ, UK</nlm:aff></affiliation></author><author><name sortKey="Garcia Closas, Montserrat" sort="Garcia Closas, Montserrat" uniqKey="Garcia Closas M" first="Montserrat" last="Garcia-Closas">Montserrat Garcia-Closas</name><affiliation><nlm:aff id="A48">Sections of Epidemiology and Genetics at the Institute of Cancer Research and Breakthrough Breast Cancer Research Centre, London, UK, SW7 3RP</nlm:aff></affiliation></author><author><name sortKey="Gentry Maharaj, Aleksandra" sort="Gentry Maharaj, Aleksandra" uniqKey="Gentry Maharaj A" first="Aleksandra" last="Gentry-Maharaj">Aleksandra Gentry-Maharaj</name><affiliation><nlm:aff id="A49">Gynaecological Cancer Research Centre, UCL EGA Institute for Women's Health, London, NW1 2BU, United Kingdom</nlm:aff></affiliation></author><author><name sortKey="Giles, Graham G" sort="Giles, Graham G" uniqKey="Giles G" first="Graham G." last="Giles">Graham G. Giles</name><affiliation><nlm:aff id="A15">Cancer Epidemiology Centre, The Cancer Council Victoria, Melbourne, Carlton VIC 3053, Australia</nlm:aff></affiliation><affiliation><nlm:aff id="A16">Centre for Molecular, Environmental, Genetic and Analytical Epidemiology, University of Melbourne, Melbourne, VIC 3010, Australia</nlm:aff></affiliation><affiliation><nlm:aff id="A50">Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, VIC 3806, Australia</nlm:aff></affiliation></author><author><name sortKey="Glasspool, Rosalind M" sort="Glasspool, Rosalind M" uniqKey="Glasspool R" first="Rosalind M." last="Glasspool">Rosalind M. Glasspool</name><affiliation><nlm:aff id="A51">The Beatson West of Scotland Cancer Centre, Glasgow, G12 0YN, UK</nlm:aff></affiliation></author><author><name sortKey="Gonzalez Bosquet, Jesus" sort="Gonzalez Bosquet, Jesus" uniqKey="Gonzalez Bosquet J" first="Jesus" last="Gonzalez-Bosquet">Jesus Gonzalez-Bosquet</name><affiliation><nlm:aff id="A52">Department of Women's Oncology, Moffitt Cancer Center, Tampa, FL, USA, 33612</nlm:aff></affiliation></author><author><name sortKey="Goodman, Marc T" sort="Goodman, Marc T" uniqKey="Goodman M" first="Marc T." last="Goodman">Marc T. Goodman</name><affiliation><nlm:aff id="A53">Samuel Oschin Comprehensive Cancer Center Institute, Cedars Sinai Medical Center, Los Angeles, CA, USA, 90048</nlm:aff></affiliation></author><author><name sortKey="Gore, Martin" sort="Gore, Martin" uniqKey="Gore M" first="Martin" last="Gore">Martin Gore</name><affiliation><nlm:aff id="A54">Gynecological Oncology Unit, The Royal Marsden Hospital, London, SW3 6JJ, United Kingdom</nlm:aff></affiliation></author><author><name sortKey="G Rski, Bohdan" sort="G Rski, Bohdan" uniqKey="G Rski B" first="Bohdan" last="G Rski">Bohdan G Rski</name><affiliation><nlm:aff id="A55">International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland, 70-115</nlm:aff></affiliation></author><author><name sortKey="Gronwald, Jacek" sort="Gronwald, Jacek" uniqKey="Gronwald J" first="Jacek" last="Gronwald">Jacek Gronwald</name><affiliation><nlm:aff id="A55">International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland, 70-115</nlm:aff></affiliation></author><author><name sortKey="Hall, Per" sort="Hall, Per" uniqKey="Hall P" first="Per" last="Hall">Per Hall</name><affiliation><nlm:aff id="A56">Department of Epidemiology and Biostatistics, Karolinska Istitutet, Stockholm, Sweden, 171-77</nlm:aff></affiliation></author><author><name sortKey="Halle, Mari K" sort="Halle, Mari K" uniqKey="Halle M" first="Mari K." last="Halle">Mari K. Halle</name><affiliation><nlm:aff id="A57">Department of Gynecology and Obstetrics, Haukeland University Hospital, Bergen, HB 5006, Norway</nlm:aff></affiliation><affiliation><nlm:aff id="A58">Department of Clinical Medicine, University of Bergen, 5006, Bergen, Norway</nlm:aff></affiliation></author><author><name sortKey="Harter, Philipp" sort="Harter, Philipp" uniqKey="Harter P" first="Philipp" last="Harter">Philipp Harter</name><affiliation><nlm:aff id="A40">Department of Gynecology and Gynecologic Oncology, Dr. Horst Schmidt Klinik Wiesbaden, 65199, Wiesbaden, Germany</nlm:aff></affiliation><affiliation><nlm:aff id="A41">Department of Gynecology and Gynecologic Oncology, Kliniken Essen-Mitte, 45136, Essen, Germany</nlm:aff></affiliation></author><author><name sortKey="Heitz, Florian" sort="Heitz, Florian" uniqKey="Heitz F" first="Florian" last="Heitz">Florian Heitz</name><affiliation><nlm:aff id="A40">Department of Gynecology and Gynecologic Oncology, Dr. Horst Schmidt Klinik Wiesbaden, 65199, Wiesbaden, Germany</nlm:aff></affiliation><affiliation><nlm:aff id="A41">Department of Gynecology and Gynecologic Oncology, Kliniken Essen-Mitte, 45136, Essen, Germany</nlm:aff></affiliation></author><author><name sortKey="Hillemanns, Peter" sort="Hillemanns, Peter" uniqKey="Hillemanns P" first="Peter" last="Hillemanns">Peter Hillemanns</name><affiliation><nlm:aff id="A59">Clinics of Obstetrics and Gynaecology, Hannover Medical School, 30625, Hannover, Germany</nlm:aff></affiliation></author><author><name sortKey="Hoatlin, Maureen" sort="Hoatlin, Maureen" uniqKey="Hoatlin M" first="Maureen" last="Hoatlin">Maureen Hoatlin</name><affiliation><nlm:aff id="A60">Department of Biochemistry and Molecular Biology, Oregon Health and Science University, Portland, OR, USA, 97239</nlm:aff></affiliation></author><author><name sortKey="H Gdall, Claus K" sort="H Gdall, Claus K" uniqKey="H Gdall C" first="Claus K." last="H Gdall">Claus K. H Gdall</name><affiliation><nlm:aff id="A61">The Juliane Marie Centre, Department of Obstetrics and Gynecology, Rigshospitalet, Copenhagen, 2100, Denmark</nlm:aff></affiliation></author><author><name sortKey="H Gdall, Estrid" sort="H Gdall, Estrid" uniqKey="H Gdall E" first="Estrid" last="H Gdall">Estrid H Gdall</name><affiliation><nlm:aff id="A62">Department of Pathology, Molecular Unit, Herlev Hospital, University of Copenhagen, Denmark, 2730</nlm:aff></affiliation><affiliation><nlm:aff id="A63">Virus, Lifestyle and Genes, Danish Cancer Society Research Center, DK-2100, Copenhagen, Denmark</nlm:aff></affiliation></author><author><name sortKey="Hosono, Satoyo" sort="Hosono, Satoyo" uniqKey="Hosono S" first="Satoyo" last="Hosono">Satoyo Hosono</name><affiliation><nlm:aff id="A64">Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya, Aichi, 464-8681, Japan</nlm:aff></affiliation></author><author><name sortKey="Jakubowska, Anna" sort="Jakubowska, Anna" uniqKey="Jakubowska A" first="Anna" last="Jakubowska">Anna Jakubowska</name><affiliation><nlm:aff id="A55">International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland, 70-115</nlm:aff></affiliation></author><author><name sortKey="Jensen, Allan" sort="Jensen, Allan" uniqKey="Jensen A" first="Allan" last="Jensen">Allan Jensen</name><affiliation><nlm:aff id="A63">Virus, Lifestyle and Genes, Danish Cancer Society Research Center, DK-2100, Copenhagen, Denmark</nlm:aff></affiliation></author><author><name sortKey="Jim, Heather" sort="Jim, Heather" uniqKey="Jim H" first="Heather" last="Jim">Heather Jim</name><affiliation><nlm:aff id="A65">Department of Health Outcomes and Behavior, Moffitt Cancer Center, Tampa, FL, USA, 33612</nlm:aff></affiliation></author><author><name sortKey="Kalli, Kimberly R" sort="Kalli, Kimberly R" uniqKey="Kalli K" first="Kimberly R." last="Kalli">Kimberly R. Kalli</name><affiliation><nlm:aff id="A66">Department of Medical Oncology, Mayo Clinic, Rochester, MN, USA, 55905</nlm:aff></affiliation></author><author><name sortKey="Karlan, Beth Y" sort="Karlan, Beth Y" uniqKey="Karlan B" first="Beth Y." last="Karlan">Beth Y. Karlan</name><affiliation><nlm:aff id="A67">Women's Cancer Program at the Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA, 90048</nlm:aff></affiliation></author><author><name sortKey="Kaye, Stanley B" sort="Kaye, Stanley B" uniqKey="Kaye S" first="Stanley B." last="Kaye">Stanley B. Kaye</name><affiliation><nlm:aff id="A68">Section of Medicine, Institute of Cancer Research, Sutton, SM2 5NG, UK</nlm:aff></affiliation></author><author><name sortKey="Kelemen, Linda E" sort="Kelemen, Linda E" uniqKey="Kelemen L" first="Linda E." last="Kelemen">Linda E. Kelemen</name><affiliation><nlm:aff id="A69">Department of Popluation Health Research, Alberta Health Services-Cancer Care, Calgary, Alberta, Canada and Departments of Medical Genetics and Oncology, University of Calgary, Calgary, AB, Canada, T2N 2T9</nlm:aff></affiliation></author><author><name sortKey="Kiemeney, Lambertus A" sort="Kiemeney, Lambertus A" uniqKey="Kiemeney L" first="Lambertus A." last="Kiemeney">Lambertus A. Kiemeney</name><affiliation><nlm:aff id="A7">Department of Epidemiology, Biostatistics and HTA, Radboud University Medical Centre, Nijmegen, HB 6500, Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A8">Comprehensive Cancer Center, the Netherlands, Utrecht, Amsterdam, 1066CX, The Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A70">Department of Urology, Radboud University Medical Centre, Nijmegen, HB 6500, Netherlands</nlm:aff></affiliation></author><author><name sortKey="Kikkawa, Fumitaka" sort="Kikkawa, Fumitaka" uniqKey="Kikkawa F" first="Fumitaka" last="Kikkawa">Fumitaka Kikkawa</name><affiliation><nlm:aff id="A71">Department of Obsterics and Gynecology, Nagoya University Graduate School of Medicine, Nagoya, Aichi, 466-8550, Japan</nlm:aff></affiliation></author><author><name sortKey="Konecny, Gottfried E" sort="Konecny, Gottfried E" uniqKey="Konecny G" first="Gottfried E." last="Konecny">Gottfried E. Konecny</name><affiliation><nlm:aff id="A47">Department of Medicine, Division of Hematology and Oncology, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, USA, 90095</nlm:aff></affiliation></author><author><name sortKey="Krakstad, Camilla" sort="Krakstad, Camilla" uniqKey="Krakstad C" first="Camilla" last="Krakstad">Camilla Krakstad</name><affiliation><nlm:aff id="A57">Department of Gynecology and Obstetrics, Haukeland University Hospital, Bergen, HB 5006, Norway</nlm:aff></affiliation><affiliation><nlm:aff id="A58">Department of Clinical Medicine, University of Bergen, 5006, Bergen, Norway</nlm:aff></affiliation></author><author><name sortKey="Kjaer, Susanne Kruger" sort="Kjaer, Susanne Kruger" uniqKey="Kjaer S" first="Susanne Krüger" last="Kjaer">Susanne Krüger Kjaer</name><affiliation><nlm:aff id="A61">The Juliane Marie Centre, Department of Obstetrics and Gynecology, Rigshospitalet, Copenhagen, 2100, Denmark</nlm:aff></affiliation><affiliation><nlm:aff id="A63">Virus, Lifestyle and Genes, Danish Cancer Society Research Center, DK-2100, Copenhagen, Denmark</nlm:aff></affiliation></author><author><name sortKey="Kupryjanczyk, Jolanta" sort="Kupryjanczyk, Jolanta" uniqKey="Kupryjanczyk J" first="Jolanta" last="Kupryjanczyk">Jolanta Kupryjanczyk</name><affiliation><nlm:aff id="A37">Department of Molecular Pathology, The Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland, 02-781</nlm:aff></affiliation></author><author><name sortKey="Lambrechts, Diether" sort="Lambrechts, Diether" uniqKey="Lambrechts D" first="Diether" last="Lambrechts">Diether Lambrechts</name><affiliation><nlm:aff id="A72">Vesalius Research Center, VIB, 3000, Leuven, Belgium</nlm:aff></affiliation><affiliation><nlm:aff id="A73">Laboratory for Translational Genetics, Department of Oncology, University of Leuven, 3000, Leuven, Belgium</nlm:aff></affiliation></author><author><name sortKey="Lambrechts, Sandrina" sort="Lambrechts, Sandrina" uniqKey="Lambrechts S" first="Sandrina" last="Lambrechts">Sandrina Lambrechts</name><affiliation><nlm:aff id="A38">Division of Gynecologic Oncology, Department of Obstetrics and Gynaecology and Leuven Cancer Institute, University Hospitals Leuven, Leuven, Belgium, 3000</nlm:aff></affiliation></author><author><name sortKey="Lancaster, Johnathan M" sort="Lancaster, Johnathan M" uniqKey="Lancaster J" first="Johnathan M." last="Lancaster">Johnathan M. Lancaster</name><affiliation><nlm:aff id="A52">Department of Women's Oncology, Moffitt Cancer Center, Tampa, FL, USA, 33612</nlm:aff></affiliation></author><author><name sortKey="Le, Nhu D" sort="Le, Nhu D" uniqKey="Le N" first="Nhu D." last="Le">Nhu D. Le</name><affiliation><nlm:aff id="A74">Cancer Control Research, BC Cancer Agency, Vancouver, BC, Canada, G12 0YN</nlm:aff></affiliation></author><author><name sortKey="Leminen, Arto" sort="Leminen, Arto" uniqKey="Leminen A" first="Arto" last="Leminen">Arto Leminen</name><affiliation><nlm:aff id="A26">Department of Obstetrics and Gynecology, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland, 00530</nlm:aff></affiliation></author><author><name sortKey="Levine, Douglas A" sort="Levine, Douglas A" uniqKey="Levine D" first="Douglas A." last="Levine">Douglas A. Levine</name><affiliation><nlm:aff id="A75">Gynecology Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY, USA, 10021</nlm:aff></affiliation></author><author><name sortKey="Liang, Dong" sort="Liang, Dong" uniqKey="Liang D" first="Dong" last="Liang">Dong Liang</name><affiliation><nlm:aff id="A76">College of Pharmacy and Health Sciences, Texas Southern University, Houston, Texas, USA, 77044</nlm:aff></affiliation></author><author><name sortKey="Lim, Boon Kiong" sort="Lim, Boon Kiong" uniqKey="Lim B" first="Boon Kiong" last="Lim">Boon Kiong Lim</name><affiliation><nlm:aff id="A77">Department of Obstetrics and Gynaecology, University Malaya Medical Centre, University Malaya, 59100 Kuala Lumpur, Federal Territory of Kuala Lumpur, Malaysia</nlm:aff></affiliation></author><author><name sortKey="Lin, Jie" sort="Lin, Jie" uniqKey="Lin J" first="Jie" last="Lin">Jie Lin</name><affiliation><nlm:aff id="A78">Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA, 77030</nlm:aff></affiliation></author><author><name sortKey="Lissowska, Jolanta" sort="Lissowska, Jolanta" uniqKey="Lissowska J" first="Jolanta" last="Lissowska">Jolanta Lissowska</name><affiliation><nlm:aff id="A79">Department of Cancer Epidemiology and Prevention, The Maria Sklodowska-Curie Memorial Cancer Center, 02-781, Warsaw, Poland</nlm:aff></affiliation></author><author><name sortKey="Lu, Karen H" sort="Lu, Karen H" uniqKey="Lu K" first="Karen H." last="Lu">Karen H. Lu</name><affiliation><nlm:aff id="A80">Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA, 77030</nlm:aff></affiliation></author><author><name sortKey="Lubi Ski, Jan" sort="Lubi Ski, Jan" uniqKey="Lubi Ski J" first="Jan" last="Lubi Ski">Jan Lubi Ski</name><affiliation><nlm:aff id="A55">International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland, 70-115</nlm:aff></affiliation></author><author><name sortKey="Lurie, Galina" sort="Lurie, Galina" uniqKey="Lurie G" first="Galina" last="Lurie">Galina Lurie</name><affiliation><nlm:aff id="A81">Cancer Epidemiology Program, University of Hawaii Cancer Center, Hawaii, USA, 96813</nlm:aff></affiliation></author><author><name sortKey="Massuger, Leon F A G" sort="Massuger, Leon F A G" uniqKey="Massuger L" first="Leon F. A. G." last="Massuger">Leon F. A. G. Massuger</name><affiliation><nlm:aff id="A82">Department of Gynaecology, Radboud University Medical Centre, Nijmegen, HB 6500, Netherlands</nlm:aff></affiliation></author><author><name sortKey="Matsuo, Keitaro" sort="Matsuo, Keitaro" uniqKey="Matsuo K" first="Keitaro" last="Matsuo">Keitaro Matsuo</name><affiliation><nlm:aff id="A64">Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya, Aichi, 464-8681, Japan</nlm:aff></affiliation></author><author><name sortKey="Mcguire, Valerie" sort="Mcguire, Valerie" uniqKey="Mcguire V" first="Valerie" last="Mcguire">Valerie Mcguire</name><affiliation><nlm:aff id="A83">Department of Health Research and Policy - Epidemiology, Stanford University School of Medicine, Stanford CA, USA, 94305</nlm:aff></affiliation></author><author><name sortKey="Mclaughlin, John R" sort="Mclaughlin, John R" uniqKey="Mclaughlin J" first="John R" last="Mclaughlin">John R. Mclaughlin</name><affiliation><nlm:aff id="A84">Dalla Lana School of Public Health, Faculty of Medicine, University of Toronto, ON, M5T 3M7, Canada</nlm:aff></affiliation><affiliation><nlm:aff id="A85">Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada, M5G 1X5</nlm:aff></affiliation></author><author><name sortKey="Menon, Usha" sort="Menon, Usha" uniqKey="Menon U" first="Usha" last="Menon">Usha Menon</name><affiliation><nlm:aff id="A49">Gynaecological Cancer Research Centre, UCL EGA Institute for Women's Health, London, NW1 2BU, United Kingdom</nlm:aff></affiliation></author><author><name sortKey="Modugno, Francesmary" sort="Modugno, Francesmary" uniqKey="Modugno F" first="Francesmary" last="Modugno">Francesmary Modugno</name><affiliation><nlm:aff id="A78">Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA, 77030</nlm:aff></affiliation><affiliation><nlm:aff id="A80">Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA, 77030</nlm:aff></affiliation><affiliation><nlm:aff id="A86">Women's Cancer Research Program, Magee-Womens Research Institute and University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA, 15213</nlm:aff></affiliation></author><author><name sortKey="Moysich, Kirsten B" sort="Moysich, Kirsten B" uniqKey="Moysich K" first="Kirsten B." last="Moysich">Kirsten B. Moysich</name><affiliation><nlm:aff id="A87">Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, NY, USA, 14263</nlm:aff></affiliation></author><author><name sortKey="Nakanishi, Toru" sort="Nakanishi, Toru" uniqKey="Nakanishi T" first="Toru" last="Nakanishi">Toru Nakanishi</name><affiliation><nlm:aff id="A88">Department of Gynecologic Oncology, Aichi Cancer Center Central Hospital, Nagoya, Aichi, Nagoya, 464-8681, Japan</nlm:aff></affiliation></author><author><name sortKey="Narod, Steven A" sort="Narod, Steven A" uniqKey="Narod S" first="Steven A." last="Narod">Steven A. Narod</name><affiliation><nlm:aff id="A89">Women's College Research Institute, University of Toronto, Toronto, Ontario, Canada, M5G 1N8</nlm:aff></affiliation></author><author><name sortKey="Nedergaard, Lotte" sort="Nedergaard, Lotte" uniqKey="Nedergaard L" first="Lotte" last="Nedergaard">Lotte Nedergaard</name><affiliation><nlm:aff id="A90">Department of Pathology, Rigshospitalet, University of Copenhagen, 2100, Denmark</nlm:aff></affiliation></author><author><name sortKey="Ness, Roberta B" sort="Ness, Roberta B" uniqKey="Ness R" first="Roberta B." last="Ness">Roberta B. Ness</name><affiliation><nlm:aff id="A91">The University of Texas School of Public Health, Houston, TX, USA, 77030</nlm:aff></affiliation></author><author><name sortKey="Nevanlinna, Heli" sort="Nevanlinna, Heli" uniqKey="Nevanlinna H" first="Heli" last="Nevanlinna">Heli Nevanlinna</name><affiliation><nlm:aff id="A26">Department of Obstetrics and Gynecology, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland, 00530</nlm:aff></affiliation></author><author><name sortKey="Nickels, Stefan" sort="Nickels, Stefan" uniqKey="Nickels S" first="Stefan" last="Nickels">Stefan Nickels</name><affiliation><nlm:aff id="A29">German Cancer Research Center, Division of Cancer Epidemiology, 69120, Heidelberg, Germany</nlm:aff></affiliation></author><author><name sortKey="Noushmehr, Houtan" sort="Noushmehr, Houtan" uniqKey="Noushmehr H" first="Houtan" last="Noushmehr">Houtan Noushmehr</name><affiliation><nlm:aff id="A32">Department of Urology, Microbiology and Preventive Medicine, University of Southern California, Norris Comprehensive Cancer Center, Los Angeles, CA, USA, 90089</nlm:aff></affiliation><affiliation><nlm:aff id="A92">USC Epigenome Center, Keck School of Medicine, University of Southern California, Norris Comprehensive Cancer Center, Los Angeles, CA, 90089</nlm:aff></affiliation></author><author><name sortKey="Odunsi, Kunle" sort="Odunsi, Kunle" uniqKey="Odunsi K" first="Kunle" last="Odunsi">Kunle Odunsi</name><affiliation><nlm:aff id="A93">Department of Gynecologic Oncology, Roswell Park Cancer Institute, Buffalo, NY, USA, 14263</nlm:aff></affiliation></author><author><name sortKey="Olson, Sara H" sort="Olson, Sara H" uniqKey="Olson S" first="Sara H." last="Olson">Sara H. Olson</name><affiliation><nlm:aff id="A94">Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY, USA, 10065</nlm:aff></affiliation></author><author><name sortKey="Orlow, Irene" sort="Orlow, Irene" uniqKey="Orlow I" first="Irene" last="Orlow">Irene Orlow</name><affiliation><nlm:aff id="A94">Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY, USA, 10065</nlm:aff></affiliation></author><author><name sortKey="Paul, James" sort="Paul, James" uniqKey="Paul J" first="James" last="Paul">James Paul</name><affiliation><nlm:aff id="A51">The Beatson West of Scotland Cancer Centre, Glasgow, G12 0YN, UK</nlm:aff></affiliation></author><author><name sortKey="Pearce, Celeste L" sort="Pearce, Celeste L" uniqKey="Pearce C" first="Celeste L" last="Pearce">Celeste L. Pearce</name><affiliation><nlm:aff id="A2">Department of Preventive Medicine, Keck School of Medicine, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA, USA, 90033</nlm:aff></affiliation></author><author><name sortKey="Pejovic, Tanja" sort="Pejovic, Tanja" uniqKey="Pejovic T" first="Tanja" last="Pejovic">Tanja Pejovic</name><affiliation><nlm:aff id="A95">Department of Obstetrics and Gynecology, Oregon Health and Science University, Portland, OR, USA, 97239</nlm:aff></affiliation><affiliation><nlm:aff id="A96">Knight Cancer Institute, Oregon Health and Science University, Portland, OR, USA, 97239</nlm:aff></affiliation></author><author><name sortKey="Pelttari, Liisa M" sort="Pelttari, Liisa M" uniqKey="Pelttari L" first="Liisa M." last="Pelttari">Liisa M. Pelttari</name><affiliation><nlm:aff id="A26">Department of Obstetrics and Gynecology, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland, 00530</nlm:aff></affiliation></author><author><name sortKey="Pike, Malcolm C" sort="Pike, Malcolm C" uniqKey="Pike M" first="Malcolm C." last="Pike">Malcolm C. Pike</name><affiliation><nlm:aff id="A2">Department of Preventive Medicine, Keck School of Medicine, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA, USA, 90033</nlm:aff></affiliation><affiliation><nlm:aff id="A94">Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY, USA, 10065</nlm:aff></affiliation></author><author><name sortKey="Poole, Elizabeth M" sort="Poole, Elizabeth M" uniqKey="Poole E" first="Elizabeth M." last="Poole">Elizabeth M. Poole</name><affiliation><nlm:aff id="A97">Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA, 02115</nlm:aff></affiliation><affiliation><nlm:aff id="A98">Channing Laboratory, Harvard Medical School and Brigham and Women's Hospital, Boston, MA, USA, 02115</nlm:aff></affiliation></author><author><name sortKey="Raska, Paola" sort="Raska, Paola" uniqKey="Raska P" first="Paola" last="Raska">Paola Raska</name><affiliation><nlm:aff id="A18">Case Comprehensive Cancer Center, Case Western Reserve University School of Medicine, Cleveland, OH, USA, 44195</nlm:aff></affiliation></author><author><name sortKey="Renner, Stefan P" sort="Renner, Stefan P" uniqKey="Renner S" first="Stefan P." last="Renner">Stefan P. Renner</name><affiliation><nlm:aff id="A19">University Hospital Erlangen, Department of Gynecology and Obstetrics, Friedrich-Alexander-University Erlangen-Nuremberg, Comprehensive Cancer Center, Erlangen, 91054, Germany</nlm:aff></affiliation></author><author><name sortKey="Risch, Harvey A" sort="Risch, Harvey A" uniqKey="Risch H" first="Harvey A." last="Risch">Harvey A. Risch</name><affiliation><nlm:aff id="A99">Department of Epidemiology and Public Health, Yale University School of Public Health and School of Medicine, New Haven, CT, USA, 06520</nlm:aff></affiliation></author><author><name sortKey="Rodriguez Rodriguez, Lorna" sort="Rodriguez Rodriguez, Lorna" uniqKey="Rodriguez Rodriguez L" first="Lorna" last="Rodriguez-Rodriguez">Lorna Rodriguez-Rodriguez</name><affiliation><nlm:aff id="A17">The Cancer Institute of New Jersey, Robert Wood Johnson Medical School, New Brunswick, NJ, USA, 08901</nlm:aff></affiliation></author><author><name sortKey="Rossing, Mary Anne" sort="Rossing, Mary Anne" uniqKey="Rossing M" first="Mary Anne" last="Rossing">Mary Anne Rossing</name><affiliation><nlm:aff id="A100">Program in Epidemiology, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA, 98109</nlm:aff></affiliation><affiliation><nlm:aff id="A101">Department of Epidemiology, University of Washington, Seattle, WA, USA, 98109</nlm:aff></affiliation></author><author><name sortKey="Rudolph, Anja" sort="Rudolph, Anja" uniqKey="Rudolph A" first="Anja" last="Rudolph">Anja Rudolph</name><affiliation><nlm:aff id="A29">German Cancer Research Center, Division of Cancer Epidemiology, 69120, Heidelberg, Germany</nlm:aff></affiliation></author><author><name sortKey="Runnebaum, Ingo B" sort="Runnebaum, Ingo B" uniqKey="Runnebaum I" first="Ingo B." last="Runnebaum">Ingo B. Runnebaum</name><affiliation><nlm:aff id="A42">Department of Gynecology and Obstetrics, Jena University Hospital, 07743, Jena, Germany</nlm:aff></affiliation></author><author><name sortKey="Rzepecka, Iwona K" sort="Rzepecka, Iwona K" uniqKey="Rzepecka I" first="Iwona K." last="Rzepecka">Iwona K. Rzepecka</name><affiliation><nlm:aff id="A37">Department of Molecular Pathology, The Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland, 02-781</nlm:aff></affiliation></author><author><name sortKey="Salvesen, Helga B" sort="Salvesen, Helga B" uniqKey="Salvesen H" first="Helga B." last="Salvesen">Helga B. Salvesen</name><affiliation><nlm:aff id="A57">Department of Gynecology and Obstetrics, Haukeland University Hospital, Bergen, HB 5006, Norway</nlm:aff></affiliation><affiliation><nlm:aff id="A58">Department of Clinical Medicine, University of Bergen, 5006, Bergen, Norway</nlm:aff></affiliation></author><author><name sortKey="Schwaab, Ira" sort="Schwaab, Ira" uniqKey="Schwaab I" first="Ira" last="Schwaab">Ira Schwaab</name><affiliation><nlm:aff id="A102">Institut für Humangenetik Wiesbaden, 65187, Wiesbaden, Germany</nlm:aff></affiliation></author><author><name sortKey="Severi, Gianluca" sort="Severi, Gianluca" uniqKey="Severi G" first="Gianluca" last="Severi">Gianluca Severi</name><affiliation><nlm:aff id="A15">Cancer Epidemiology Centre, The Cancer Council Victoria, Melbourne, Carlton VIC 3053, Australia</nlm:aff></affiliation><affiliation><nlm:aff id="A16">Centre for Molecular, Environmental, Genetic and Analytical Epidemiology, University of Melbourne, Melbourne, VIC 3010, Australia</nlm:aff></affiliation></author><author><name sortKey="Shridhar, Vijayalakshmi" sort="Shridhar, Vijayalakshmi" uniqKey="Shridhar V" first="Vijayalakshmi" last="Shridhar">Vijayalakshmi Shridhar</name><affiliation><nlm:aff id="A103">Department of Laboratory Medicine and Pathology, Division of Anatomic Pathology, Mayo Clinic, Rochester, MN, USA, 55905</nlm:aff></affiliation></author><author><name sortKey="Shu, Xiao Ou" sort="Shu, Xiao Ou" uniqKey="Shu X" first="Xiao-Ou" last="Shu">Xiao-Ou Shu</name><affiliation><nlm:aff id="A27">Vanderbilt Epidemiology Center and Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN, USA, 37232</nlm:aff></affiliation></author><author><name sortKey="Shvetsov, Yurii B" sort="Shvetsov, Yurii B" uniqKey="Shvetsov Y" first="Yurii B." last="Shvetsov">Yurii B. Shvetsov</name><affiliation><nlm:aff id="A81">Cancer Epidemiology Program, University of Hawaii Cancer Center, Hawaii, USA, 96813</nlm:aff></affiliation></author><author><name sortKey="Sieh, Weiva" sort="Sieh, Weiva" uniqKey="Sieh W" first="Weiva" last="Sieh">Weiva Sieh</name><affiliation><nlm:aff id="A83">Department of Health Research and Policy - Epidemiology, Stanford University School of Medicine, Stanford CA, USA, 94305</nlm:aff></affiliation></author><author><name sortKey="Song, Honglin" sort="Song, Honglin" uniqKey="Song H" first="Honglin" last="Song">Honglin Song</name><affiliation><nlm:aff id="A3">Department of Oncology, University of Cambridge, Cambridge, CB1 8RN, UK</nlm:aff></affiliation></author><author><name sortKey="Southey, Melissa C" sort="Southey, Melissa C" uniqKey="Southey M" first="Melissa C." last="Southey">Melissa C. Southey</name><affiliation><nlm:aff id="A104">Genetic Epidemiology Laboratory, Department of Pathology, The University of Melbourne, Melbourne, VIC 3053, Australia</nlm:aff></affiliation></author><author><name sortKey="Spiewankiewicz, Beata" sort="Spiewankiewicz, Beata" uniqKey="Spiewankiewicz B" first="Beata" last="Spiewankiewicz">Beata Spiewankiewicz</name><affiliation><nlm:aff id="A105">Department of Gynecologic Oncology, The Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland, 02-781</nlm:aff></affiliation></author><author><name sortKey="Stram, Daniel" sort="Stram, Daniel" uniqKey="Stram D" first="Daniel" last="Stram">Daniel Stram</name><affiliation><nlm:aff id="A2">Department of Preventive Medicine, Keck School of Medicine, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA, USA, 90033</nlm:aff></affiliation></author><author><name sortKey="Sutphen, Rebecca" sort="Sutphen, Rebecca" uniqKey="Sutphen R" first="Rebecca" last="Sutphen">Rebecca Sutphen</name><affiliation><nlm:aff id="A106">Pediatrics Epidemiology Center, College of Medicine, University of South Florida, Tampa, FL, USA, 33612</nlm:aff></affiliation></author><author><name sortKey="Teo, Soo Hwang" sort="Teo, Soo Hwang" uniqKey="Teo S" first="Soo-Hwang" last="Teo">Soo-Hwang Teo</name><affiliation><nlm:aff id="A77">Department of Obstetrics and Gynaecology, University Malaya Medical Centre, University Malaya, 59100 Kuala Lumpur, Federal Territory of Kuala Lumpur, Malaysia</nlm:aff></affiliation></author><author><name sortKey="Terry, Kathryn L" sort="Terry, Kathryn L" uniqKey="Terry K" first="Kathryn L." last="Terry">Kathryn L. Terry</name><affiliation><nlm:aff id="A36">Obstetrics and Gynecology Epidemiology Center, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA, 02115</nlm:aff></affiliation></author><author><name sortKey="Tessier, Daniel C" sort="Tessier, Daniel C" uniqKey="Tessier D" first="Daniel C." last="Tessier">Daniel C. Tessier</name><affiliation><nlm:aff id="A14">McGill University and Génome Québec Innovation Centre, Montréal (Québec) Canada, H3A 0G1</nlm:aff></affiliation></author><author><name sortKey="Thompson, Pamela J" sort="Thompson, Pamela J" uniqKey="Thompson P" first="Pamela J." last="Thompson">Pamela J. Thompson</name><affiliation><nlm:aff id="A53">Samuel Oschin Comprehensive Cancer Center Institute, Cedars Sinai Medical Center, Los Angeles, CA, USA, 90048</nlm:aff></affiliation></author><author><name sortKey="Tworoger, Shelley S" sort="Tworoger, Shelley S" uniqKey="Tworoger S" first="Shelley S." last="Tworoger">Shelley S. Tworoger</name><affiliation><nlm:aff id="A97">Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA, 02115</nlm:aff></affiliation><affiliation><nlm:aff id="A98">Channing Laboratory, Harvard Medical School and Brigham and Women's Hospital, Boston, MA, USA, 02115</nlm:aff></affiliation></author><author><name sortKey="Van Altena, Anne M" sort="Van Altena, Anne M" uniqKey="Van Altena A" first="Anne M." last="Van Altena">Anne M. Van Altena</name><affiliation><nlm:aff id="A82">Department of Gynaecology, Radboud University Medical Centre, Nijmegen, HB 6500, Netherlands</nlm:aff></affiliation></author><author><name sortKey="Vergote, Ignace" sort="Vergote, Ignace" uniqKey="Vergote I" first="Ignace" last="Vergote">Ignace Vergote</name><affiliation><nlm:aff id="A38">Division of Gynecologic Oncology, Department of Obstetrics and Gynaecology and Leuven Cancer Institute, University Hospitals Leuven, Leuven, Belgium, 3000</nlm:aff></affiliation></author><author><name sortKey="Vierkant, Robert A" sort="Vierkant, Robert A" uniqKey="Vierkant R" first="Robert A." last="Vierkant">Robert A. Vierkant</name><affiliation><nlm:aff id="A31">Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, MN, USA, 55905</nlm:aff></affiliation></author><author><name sortKey="Vincent, Daniel" sort="Vincent, Daniel" uniqKey="Vincent D" first="Daniel" last="Vincent">Daniel Vincent</name><affiliation><nlm:aff id="A14">McGill University and Génome Québec Innovation Centre, Montréal (Québec) Canada, H3A 0G1</nlm:aff></affiliation></author><author><name sortKey="Vitonis, Allison F" sort="Vitonis, Allison F" uniqKey="Vitonis A" first="Allison F." last="Vitonis">Allison F. Vitonis</name><affiliation><nlm:aff id="A36">Obstetrics and Gynecology Epidemiology Center, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA, 02115</nlm:aff></affiliation></author><author><name sortKey="Wang Gohrke, Shan" sort="Wang Gohrke, Shan" uniqKey="Wang Gohrke S" first="Shan" last="Wang-Gohrke">Shan Wang-Gohrke</name><affiliation><nlm:aff id="A107">Department of Obstetrics and Gynecology, University of Ulm, Ulm, 89081, Germany</nlm:aff></affiliation></author><author><name sortKey="Weber, Rachel Palmieri" sort="Weber, Rachel Palmieri" uniqKey="Weber R" first="Rachel Palmieri" last="Weber">Rachel Palmieri Weber</name><affiliation><nlm:aff id="A108">Department of Community and Family Medicine, Duke University Medical Center, Durham, NC, USA, 27708</nlm:aff></affiliation></author><author><name sortKey="Wentzensen, Nicolas" sort="Wentzensen, Nicolas" uniqKey="Wentzensen N" first="Nicolas" last="Wentzensen">Nicolas Wentzensen</name><affiliation><nlm:aff id="A22">Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda MD, USA, 20892</nlm:aff></affiliation></author><author><name sortKey="Whittemore, Alice S" sort="Whittemore, Alice S" uniqKey="Whittemore A" first="Alice S." last="Whittemore">Alice S. Whittemore</name><affiliation><nlm:aff id="A83">Department of Health Research and Policy - Epidemiology, Stanford University School of Medicine, Stanford CA, USA, 94305</nlm:aff></affiliation></author><author><name sortKey="Wik, Elisabeth" sort="Wik, Elisabeth" uniqKey="Wik E" first="Elisabeth" last="Wik">Elisabeth Wik</name><affiliation><nlm:aff id="A57">Department of Gynecology and Obstetrics, Haukeland University Hospital, Bergen, HB 5006, Norway</nlm:aff></affiliation><affiliation><nlm:aff id="A58">Department of Clinical Medicine, University of Bergen, 5006, Bergen, Norway</nlm:aff></affiliation></author><author><name sortKey="Wilkens, Lynne R" sort="Wilkens, Lynne R" uniqKey="Wilkens L" first="Lynne R." last="Wilkens">Lynne R. Wilkens</name><affiliation><nlm:aff id="A81">Cancer Epidemiology Program, University of Hawaii Cancer Center, Hawaii, USA, 96813</nlm:aff></affiliation></author><author><name sortKey="Winterhoff, Boris" sort="Winterhoff, Boris" uniqKey="Winterhoff B" first="Boris" last="Winterhoff">Boris Winterhoff</name><affiliation><nlm:aff id="A109">Department of Obstetrics and Gynecology, Mayo Clinic, Rochester, MN, USA, 55905</nlm:aff></affiliation></author><author><name sortKey="Woo, Yin Ling" sort="Woo, Yin Ling" uniqKey="Woo Y" first="Yin Ling" last="Woo">Yin Ling Woo</name><affiliation><nlm:aff id="A77">Department of Obstetrics and Gynaecology, University Malaya Medical Centre, University Malaya, 59100 Kuala Lumpur, Federal Territory of Kuala Lumpur, Malaysia</nlm:aff></affiliation></author><author><name sortKey="Wu, Anna H" sort="Wu, Anna H" uniqKey="Wu A" first="Anna H." last="Wu">Anna H. Wu</name><affiliation><nlm:aff id="A2">Department of Preventive Medicine, Keck School of Medicine, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA, USA, 90033</nlm:aff></affiliation></author><author><name sortKey="Xiang, Yong Bing" sort="Xiang, Yong Bing" uniqKey="Xiang Y" first="Yong-Bing" last="Xiang">Yong-Bing Xiang</name><affiliation><nlm:aff id="A110">Shanghai Cancer Institute, Shanghai, China, 2200-25</nlm:aff></affiliation></author><author><name sortKey="Yang, Hannah P" sort="Yang, Hannah P" uniqKey="Yang H" first="Hannah P." last="Yang">Hannah P. Yang</name><affiliation><nlm:aff id="A22">Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda MD, USA, 20892</nlm:aff></affiliation></author><author><name sortKey="Zheng, Wei" sort="Zheng, Wei" uniqKey="Zheng W" first="Wei" last="Zheng">Wei Zheng</name><affiliation><nlm:aff id="A27">Vanderbilt Epidemiology Center and Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN, USA, 37232</nlm:aff></affiliation></author><author><name sortKey="Ziogas, Argyrios" sort="Ziogas, Argyrios" uniqKey="Ziogas A" first="Argyrios" last="Ziogas">Argyrios Ziogas</name><affiliation><nlm:aff id="A111">Department of Epidemiology, Center for Cancer Genetics Research and Prevention, School of Medicine, University of California Irvine, Irvine, California, USA, 92697</nlm:aff></affiliation></author><author><name sortKey="Zulkifli, Famida" sort="Zulkifli, Famida" uniqKey="Zulkifli F" first="Famida" last="Zulkifli">Famida Zulkifli</name><affiliation><nlm:aff id="A77">Department of Obstetrics and Gynaecology, University Malaya Medical Centre, University Malaya, 59100 Kuala Lumpur, Federal Territory of Kuala Lumpur, Malaysia</nlm:aff></affiliation></author><author><name sortKey="Phelan, Catherine M" sort="Phelan, Catherine M" uniqKey="Phelan C" first="Catherine M." last="Phelan">Catherine M. Phelan</name><affiliation><nlm:aff id="A1">Department of Cancer Epidemiology, Division of Population Sciences, Moffitt Cancer Center, Tampa, FL, USA, 33612</nlm:aff></affiliation></author><author><name sortKey="Iversen, Edwin" sort="Iversen, Edwin" uniqKey="Iversen E" first="Edwin" last="Iversen">Edwin Iversen</name><affiliation><nlm:aff id="A112">Department of Statistical Science, Duke University, Durham, NC, USA, 27708</nlm:aff></affiliation></author><author><name sortKey="Schildkraut, Joellen M" sort="Schildkraut, Joellen M" uniqKey="Schildkraut J" first="Joellen M." last="Schildkraut">Joellen M. Schildkraut</name><affiliation><nlm:aff id="A108">Department of Community and Family Medicine, Duke University Medical Center, Durham, NC, USA, 27708</nlm:aff></affiliation><affiliation><nlm:aff id="A113">Cancer Prevention, Detection and Control Research Program, Duke Cancer Institute, Durham, North Carolina, USA, 27708-0251</nlm:aff></affiliation></author><author><name sortKey="Berchuck, Andrew" sort="Berchuck, Andrew" uniqKey="Berchuck A" first="Andrew" last="Berchuck">Andrew Berchuck</name><affiliation><nlm:aff id="A114">Department of Obstetrics and Gynecology, Duke Comprehensive Cancer Center, Durham, NC, USA, 27708</nlm:aff></affiliation></author><author><name sortKey="Fridley, Brooke L" sort="Fridley, Brooke L" uniqKey="Fridley B" first="Brooke L." last="Fridley">Brooke L. Fridley</name><affiliation><nlm:aff id="A115">Department of Biostatistics, University of Kansas Medical Center, Kansas City, KS, USA, 66160</nlm:aff></affiliation></author><author><name sortKey="Goode, Ellen L" sort="Goode, Ellen L" uniqKey="Goode E" first="Ellen L." last="Goode">Ellen L. Goode</name><affiliation><nlm:aff id="A31">Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, MN, USA, 55905</nlm:aff></affiliation></author><author><name sortKey="Pharoah, Paul D P" sort="Pharoah, Paul D P" uniqKey="Pharoah P" first="Paul D. P." last="Pharoah">Paul D. P. Pharoah</name><affiliation><nlm:aff id="A11">Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, CB1 8RN, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A43">Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, CB1 8RN, UK</nlm:aff></affiliation></author><author><name sortKey="Monteiro, Alvaro N A" sort="Monteiro, Alvaro N A" uniqKey="Monteiro A" first="Alvaro N. A." last="Monteiro">Alvaro N. A. Monteiro</name><affiliation><nlm:aff id="A1">Department of Cancer Epidemiology, Division of Population Sciences, Moffitt Cancer Center, Tampa, FL, USA, 33612</nlm:aff></affiliation></author><author><name sortKey="Sellers, Thomas A" sort="Sellers, Thomas A" uniqKey="Sellers T" first="Thomas A." last="Sellers">Thomas A. Sellers</name><affiliation><nlm:aff id="A1">Department of Cancer Epidemiology, Division of Population Sciences, Moffitt Cancer Center, Tampa, FL, USA, 33612</nlm:aff></affiliation></author><author><name sortKey="Gayther, Simon A" sort="Gayther, Simon A" uniqKey="Gayther S" first="Simon A." last="Gayther">Simon A. 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Shen</name><affiliation><nlm:aff id="A2">Department of Preventive Medicine, Keck School of Medicine, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA, USA, 90033</nlm:aff></affiliation></author><author><name sortKey="Velkova, Aneliya" sort="Velkova, Aneliya" uniqKey="Velkova A" first="Aneliya" last="Velkova">Aneliya Velkova</name><affiliation><nlm:aff id="A1">Department of Cancer Epidemiology, Division of Population Sciences, Moffitt Cancer Center, Tampa, FL, USA, 33612</nlm:aff></affiliation></author><author><name sortKey="Tyrer, Jonathan P" sort="Tyrer, Jonathan P" uniqKey="Tyrer J" first="Jonathan P." last="Tyrer">Jonathan P. Tyrer</name><affiliation><nlm:aff id="A3">Department of Oncology, University of Cambridge, Cambridge, CB1 8RN, UK</nlm:aff></affiliation></author><author><name sortKey="Chen, Zhihua" sort="Chen, Zhihua" uniqKey="Chen Z" first="Zhihua" last="Chen">Zhihua Chen</name><affiliation><nlm:aff id="A4">Department of Biomedical Informatics, Moffitt Cancer Center, Tampa, FL, USA, 33612</nlm:aff></affiliation></author><author><name sortKey="Lin, Hui Yi" sort="Lin, Hui Yi" uniqKey="Lin H" first="Hui-Yi" last="Lin">Hui-Yi Lin</name><affiliation><nlm:aff id="A5">Department of Biostatistics, Moffitt Cancer Center, Tampa, FL, USA, 33612</nlm:aff></affiliation></author><author><name sortKey="Chen, Y Ann" sort="Chen, Y Ann" uniqKey="Chen Y" first="Y. Ann" last="Chen">Y. Ann Chen</name><affiliation><nlm:aff id="A5">Department of Biostatistics, Moffitt Cancer Center, Tampa, FL, USA, 33612</nlm:aff></affiliation></author><author><name sortKey="Tsai, Ya Yu" sort="Tsai, Ya Yu" uniqKey="Tsai Y" first="Ya-Yu" last="Tsai">Ya-Yu Tsai</name><affiliation><nlm:aff id="A1">Department of Cancer Epidemiology, Division of Population Sciences, Moffitt Cancer Center, Tampa, FL, USA, 33612</nlm:aff></affiliation></author><author><name sortKey="Qu, Xiaotao" sort="Qu, Xiaotao" uniqKey="Qu X" first="Xiaotao" last="Qu">Xiaotao Qu</name><affiliation><nlm:aff id="A4">Department of Biomedical Informatics, Moffitt Cancer Center, Tampa, FL, USA, 33612</nlm:aff></affiliation></author><author><name sortKey="Ramus, Susan J" sort="Ramus, Susan J" uniqKey="Ramus S" first="Susan J." last="Ramus">Susan J. Ramus</name><affiliation><nlm:aff id="A2">Department of Preventive Medicine, Keck School of Medicine, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA, USA, 90033</nlm:aff></affiliation></author><author><name sortKey="Karevan, Rod" sort="Karevan, Rod" uniqKey="Karevan R" first="Rod" last="Karevan">Rod Karevan</name><affiliation><nlm:aff id="A2">Department of Preventive Medicine, Keck School of Medicine, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA, USA, 90033</nlm:aff></affiliation></author><author><name sortKey="Lee, Janet" sort="Lee, Janet" uniqKey="Lee J" first="Janet" last="Lee">Janet Lee</name><affiliation><nlm:aff id="A2">Department of Preventive Medicine, Keck School of Medicine, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA, USA, 90033</nlm:aff></affiliation></author><author><name sortKey="Lee, Nathan" sort="Lee, Nathan" uniqKey="Lee N" first="Nathan" last="Lee">Nathan Lee</name><affiliation><nlm:aff id="A2">Department of Preventive Medicine, Keck School of Medicine, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA, USA, 90033</nlm:aff></affiliation></author><author><name sortKey="Larson, Melissa C" sort="Larson, Melissa C" uniqKey="Larson M" first="Melissa C." last="Larson">Melissa C. Larson</name><affiliation><nlm:aff id="A6">Department of Health Science Research, Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN, USA, 55905</nlm:aff></affiliation></author><author><name sortKey="Aben, Katja K" sort="Aben, Katja K" uniqKey="Aben K" first="Katja K." last="Aben">Katja K. Aben</name><affiliation><nlm:aff id="A7">Department of Epidemiology, Biostatistics and HTA, Radboud University Medical Centre, Nijmegen, HB 6500, Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A8">Comprehensive Cancer Center, the Netherlands, Utrecht, Amsterdam, 1066CX, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Anton Culver, Hoda" sort="Anton Culver, Hoda" uniqKey="Anton Culver H" first="Hoda" last="Anton-Culver">Hoda Anton-Culver</name><affiliation><nlm:aff id="A9">Department of Epidemiology, Director of Genetic Epidemiology Research Institute, UCI Center of Medicine, University of California Irvine, Irvine, CA, USA, 92697</nlm:aff></affiliation></author><author><name sortKey="Antonenkova, Natalia" sort="Antonenkova, Natalia" uniqKey="Antonenkova N" first="Natalia" last="Antonenkova">Natalia Antonenkova</name><affiliation><nlm:aff id="A10">Byelorussian Institute for Oncology and Medical Radiology Aleksandrov N.N., 223040, Minsk, Belarus</nlm:aff></affiliation></author><author><name sortKey="Antoniou, Antonis" sort="Antoniou, Antonis" uniqKey="Antoniou A" first="Antonis" last="Antoniou">Antonis Antoniou</name><affiliation><nlm:aff id="A11">Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, CB1 8RN, UK</nlm:aff></affiliation></author><author><name sortKey="Armasu, Sebastian M" sort="Armasu, Sebastian M" uniqKey="Armasu S" first="Sebastian M." last="Armasu">Sebastian M. Armasu</name><affiliation><nlm:aff id="A6">Department of Health Science Research, Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN, USA, 55905</nlm:aff></affiliation></author><author><name sortKey="Bacot, Francois" sort="Bacot, Francois" uniqKey="Bacot F" first="François" last="Bacot">François Bacot</name><affiliation><nlm:aff id="A14">McGill University and Génome Québec Innovation Centre, Montréal (Québec) Canada, H3A 0G1</nlm:aff></affiliation></author><author><name sortKey="Baglietto, Laura" sort="Baglietto, Laura" uniqKey="Baglietto L" first="Laura" last="Baglietto">Laura Baglietto</name><affiliation><nlm:aff id="A15">Cancer Epidemiology Centre, The Cancer Council Victoria, Melbourne, Carlton VIC 3053, Australia</nlm:aff></affiliation><affiliation><nlm:aff id="A16">Centre for Molecular, Environmental, Genetic and Analytical Epidemiology, University of Melbourne, Melbourne, VIC 3010, Australia</nlm:aff></affiliation></author><author><name sortKey="Bandera, Elisa V" sort="Bandera, Elisa V" uniqKey="Bandera E" first="Elisa V." last="Bandera">Elisa V. Bandera</name><affiliation><nlm:aff id="A17">The Cancer Institute of New Jersey, Robert Wood Johnson Medical School, New Brunswick, NJ, USA, 08901</nlm:aff></affiliation></author><author><name sortKey="Barnholtz Sloan, Jill" sort="Barnholtz Sloan, Jill" uniqKey="Barnholtz Sloan J" first="Jill" last="Barnholtz-Sloan">Jill Barnholtz-Sloan</name><affiliation><nlm:aff id="A18">Case Comprehensive Cancer Center, Case Western Reserve University School of Medicine, Cleveland, OH, USA, 44195</nlm:aff></affiliation></author><author><name sortKey="Beckmann, Matthias W" sort="Beckmann, Matthias W" uniqKey="Beckmann M" first="Matthias W." last="Beckmann">Matthias W. Beckmann</name><affiliation><nlm:aff id="A19">University Hospital Erlangen, Department of Gynecology and Obstetrics, Friedrich-Alexander-University Erlangen-Nuremberg, Comprehensive Cancer Center, Erlangen, 91054, Germany</nlm:aff></affiliation></author><author><name sortKey="Birrer, Michael J" sort="Birrer, Michael J" uniqKey="Birrer M" first="Michael J." last="Birrer">Michael J. Birrer</name><affiliation><nlm:aff id="A20">Massachusetts General Hospital, Boston, MA, USA, 02114</nlm:aff></affiliation></author><author><name sortKey="Bloom, Greg" sort="Bloom, Greg" uniqKey="Bloom G" first="Greg" last="Bloom">Greg Bloom</name><affiliation><nlm:aff id="A4">Department of Biomedical Informatics, Moffitt Cancer Center, Tampa, FL, USA, 33612</nlm:aff></affiliation></author><author><name sortKey="Bogdanova, Natalia" sort="Bogdanova, Natalia" uniqKey="Bogdanova N" first="Natalia" last="Bogdanova">Natalia Bogdanova</name><affiliation><nlm:aff id="A21">Gynaecology Research Unit, Hannover Medical School, Hannover, 30625, Germany</nlm:aff></affiliation></author><author><name sortKey="Brinton, Louise A" sort="Brinton, Louise A" uniqKey="Brinton L" first="Louise A." last="Brinton">Louise A. Brinton</name><affiliation><nlm:aff id="A22">Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda MD, USA, 20892</nlm:aff></affiliation></author><author><name sortKey="Brooks Wilson, Angela" sort="Brooks Wilson, Angela" uniqKey="Brooks Wilson A" first="Angela" last="Brooks-Wilson">Angela Brooks-Wilson</name><affiliation><nlm:aff id="A23">Genome Sciences Centre, BC Cancer Agency, Vancouver, BC, Canada, V5Z 1L3</nlm:aff></affiliation></author><author><name sortKey="Brown, Robert" sort="Brown, Robert" uniqKey="Brown R" first="Robert" last="Brown">Robert Brown</name><affiliation><nlm:aff id="A24">Department of Surgery and Cancer, Imperial College London, London, SW7 2AZ, UK</nlm:aff></affiliation></author><author><name sortKey="Butzow, Ralf" sort="Butzow, Ralf" uniqKey="Butzow R" first="Ralf" last="Butzow">Ralf Butzow</name><affiliation><nlm:aff id="A25">Department of Pathology, Helsinki University Central Hospital, Helsinki, Finland, 00530</nlm:aff></affiliation><affiliation><nlm:aff id="A26">Department of Obstetrics and Gynecology, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland, 00530</nlm:aff></affiliation></author><author><name sortKey="Cai, Qiuyin" sort="Cai, Qiuyin" uniqKey="Cai Q" first="Qiuyin" last="Cai">Qiuyin Cai</name><affiliation><nlm:aff id="A27">Vanderbilt Epidemiology Center and Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN, USA, 37232</nlm:aff></affiliation></author><author><name sortKey="Campbell, Ian" sort="Campbell, Ian" uniqKey="Campbell I" first="Ian" last="Campbell">Ian Campbell</name><affiliation><nlm:aff id="A13">Cancer Genetics Laboratory, Research Division, Peter MacCallum Cancer Centre, Melbourne, VIC 3002, Australia</nlm:aff></affiliation><affiliation><nlm:aff id="A28">Department of Pathology, University of Melbourne, Parkville, VIC 3053, Australia</nlm:aff></affiliation></author><author><name sortKey="Chang Claude, Jenny" sort="Chang Claude, Jenny" uniqKey="Chang Claude J" first="Jenny" last="Chang-Claude">Jenny Chang-Claude</name><affiliation><nlm:aff id="A29">German Cancer Research Center, Division of Cancer Epidemiology, 69120, Heidelberg, Germany</nlm:aff></affiliation></author><author><name sortKey="Chanock, Stephen" sort="Chanock, Stephen" uniqKey="Chanock S" first="Stephen" last="Chanock">Stephen Chanock</name><affiliation><nlm:aff id="A22">Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda MD, USA, 20892</nlm:aff></affiliation></author><author><name sortKey="Chenevix Trench, Georgia" sort="Chenevix Trench, Georgia" uniqKey="Chenevix Trench G" first="Georgia" last="Chenevix-Trench">Georgia Chenevix-Trench</name><affiliation><nlm:aff id="A12">Queensland Institute of Medical Research, Brisbane QLD 4006, Australia</nlm:aff></affiliation></author><author><name sortKey="Cheng, Jin Q" sort="Cheng, Jin Q" uniqKey="Cheng J" first="Jin Q." last="Cheng">Jin Q. Cheng</name><affiliation><nlm:aff id="A30">Department of Interdisciplinary Oncology, Moffitt Cancer Center, Tampa, FL, USA, 33612</nlm:aff></affiliation></author><author><name sortKey="Cicek, Mine S" sort="Cicek, Mine S" uniqKey="Cicek M" first="Mine S." last="Cicek">Mine S. Cicek</name><affiliation><nlm:aff id="A31">Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, MN, USA, 55905</nlm:aff></affiliation></author><author><name sortKey="Coetzee, Gerhard A" sort="Coetzee, Gerhard A" uniqKey="Coetzee G" first="Gerhard A." last="Coetzee">Gerhard A. Coetzee</name><affiliation><nlm:aff id="A32">Department of Urology, Microbiology and Preventive Medicine, University of Southern California, Norris Comprehensive Cancer Center, Los Angeles, CA, USA, 90089</nlm:aff></affiliation></author><author><name sortKey="Cook, Linda S" sort="Cook, Linda S" uniqKey="Cook L" first="Linda S." last="Cook">Linda S. Cook</name><affiliation><nlm:aff id="A35">Division Epidemiology and Biostatistics, University of New Mexico, Albuquerque, NM, USA, 87131</nlm:aff></affiliation></author><author><name sortKey="Couch, Fergus J" sort="Couch, Fergus J" uniqKey="Couch F" first="Fergus J." last="Couch">Fergus J. Couch</name><affiliation><nlm:aff id="A34">Department of Laboratory of Medicine and Pathology, Mayo Clinic, Rochester, MN, USA, 55905</nlm:aff></affiliation></author><author><name sortKey="Cramer, Daniel W" sort="Cramer, Daniel W" uniqKey="Cramer D" first="Daniel W." last="Cramer">Daniel W. Cramer</name><affiliation><nlm:aff id="A36">Obstetrics and Gynecology Epidemiology Center, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA, 02115</nlm:aff></affiliation></author><author><name sortKey="Cunningham, Julie M" sort="Cunningham, Julie M" uniqKey="Cunningham J" first="Julie M." last="Cunningham">Julie M. Cunningham</name><affiliation><nlm:aff id="A31">Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, MN, USA, 55905</nlm:aff></affiliation></author><author><name sortKey="Dansonka Mieszkowska, Agnieszka" sort="Dansonka Mieszkowska, Agnieszka" uniqKey="Dansonka Mieszkowska A" first="Agnieszka" last="Dansonka-Mieszkowska">Agnieszka Dansonka-Mieszkowska</name><affiliation><nlm:aff id="A37">Department of Molecular Pathology, The Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland, 02-781</nlm:aff></affiliation></author><author><name sortKey="Despierre, Evelyn" sort="Despierre, Evelyn" uniqKey="Despierre E" first="Evelyn" last="Despierre">Evelyn Despierre</name><affiliation><nlm:aff id="A38">Division of Gynecologic Oncology, Department of Obstetrics and Gynaecology and Leuven Cancer Institute, University Hospitals Leuven, Leuven, Belgium, 3000</nlm:aff></affiliation></author><author><name sortKey="Doherty, Jennifer A" sort="Doherty, Jennifer A" uniqKey="Doherty J" first="Jennifer A" last="Doherty">Jennifer A. Doherty</name><affiliation><nlm:aff id="A39">Section of Biostatistics and Epidemiology, The Geisel School of Medicine at Dartmouth, Lebanon, NH, USA, 03755</nlm:aff></affiliation></author><author><name sortKey="Dork, Thilo" sort="Dork, Thilo" uniqKey="Dork T" first="Thilo" last="Dörk">Thilo Dörk</name><affiliation><nlm:aff id="A21">Gynaecology Research Unit, Hannover Medical School, Hannover, 30625, Germany</nlm:aff></affiliation></author><author><name sortKey="Du Bois, Andreas" sort="Du Bois, Andreas" uniqKey="Du Bois A" first="Andreas" last="Du Bois">Andreas Du Bois</name><affiliation><nlm:aff id="A40">Department of Gynecology and Gynecologic Oncology, Dr. Horst Schmidt Klinik Wiesbaden, 65199, Wiesbaden, Germany</nlm:aff></affiliation><affiliation><nlm:aff id="A41">Department of Gynecology and Gynecologic Oncology, Kliniken Essen-Mitte, 45136, Essen, Germany</nlm:aff></affiliation></author><author><name sortKey="Durst, Matthias" sort="Durst, Matthias" uniqKey="Durst M" first="Matthias" last="Dürst">Matthias Dürst</name><affiliation><nlm:aff id="A42">Department of Gynecology and Obstetrics, Jena University Hospital, 07743, Jena, Germany</nlm:aff></affiliation></author><author><name sortKey="Easton, Douglas F" sort="Easton, Douglas F" uniqKey="Easton D" first="Douglas F" last="Easton">Douglas F. Easton</name><affiliation><nlm:aff id="A11">Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, CB1 8RN, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A43">Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, CB1 8RN, UK</nlm:aff></affiliation></author><author><name sortKey="Eccles, Diana" sort="Eccles, Diana" uniqKey="Eccles D" first="Diana" last="Eccles">Diana Eccles</name><affiliation><nlm:aff id="A44">Faculty of Medicine, University of Southampton, University Hospital Southampton, SO17 1BJ, UK</nlm:aff></affiliation></author><author><name sortKey="Edwards, Robert" sort="Edwards, Robert" uniqKey="Edwards R" first="Robert" last="Edwards">Robert Edwards</name><affiliation><nlm:aff id="A45">Maggee Women's Hospital, Pittsburg, PA, USA, 15213</nlm:aff></affiliation></author><author><name sortKey="Ekici, Arif B" sort="Ekici, Arif B" uniqKey="Ekici A" first="Arif B." last="Ekici">Arif B. Ekici</name><affiliation><nlm:aff id="A46">Institute of Human Genetics, Friedrich-Alexander-University Erlangen-Nuremberg, 91054, Erlangen, Germany</nlm:aff></affiliation></author><author><name sortKey="Fasching, Peter A" sort="Fasching, Peter A" uniqKey="Fasching P" first="Peter A." last="Fasching">Peter A. Fasching</name><affiliation><nlm:aff id="A19">University Hospital Erlangen, Department of Gynecology and Obstetrics, Friedrich-Alexander-University Erlangen-Nuremberg, Comprehensive Cancer Center, Erlangen, 91054, Germany</nlm:aff></affiliation><affiliation><nlm:aff id="A47">Department of Medicine, Division of Hematology and Oncology, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, USA, 90095</nlm:aff></affiliation></author><author><name sortKey="Fenstermacher, David A" sort="Fenstermacher, David A" uniqKey="Fenstermacher D" first="David A." last="Fenstermacher">David A. Fenstermacher</name><affiliation><nlm:aff id="A4">Department of Biomedical Informatics, Moffitt Cancer Center, Tampa, FL, USA, 33612</nlm:aff></affiliation></author><author><name sortKey="Flanagan, James M" sort="Flanagan, James M" uniqKey="Flanagan J" first="James M." last="Flanagan">James M. Flanagan</name><affiliation><nlm:aff id="A24">Department of Surgery and Cancer, Imperial College London, London, SW7 2AZ, UK</nlm:aff></affiliation></author><author><name sortKey="Garcia Closas, Montserrat" sort="Garcia Closas, Montserrat" uniqKey="Garcia Closas M" first="Montserrat" last="Garcia-Closas">Montserrat Garcia-Closas</name><affiliation><nlm:aff id="A48">Sections of Epidemiology and Genetics at the Institute of Cancer Research and Breakthrough Breast Cancer Research Centre, London, UK, SW7 3RP</nlm:aff></affiliation></author><author><name sortKey="Gentry Maharaj, Aleksandra" sort="Gentry Maharaj, Aleksandra" uniqKey="Gentry Maharaj A" first="Aleksandra" last="Gentry-Maharaj">Aleksandra Gentry-Maharaj</name><affiliation><nlm:aff id="A49">Gynaecological Cancer Research Centre, UCL EGA Institute for Women's Health, London, NW1 2BU, United Kingdom</nlm:aff></affiliation></author><author><name sortKey="Giles, Graham G" sort="Giles, Graham G" uniqKey="Giles G" first="Graham G." last="Giles">Graham G. Giles</name><affiliation><nlm:aff id="A15">Cancer Epidemiology Centre, The Cancer Council Victoria, Melbourne, Carlton VIC 3053, Australia</nlm:aff></affiliation><affiliation><nlm:aff id="A16">Centre for Molecular, Environmental, Genetic and Analytical Epidemiology, University of Melbourne, Melbourne, VIC 3010, Australia</nlm:aff></affiliation><affiliation><nlm:aff id="A50">Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, VIC 3806, Australia</nlm:aff></affiliation></author><author><name sortKey="Glasspool, Rosalind M" sort="Glasspool, Rosalind M" uniqKey="Glasspool R" first="Rosalind M." last="Glasspool">Rosalind M. Glasspool</name><affiliation><nlm:aff id="A51">The Beatson West of Scotland Cancer Centre, Glasgow, G12 0YN, UK</nlm:aff></affiliation></author><author><name sortKey="Gonzalez Bosquet, Jesus" sort="Gonzalez Bosquet, Jesus" uniqKey="Gonzalez Bosquet J" first="Jesus" last="Gonzalez-Bosquet">Jesus Gonzalez-Bosquet</name><affiliation><nlm:aff id="A52">Department of Women's Oncology, Moffitt Cancer Center, Tampa, FL, USA, 33612</nlm:aff></affiliation></author><author><name sortKey="Goodman, Marc T" sort="Goodman, Marc T" uniqKey="Goodman M" first="Marc T." last="Goodman">Marc T. Goodman</name><affiliation><nlm:aff id="A53">Samuel Oschin Comprehensive Cancer Center Institute, Cedars Sinai Medical Center, Los Angeles, CA, USA, 90048</nlm:aff></affiliation></author><author><name sortKey="Gore, Martin" sort="Gore, Martin" uniqKey="Gore M" first="Martin" last="Gore">Martin Gore</name><affiliation><nlm:aff id="A54">Gynecological Oncology Unit, The Royal Marsden Hospital, London, SW3 6JJ, United Kingdom</nlm:aff></affiliation></author><author><name sortKey="G Rski, Bohdan" sort="G Rski, Bohdan" uniqKey="G Rski B" first="Bohdan" last="G Rski">Bohdan G Rski</name><affiliation><nlm:aff id="A55">International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland, 70-115</nlm:aff></affiliation></author><author><name sortKey="Gronwald, Jacek" sort="Gronwald, Jacek" uniqKey="Gronwald J" first="Jacek" last="Gronwald">Jacek Gronwald</name><affiliation><nlm:aff id="A55">International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland, 70-115</nlm:aff></affiliation></author><author><name sortKey="Hall, Per" sort="Hall, Per" uniqKey="Hall P" first="Per" last="Hall">Per Hall</name><affiliation><nlm:aff id="A56">Department of Epidemiology and Biostatistics, Karolinska Istitutet, Stockholm, Sweden, 171-77</nlm:aff></affiliation></author><author><name sortKey="Halle, Mari K" sort="Halle, Mari K" uniqKey="Halle M" first="Mari K." last="Halle">Mari K. Halle</name><affiliation><nlm:aff id="A57">Department of Gynecology and Obstetrics, Haukeland University Hospital, Bergen, HB 5006, Norway</nlm:aff></affiliation><affiliation><nlm:aff id="A58">Department of Clinical Medicine, University of Bergen, 5006, Bergen, Norway</nlm:aff></affiliation></author><author><name sortKey="Harter, Philipp" sort="Harter, Philipp" uniqKey="Harter P" first="Philipp" last="Harter">Philipp Harter</name><affiliation><nlm:aff id="A40">Department of Gynecology and Gynecologic Oncology, Dr. Horst Schmidt Klinik Wiesbaden, 65199, Wiesbaden, Germany</nlm:aff></affiliation><affiliation><nlm:aff id="A41">Department of Gynecology and Gynecologic Oncology, Kliniken Essen-Mitte, 45136, Essen, Germany</nlm:aff></affiliation></author><author><name sortKey="Heitz, Florian" sort="Heitz, Florian" uniqKey="Heitz F" first="Florian" last="Heitz">Florian Heitz</name><affiliation><nlm:aff id="A40">Department of Gynecology and Gynecologic Oncology, Dr. Horst Schmidt Klinik Wiesbaden, 65199, Wiesbaden, Germany</nlm:aff></affiliation><affiliation><nlm:aff id="A41">Department of Gynecology and Gynecologic Oncology, Kliniken Essen-Mitte, 45136, Essen, Germany</nlm:aff></affiliation></author><author><name sortKey="Hillemanns, Peter" sort="Hillemanns, Peter" uniqKey="Hillemanns P" first="Peter" last="Hillemanns">Peter Hillemanns</name><affiliation><nlm:aff id="A59">Clinics of Obstetrics and Gynaecology, Hannover Medical School, 30625, Hannover, Germany</nlm:aff></affiliation></author><author><name sortKey="Hoatlin, Maureen" sort="Hoatlin, Maureen" uniqKey="Hoatlin M" first="Maureen" last="Hoatlin">Maureen Hoatlin</name><affiliation><nlm:aff id="A60">Department of Biochemistry and Molecular Biology, Oregon Health and Science University, Portland, OR, USA, 97239</nlm:aff></affiliation></author><author><name sortKey="H Gdall, Claus K" sort="H Gdall, Claus K" uniqKey="H Gdall C" first="Claus K." last="H Gdall">Claus K. H Gdall</name><affiliation><nlm:aff id="A61">The Juliane Marie Centre, Department of Obstetrics and Gynecology, Rigshospitalet, Copenhagen, 2100, Denmark</nlm:aff></affiliation></author><author><name sortKey="H Gdall, Estrid" sort="H Gdall, Estrid" uniqKey="H Gdall E" first="Estrid" last="H Gdall">Estrid H Gdall</name><affiliation><nlm:aff id="A62">Department of Pathology, Molecular Unit, Herlev Hospital, University of Copenhagen, Denmark, 2730</nlm:aff></affiliation><affiliation><nlm:aff id="A63">Virus, Lifestyle and Genes, Danish Cancer Society Research Center, DK-2100, Copenhagen, Denmark</nlm:aff></affiliation></author><author><name sortKey="Hosono, Satoyo" sort="Hosono, Satoyo" uniqKey="Hosono S" first="Satoyo" last="Hosono">Satoyo Hosono</name><affiliation><nlm:aff id="A64">Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya, Aichi, 464-8681, Japan</nlm:aff></affiliation></author><author><name sortKey="Jakubowska, Anna" sort="Jakubowska, Anna" uniqKey="Jakubowska A" first="Anna" last="Jakubowska">Anna Jakubowska</name><affiliation><nlm:aff id="A55">International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland, 70-115</nlm:aff></affiliation></author><author><name sortKey="Jensen, Allan" sort="Jensen, Allan" uniqKey="Jensen A" first="Allan" last="Jensen">Allan Jensen</name><affiliation><nlm:aff id="A63">Virus, Lifestyle and Genes, Danish Cancer Society Research Center, DK-2100, Copenhagen, Denmark</nlm:aff></affiliation></author><author><name sortKey="Jim, Heather" sort="Jim, Heather" uniqKey="Jim H" first="Heather" last="Jim">Heather Jim</name><affiliation><nlm:aff id="A65">Department of Health Outcomes and Behavior, Moffitt Cancer Center, Tampa, FL, USA, 33612</nlm:aff></affiliation></author><author><name sortKey="Kalli, Kimberly R" sort="Kalli, Kimberly R" uniqKey="Kalli K" first="Kimberly R." last="Kalli">Kimberly R. Kalli</name><affiliation><nlm:aff id="A66">Department of Medical Oncology, Mayo Clinic, Rochester, MN, USA, 55905</nlm:aff></affiliation></author><author><name sortKey="Karlan, Beth Y" sort="Karlan, Beth Y" uniqKey="Karlan B" first="Beth Y." last="Karlan">Beth Y. Karlan</name><affiliation><nlm:aff id="A67">Women's Cancer Program at the Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA, 90048</nlm:aff></affiliation></author><author><name sortKey="Kaye, Stanley B" sort="Kaye, Stanley B" uniqKey="Kaye S" first="Stanley B." last="Kaye">Stanley B. Kaye</name><affiliation><nlm:aff id="A68">Section of Medicine, Institute of Cancer Research, Sutton, SM2 5NG, UK</nlm:aff></affiliation></author><author><name sortKey="Kelemen, Linda E" sort="Kelemen, Linda E" uniqKey="Kelemen L" first="Linda E." last="Kelemen">Linda E. Kelemen</name><affiliation><nlm:aff id="A69">Department of Popluation Health Research, Alberta Health Services-Cancer Care, Calgary, Alberta, Canada and Departments of Medical Genetics and Oncology, University of Calgary, Calgary, AB, Canada, T2N 2T9</nlm:aff></affiliation></author><author><name sortKey="Kiemeney, Lambertus A" sort="Kiemeney, Lambertus A" uniqKey="Kiemeney L" first="Lambertus A." last="Kiemeney">Lambertus A. Kiemeney</name><affiliation><nlm:aff id="A7">Department of Epidemiology, Biostatistics and HTA, Radboud University Medical Centre, Nijmegen, HB 6500, Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A8">Comprehensive Cancer Center, the Netherlands, Utrecht, Amsterdam, 1066CX, The Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A70">Department of Urology, Radboud University Medical Centre, Nijmegen, HB 6500, Netherlands</nlm:aff></affiliation></author><author><name sortKey="Kikkawa, Fumitaka" sort="Kikkawa, Fumitaka" uniqKey="Kikkawa F" first="Fumitaka" last="Kikkawa">Fumitaka Kikkawa</name><affiliation><nlm:aff id="A71">Department of Obsterics and Gynecology, Nagoya University Graduate School of Medicine, Nagoya, Aichi, 466-8550, Japan</nlm:aff></affiliation></author><author><name sortKey="Konecny, Gottfried E" sort="Konecny, Gottfried E" uniqKey="Konecny G" first="Gottfried E." last="Konecny">Gottfried E. Konecny</name><affiliation><nlm:aff id="A47">Department of Medicine, Division of Hematology and Oncology, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, USA, 90095</nlm:aff></affiliation></author><author><name sortKey="Krakstad, Camilla" sort="Krakstad, Camilla" uniqKey="Krakstad C" first="Camilla" last="Krakstad">Camilla Krakstad</name><affiliation><nlm:aff id="A57">Department of Gynecology and Obstetrics, Haukeland University Hospital, Bergen, HB 5006, Norway</nlm:aff></affiliation><affiliation><nlm:aff id="A58">Department of Clinical Medicine, University of Bergen, 5006, Bergen, Norway</nlm:aff></affiliation></author><author><name sortKey="Kjaer, Susanne Kruger" sort="Kjaer, Susanne Kruger" uniqKey="Kjaer S" first="Susanne Krüger" last="Kjaer">Susanne Krüger Kjaer</name><affiliation><nlm:aff id="A61">The Juliane Marie Centre, Department of Obstetrics and Gynecology, Rigshospitalet, Copenhagen, 2100, Denmark</nlm:aff></affiliation><affiliation><nlm:aff id="A63">Virus, Lifestyle and Genes, Danish Cancer Society Research Center, DK-2100, Copenhagen, Denmark</nlm:aff></affiliation></author><author><name sortKey="Kupryjanczyk, Jolanta" sort="Kupryjanczyk, Jolanta" uniqKey="Kupryjanczyk J" first="Jolanta" last="Kupryjanczyk">Jolanta Kupryjanczyk</name><affiliation><nlm:aff id="A37">Department of Molecular Pathology, The Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland, 02-781</nlm:aff></affiliation></author><author><name sortKey="Lambrechts, Diether" sort="Lambrechts, Diether" uniqKey="Lambrechts D" first="Diether" last="Lambrechts">Diether Lambrechts</name><affiliation><nlm:aff id="A72">Vesalius Research Center, VIB, 3000, Leuven, Belgium</nlm:aff></affiliation><affiliation><nlm:aff id="A73">Laboratory for Translational Genetics, Department of Oncology, University of Leuven, 3000, Leuven, Belgium</nlm:aff></affiliation></author><author><name sortKey="Lambrechts, Sandrina" sort="Lambrechts, Sandrina" uniqKey="Lambrechts S" first="Sandrina" last="Lambrechts">Sandrina Lambrechts</name><affiliation><nlm:aff id="A38">Division of Gynecologic Oncology, Department of Obstetrics and Gynaecology and Leuven Cancer Institute, University Hospitals Leuven, Leuven, Belgium, 3000</nlm:aff></affiliation></author><author><name sortKey="Lancaster, Johnathan M" sort="Lancaster, Johnathan M" uniqKey="Lancaster J" first="Johnathan M." last="Lancaster">Johnathan M. Lancaster</name><affiliation><nlm:aff id="A52">Department of Women's Oncology, Moffitt Cancer Center, Tampa, FL, USA, 33612</nlm:aff></affiliation></author><author><name sortKey="Le, Nhu D" sort="Le, Nhu D" uniqKey="Le N" first="Nhu D." last="Le">Nhu D. Le</name><affiliation><nlm:aff id="A74">Cancer Control Research, BC Cancer Agency, Vancouver, BC, Canada, G12 0YN</nlm:aff></affiliation></author><author><name sortKey="Leminen, Arto" sort="Leminen, Arto" uniqKey="Leminen A" first="Arto" last="Leminen">Arto Leminen</name><affiliation><nlm:aff id="A26">Department of Obstetrics and Gynecology, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland, 00530</nlm:aff></affiliation></author><author><name sortKey="Levine, Douglas A" sort="Levine, Douglas A" uniqKey="Levine D" first="Douglas A." last="Levine">Douglas A. Levine</name><affiliation><nlm:aff id="A75">Gynecology Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY, USA, 10021</nlm:aff></affiliation></author><author><name sortKey="Liang, Dong" sort="Liang, Dong" uniqKey="Liang D" first="Dong" last="Liang">Dong Liang</name><affiliation><nlm:aff id="A76">College of Pharmacy and Health Sciences, Texas Southern University, Houston, Texas, USA, 77044</nlm:aff></affiliation></author><author><name sortKey="Lim, Boon Kiong" sort="Lim, Boon Kiong" uniqKey="Lim B" first="Boon Kiong" last="Lim">Boon Kiong Lim</name><affiliation><nlm:aff id="A77">Department of Obstetrics and Gynaecology, University Malaya Medical Centre, University Malaya, 59100 Kuala Lumpur, Federal Territory of Kuala Lumpur, Malaysia</nlm:aff></affiliation></author><author><name sortKey="Lin, Jie" sort="Lin, Jie" uniqKey="Lin J" first="Jie" last="Lin">Jie Lin</name><affiliation><nlm:aff id="A78">Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA, 77030</nlm:aff></affiliation></author><author><name sortKey="Lissowska, Jolanta" sort="Lissowska, Jolanta" uniqKey="Lissowska J" first="Jolanta" last="Lissowska">Jolanta Lissowska</name><affiliation><nlm:aff id="A79">Department of Cancer Epidemiology and Prevention, The Maria Sklodowska-Curie Memorial Cancer Center, 02-781, Warsaw, Poland</nlm:aff></affiliation></author><author><name sortKey="Lu, Karen H" sort="Lu, Karen H" uniqKey="Lu K" first="Karen H." last="Lu">Karen H. Lu</name><affiliation><nlm:aff id="A80">Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA, 77030</nlm:aff></affiliation></author><author><name sortKey="Lubi Ski, Jan" sort="Lubi Ski, Jan" uniqKey="Lubi Ski J" first="Jan" last="Lubi Ski">Jan Lubi Ski</name><affiliation><nlm:aff id="A55">International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland, 70-115</nlm:aff></affiliation></author><author><name sortKey="Lurie, Galina" sort="Lurie, Galina" uniqKey="Lurie G" first="Galina" last="Lurie">Galina Lurie</name><affiliation><nlm:aff id="A81">Cancer Epidemiology Program, University of Hawaii Cancer Center, Hawaii, USA, 96813</nlm:aff></affiliation></author><author><name sortKey="Massuger, Leon F A G" sort="Massuger, Leon F A G" uniqKey="Massuger L" first="Leon F. A. G." last="Massuger">Leon F. A. G. Massuger</name><affiliation><nlm:aff id="A82">Department of Gynaecology, Radboud University Medical Centre, Nijmegen, HB 6500, Netherlands</nlm:aff></affiliation></author><author><name sortKey="Matsuo, Keitaro" sort="Matsuo, Keitaro" uniqKey="Matsuo K" first="Keitaro" last="Matsuo">Keitaro Matsuo</name><affiliation><nlm:aff id="A64">Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya, Aichi, 464-8681, Japan</nlm:aff></affiliation></author><author><name sortKey="Mcguire, Valerie" sort="Mcguire, Valerie" uniqKey="Mcguire V" first="Valerie" last="Mcguire">Valerie Mcguire</name><affiliation><nlm:aff id="A83">Department of Health Research and Policy - Epidemiology, Stanford University School of Medicine, Stanford CA, USA, 94305</nlm:aff></affiliation></author><author><name sortKey="Mclaughlin, John R" sort="Mclaughlin, John R" uniqKey="Mclaughlin J" first="John R" last="Mclaughlin">John R. Mclaughlin</name><affiliation><nlm:aff id="A84">Dalla Lana School of Public Health, Faculty of Medicine, University of Toronto, ON, M5T 3M7, Canada</nlm:aff></affiliation><affiliation><nlm:aff id="A85">Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada, M5G 1X5</nlm:aff></affiliation></author><author><name sortKey="Menon, Usha" sort="Menon, Usha" uniqKey="Menon U" first="Usha" last="Menon">Usha Menon</name><affiliation><nlm:aff id="A49">Gynaecological Cancer Research Centre, UCL EGA Institute for Women's Health, London, NW1 2BU, United Kingdom</nlm:aff></affiliation></author><author><name sortKey="Modugno, Francesmary" sort="Modugno, Francesmary" uniqKey="Modugno F" first="Francesmary" last="Modugno">Francesmary Modugno</name><affiliation><nlm:aff id="A78">Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA, 77030</nlm:aff></affiliation><affiliation><nlm:aff id="A80">Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA, 77030</nlm:aff></affiliation><affiliation><nlm:aff id="A86">Women's Cancer Research Program, Magee-Womens Research Institute and University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA, 15213</nlm:aff></affiliation></author><author><name sortKey="Moysich, Kirsten B" sort="Moysich, Kirsten B" uniqKey="Moysich K" first="Kirsten B." last="Moysich">Kirsten B. Moysich</name><affiliation><nlm:aff id="A87">Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, NY, USA, 14263</nlm:aff></affiliation></author><author><name sortKey="Nakanishi, Toru" sort="Nakanishi, Toru" uniqKey="Nakanishi T" first="Toru" last="Nakanishi">Toru Nakanishi</name><affiliation><nlm:aff id="A88">Department of Gynecologic Oncology, Aichi Cancer Center Central Hospital, Nagoya, Aichi, Nagoya, 464-8681, Japan</nlm:aff></affiliation></author><author><name sortKey="Narod, Steven A" sort="Narod, Steven A" uniqKey="Narod S" first="Steven A." last="Narod">Steven A. Narod</name><affiliation><nlm:aff id="A89">Women's College Research Institute, University of Toronto, Toronto, Ontario, Canada, M5G 1N8</nlm:aff></affiliation></author><author><name sortKey="Nedergaard, Lotte" sort="Nedergaard, Lotte" uniqKey="Nedergaard L" first="Lotte" last="Nedergaard">Lotte Nedergaard</name><affiliation><nlm:aff id="A90">Department of Pathology, Rigshospitalet, University of Copenhagen, 2100, Denmark</nlm:aff></affiliation></author><author><name sortKey="Ness, Roberta B" sort="Ness, Roberta B" uniqKey="Ness R" first="Roberta B." last="Ness">Roberta B. Ness</name><affiliation><nlm:aff id="A91">The University of Texas School of Public Health, Houston, TX, USA, 77030</nlm:aff></affiliation></author><author><name sortKey="Nevanlinna, Heli" sort="Nevanlinna, Heli" uniqKey="Nevanlinna H" first="Heli" last="Nevanlinna">Heli Nevanlinna</name><affiliation><nlm:aff id="A26">Department of Obstetrics and Gynecology, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland, 00530</nlm:aff></affiliation></author><author><name sortKey="Nickels, Stefan" sort="Nickels, Stefan" uniqKey="Nickels S" first="Stefan" last="Nickels">Stefan Nickels</name><affiliation><nlm:aff id="A29">German Cancer Research Center, Division of Cancer Epidemiology, 69120, Heidelberg, Germany</nlm:aff></affiliation></author><author><name sortKey="Noushmehr, Houtan" sort="Noushmehr, Houtan" uniqKey="Noushmehr H" first="Houtan" last="Noushmehr">Houtan Noushmehr</name><affiliation><nlm:aff id="A32">Department of Urology, Microbiology and Preventive Medicine, University of Southern California, Norris Comprehensive Cancer Center, Los Angeles, CA, USA, 90089</nlm:aff></affiliation><affiliation><nlm:aff id="A92">USC Epigenome Center, Keck School of Medicine, University of Southern California, Norris Comprehensive Cancer Center, Los Angeles, CA, 90089</nlm:aff></affiliation></author><author><name sortKey="Odunsi, Kunle" sort="Odunsi, Kunle" uniqKey="Odunsi K" first="Kunle" last="Odunsi">Kunle Odunsi</name><affiliation><nlm:aff id="A93">Department of Gynecologic Oncology, Roswell Park Cancer Institute, Buffalo, NY, USA, 14263</nlm:aff></affiliation></author><author><name sortKey="Olson, Sara H" sort="Olson, Sara H" uniqKey="Olson S" first="Sara H." last="Olson">Sara H. Olson</name><affiliation><nlm:aff id="A94">Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY, USA, 10065</nlm:aff></affiliation></author><author><name sortKey="Orlow, Irene" sort="Orlow, Irene" uniqKey="Orlow I" first="Irene" last="Orlow">Irene Orlow</name><affiliation><nlm:aff id="A94">Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY, USA, 10065</nlm:aff></affiliation></author><author><name sortKey="Paul, James" sort="Paul, James" uniqKey="Paul J" first="James" last="Paul">James Paul</name><affiliation><nlm:aff id="A51">The Beatson West of Scotland Cancer Centre, Glasgow, G12 0YN, UK</nlm:aff></affiliation></author><author><name sortKey="Pearce, Celeste L" sort="Pearce, Celeste L" uniqKey="Pearce C" first="Celeste L" last="Pearce">Celeste L. Pearce</name><affiliation><nlm:aff id="A2">Department of Preventive Medicine, Keck School of Medicine, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA, USA, 90033</nlm:aff></affiliation></author><author><name sortKey="Pejovic, Tanja" sort="Pejovic, Tanja" uniqKey="Pejovic T" first="Tanja" last="Pejovic">Tanja Pejovic</name><affiliation><nlm:aff id="A95">Department of Obstetrics and Gynecology, Oregon Health and Science University, Portland, OR, USA, 97239</nlm:aff></affiliation><affiliation><nlm:aff id="A96">Knight Cancer Institute, Oregon Health and Science University, Portland, OR, USA, 97239</nlm:aff></affiliation></author><author><name sortKey="Pelttari, Liisa M" sort="Pelttari, Liisa M" uniqKey="Pelttari L" first="Liisa M." last="Pelttari">Liisa M. Pelttari</name><affiliation><nlm:aff id="A26">Department of Obstetrics and Gynecology, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland, 00530</nlm:aff></affiliation></author><author><name sortKey="Pike, Malcolm C" sort="Pike, Malcolm C" uniqKey="Pike M" first="Malcolm C." last="Pike">Malcolm C. Pike</name><affiliation><nlm:aff id="A2">Department of Preventive Medicine, Keck School of Medicine, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA, USA, 90033</nlm:aff></affiliation><affiliation><nlm:aff id="A94">Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY, USA, 10065</nlm:aff></affiliation></author><author><name sortKey="Poole, Elizabeth M" sort="Poole, Elizabeth M" uniqKey="Poole E" first="Elizabeth M." last="Poole">Elizabeth M. Poole</name><affiliation><nlm:aff id="A97">Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA, 02115</nlm:aff></affiliation><affiliation><nlm:aff id="A98">Channing Laboratory, Harvard Medical School and Brigham and Women's Hospital, Boston, MA, USA, 02115</nlm:aff></affiliation></author><author><name sortKey="Raska, Paola" sort="Raska, Paola" uniqKey="Raska P" first="Paola" last="Raska">Paola Raska</name><affiliation><nlm:aff id="A18">Case Comprehensive Cancer Center, Case Western Reserve University School of Medicine, Cleveland, OH, USA, 44195</nlm:aff></affiliation></author><author><name sortKey="Renner, Stefan P" sort="Renner, Stefan P" uniqKey="Renner S" first="Stefan P." last="Renner">Stefan P. Renner</name><affiliation><nlm:aff id="A19">University Hospital Erlangen, Department of Gynecology and Obstetrics, Friedrich-Alexander-University Erlangen-Nuremberg, Comprehensive Cancer Center, Erlangen, 91054, Germany</nlm:aff></affiliation></author><author><name sortKey="Risch, Harvey A" sort="Risch, Harvey A" uniqKey="Risch H" first="Harvey A." last="Risch">Harvey A. Risch</name><affiliation><nlm:aff id="A99">Department of Epidemiology and Public Health, Yale University School of Public Health and School of Medicine, New Haven, CT, USA, 06520</nlm:aff></affiliation></author><author><name sortKey="Rodriguez Rodriguez, Lorna" sort="Rodriguez Rodriguez, Lorna" uniqKey="Rodriguez Rodriguez L" first="Lorna" last="Rodriguez-Rodriguez">Lorna Rodriguez-Rodriguez</name><affiliation><nlm:aff id="A17">The Cancer Institute of New Jersey, Robert Wood Johnson Medical School, New Brunswick, NJ, USA, 08901</nlm:aff></affiliation></author><author><name sortKey="Rossing, Mary Anne" sort="Rossing, Mary Anne" uniqKey="Rossing M" first="Mary Anne" last="Rossing">Mary Anne Rossing</name><affiliation><nlm:aff id="A100">Program in Epidemiology, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA, 98109</nlm:aff></affiliation><affiliation><nlm:aff id="A101">Department of Epidemiology, University of Washington, Seattle, WA, USA, 98109</nlm:aff></affiliation></author><author><name sortKey="Rudolph, Anja" sort="Rudolph, Anja" uniqKey="Rudolph A" first="Anja" last="Rudolph">Anja Rudolph</name><affiliation><nlm:aff id="A29">German Cancer Research Center, Division of Cancer Epidemiology, 69120, Heidelberg, Germany</nlm:aff></affiliation></author><author><name sortKey="Runnebaum, Ingo B" sort="Runnebaum, Ingo B" uniqKey="Runnebaum I" first="Ingo B." last="Runnebaum">Ingo B. Runnebaum</name><affiliation><nlm:aff id="A42">Department of Gynecology and Obstetrics, Jena University Hospital, 07743, Jena, Germany</nlm:aff></affiliation></author><author><name sortKey="Rzepecka, Iwona K" sort="Rzepecka, Iwona K" uniqKey="Rzepecka I" first="Iwona K." last="Rzepecka">Iwona K. Rzepecka</name><affiliation><nlm:aff id="A37">Department of Molecular Pathology, The Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland, 02-781</nlm:aff></affiliation></author><author><name sortKey="Salvesen, Helga B" sort="Salvesen, Helga B" uniqKey="Salvesen H" first="Helga B." last="Salvesen">Helga B. Salvesen</name><affiliation><nlm:aff id="A57">Department of Gynecology and Obstetrics, Haukeland University Hospital, Bergen, HB 5006, Norway</nlm:aff></affiliation><affiliation><nlm:aff id="A58">Department of Clinical Medicine, University of Bergen, 5006, Bergen, Norway</nlm:aff></affiliation></author><author><name sortKey="Schwaab, Ira" sort="Schwaab, Ira" uniqKey="Schwaab I" first="Ira" last="Schwaab">Ira Schwaab</name><affiliation><nlm:aff id="A102">Institut für Humangenetik Wiesbaden, 65187, Wiesbaden, Germany</nlm:aff></affiliation></author><author><name sortKey="Severi, Gianluca" sort="Severi, Gianluca" uniqKey="Severi G" first="Gianluca" last="Severi">Gianluca Severi</name><affiliation><nlm:aff id="A15">Cancer Epidemiology Centre, The Cancer Council Victoria, Melbourne, Carlton VIC 3053, Australia</nlm:aff></affiliation><affiliation><nlm:aff id="A16">Centre for Molecular, Environmental, Genetic and Analytical Epidemiology, University of Melbourne, Melbourne, VIC 3010, Australia</nlm:aff></affiliation></author><author><name sortKey="Shridhar, Vijayalakshmi" sort="Shridhar, Vijayalakshmi" uniqKey="Shridhar V" first="Vijayalakshmi" last="Shridhar">Vijayalakshmi Shridhar</name><affiliation><nlm:aff id="A103">Department of Laboratory Medicine and Pathology, Division of Anatomic Pathology, Mayo Clinic, Rochester, MN, USA, 55905</nlm:aff></affiliation></author><author><name sortKey="Shu, Xiao Ou" sort="Shu, Xiao Ou" uniqKey="Shu X" first="Xiao-Ou" last="Shu">Xiao-Ou Shu</name><affiliation><nlm:aff id="A27">Vanderbilt Epidemiology Center and Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN, USA, 37232</nlm:aff></affiliation></author><author><name sortKey="Shvetsov, Yurii B" sort="Shvetsov, Yurii B" uniqKey="Shvetsov Y" first="Yurii B." last="Shvetsov">Yurii B. Shvetsov</name><affiliation><nlm:aff id="A81">Cancer Epidemiology Program, University of Hawaii Cancer Center, Hawaii, USA, 96813</nlm:aff></affiliation></author><author><name sortKey="Sieh, Weiva" sort="Sieh, Weiva" uniqKey="Sieh W" first="Weiva" last="Sieh">Weiva Sieh</name><affiliation><nlm:aff id="A83">Department of Health Research and Policy - Epidemiology, Stanford University School of Medicine, Stanford CA, USA, 94305</nlm:aff></affiliation></author><author><name sortKey="Song, Honglin" sort="Song, Honglin" uniqKey="Song H" first="Honglin" last="Song">Honglin Song</name><affiliation><nlm:aff id="A3">Department of Oncology, University of Cambridge, Cambridge, CB1 8RN, UK</nlm:aff></affiliation></author><author><name sortKey="Southey, Melissa C" sort="Southey, Melissa C" uniqKey="Southey M" first="Melissa C." last="Southey">Melissa C. Southey</name><affiliation><nlm:aff id="A104">Genetic Epidemiology Laboratory, Department of Pathology, The University of Melbourne, Melbourne, VIC 3053, Australia</nlm:aff></affiliation></author><author><name sortKey="Spiewankiewicz, Beata" sort="Spiewankiewicz, Beata" uniqKey="Spiewankiewicz B" first="Beata" last="Spiewankiewicz">Beata Spiewankiewicz</name><affiliation><nlm:aff id="A105">Department of Gynecologic Oncology, The Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland, 02-781</nlm:aff></affiliation></author><author><name sortKey="Stram, Daniel" sort="Stram, Daniel" uniqKey="Stram D" first="Daniel" last="Stram">Daniel Stram</name><affiliation><nlm:aff id="A2">Department of Preventive Medicine, Keck School of Medicine, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA, USA, 90033</nlm:aff></affiliation></author><author><name sortKey="Sutphen, Rebecca" sort="Sutphen, Rebecca" uniqKey="Sutphen R" first="Rebecca" last="Sutphen">Rebecca Sutphen</name><affiliation><nlm:aff id="A106">Pediatrics Epidemiology Center, College of Medicine, University of South Florida, Tampa, FL, USA, 33612</nlm:aff></affiliation></author><author><name sortKey="Teo, Soo Hwang" sort="Teo, Soo Hwang" uniqKey="Teo S" first="Soo-Hwang" last="Teo">Soo-Hwang Teo</name><affiliation><nlm:aff id="A77">Department of Obstetrics and Gynaecology, University Malaya Medical Centre, University Malaya, 59100 Kuala Lumpur, Federal Territory of Kuala Lumpur, Malaysia</nlm:aff></affiliation></author><author><name sortKey="Terry, Kathryn L" sort="Terry, Kathryn L" uniqKey="Terry K" first="Kathryn L." last="Terry">Kathryn L. Terry</name><affiliation><nlm:aff id="A36">Obstetrics and Gynecology Epidemiology Center, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA, 02115</nlm:aff></affiliation></author><author><name sortKey="Tessier, Daniel C" sort="Tessier, Daniel C" uniqKey="Tessier D" first="Daniel C." last="Tessier">Daniel C. Tessier</name><affiliation><nlm:aff id="A14">McGill University and Génome Québec Innovation Centre, Montréal (Québec) Canada, H3A 0G1</nlm:aff></affiliation></author><author><name sortKey="Thompson, Pamela J" sort="Thompson, Pamela J" uniqKey="Thompson P" first="Pamela J." last="Thompson">Pamela J. Thompson</name><affiliation><nlm:aff id="A53">Samuel Oschin Comprehensive Cancer Center Institute, Cedars Sinai Medical Center, Los Angeles, CA, USA, 90048</nlm:aff></affiliation></author><author><name sortKey="Tworoger, Shelley S" sort="Tworoger, Shelley S" uniqKey="Tworoger S" first="Shelley S." last="Tworoger">Shelley S. Tworoger</name><affiliation><nlm:aff id="A97">Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA, 02115</nlm:aff></affiliation><affiliation><nlm:aff id="A98">Channing Laboratory, Harvard Medical School and Brigham and Women's Hospital, Boston, MA, USA, 02115</nlm:aff></affiliation></author><author><name sortKey="Van Altena, Anne M" sort="Van Altena, Anne M" uniqKey="Van Altena A" first="Anne M." last="Van Altena">Anne M. Van Altena</name><affiliation><nlm:aff id="A82">Department of Gynaecology, Radboud University Medical Centre, Nijmegen, HB 6500, Netherlands</nlm:aff></affiliation></author><author><name sortKey="Vergote, Ignace" sort="Vergote, Ignace" uniqKey="Vergote I" first="Ignace" last="Vergote">Ignace Vergote</name><affiliation><nlm:aff id="A38">Division of Gynecologic Oncology, Department of Obstetrics and Gynaecology and Leuven Cancer Institute, University Hospitals Leuven, Leuven, Belgium, 3000</nlm:aff></affiliation></author><author><name sortKey="Vierkant, Robert A" sort="Vierkant, Robert A" uniqKey="Vierkant R" first="Robert A." last="Vierkant">Robert A. Vierkant</name><affiliation><nlm:aff id="A31">Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, MN, USA, 55905</nlm:aff></affiliation></author><author><name sortKey="Vincent, Daniel" sort="Vincent, Daniel" uniqKey="Vincent D" first="Daniel" last="Vincent">Daniel Vincent</name><affiliation><nlm:aff id="A14">McGill University and Génome Québec Innovation Centre, Montréal (Québec) Canada, H3A 0G1</nlm:aff></affiliation></author><author><name sortKey="Vitonis, Allison F" sort="Vitonis, Allison F" uniqKey="Vitonis A" first="Allison F." last="Vitonis">Allison F. Vitonis</name><affiliation><nlm:aff id="A36">Obstetrics and Gynecology Epidemiology Center, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA, 02115</nlm:aff></affiliation></author><author><name sortKey="Wang Gohrke, Shan" sort="Wang Gohrke, Shan" uniqKey="Wang Gohrke S" first="Shan" last="Wang-Gohrke">Shan Wang-Gohrke</name><affiliation><nlm:aff id="A107">Department of Obstetrics and Gynecology, University of Ulm, Ulm, 89081, Germany</nlm:aff></affiliation></author><author><name sortKey="Weber, Rachel Palmieri" sort="Weber, Rachel Palmieri" uniqKey="Weber R" first="Rachel Palmieri" last="Weber">Rachel Palmieri Weber</name><affiliation><nlm:aff id="A108">Department of Community and Family Medicine, Duke University Medical Center, Durham, NC, USA, 27708</nlm:aff></affiliation></author><author><name sortKey="Wentzensen, Nicolas" sort="Wentzensen, Nicolas" uniqKey="Wentzensen N" first="Nicolas" last="Wentzensen">Nicolas Wentzensen</name><affiliation><nlm:aff id="A22">Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda MD, USA, 20892</nlm:aff></affiliation></author><author><name sortKey="Whittemore, Alice S" sort="Whittemore, Alice S" uniqKey="Whittemore A" first="Alice S." last="Whittemore">Alice S. Whittemore</name><affiliation><nlm:aff id="A83">Department of Health Research and Policy - Epidemiology, Stanford University School of Medicine, Stanford CA, USA, 94305</nlm:aff></affiliation></author><author><name sortKey="Wik, Elisabeth" sort="Wik, Elisabeth" uniqKey="Wik E" first="Elisabeth" last="Wik">Elisabeth Wik</name><affiliation><nlm:aff id="A57">Department of Gynecology and Obstetrics, Haukeland University Hospital, Bergen, HB 5006, Norway</nlm:aff></affiliation><affiliation><nlm:aff id="A58">Department of Clinical Medicine, University of Bergen, 5006, Bergen, Norway</nlm:aff></affiliation></author><author><name sortKey="Wilkens, Lynne R" sort="Wilkens, Lynne R" uniqKey="Wilkens L" first="Lynne R." last="Wilkens">Lynne R. Wilkens</name><affiliation><nlm:aff id="A81">Cancer Epidemiology Program, University of Hawaii Cancer Center, Hawaii, USA, 96813</nlm:aff></affiliation></author><author><name sortKey="Winterhoff, Boris" sort="Winterhoff, Boris" uniqKey="Winterhoff B" first="Boris" last="Winterhoff">Boris Winterhoff</name><affiliation><nlm:aff id="A109">Department of Obstetrics and Gynecology, Mayo Clinic, Rochester, MN, USA, 55905</nlm:aff></affiliation></author><author><name sortKey="Woo, Yin Ling" sort="Woo, Yin Ling" uniqKey="Woo Y" first="Yin Ling" last="Woo">Yin Ling Woo</name><affiliation><nlm:aff id="A77">Department of Obstetrics and Gynaecology, University Malaya Medical Centre, University Malaya, 59100 Kuala Lumpur, Federal Territory of Kuala Lumpur, Malaysia</nlm:aff></affiliation></author><author><name sortKey="Wu, Anna H" sort="Wu, Anna H" uniqKey="Wu A" first="Anna H." last="Wu">Anna H. Wu</name><affiliation><nlm:aff id="A2">Department of Preventive Medicine, Keck School of Medicine, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA, USA, 90033</nlm:aff></affiliation></author><author><name sortKey="Xiang, Yong Bing" sort="Xiang, Yong Bing" uniqKey="Xiang Y" first="Yong-Bing" last="Xiang">Yong-Bing Xiang</name><affiliation><nlm:aff id="A110">Shanghai Cancer Institute, Shanghai, China, 2200-25</nlm:aff></affiliation></author><author><name sortKey="Yang, Hannah P" sort="Yang, Hannah P" uniqKey="Yang H" first="Hannah P." last="Yang">Hannah P. Yang</name><affiliation><nlm:aff id="A22">Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda MD, USA, 20892</nlm:aff></affiliation></author><author><name sortKey="Zheng, Wei" sort="Zheng, Wei" uniqKey="Zheng W" first="Wei" last="Zheng">Wei Zheng</name><affiliation><nlm:aff id="A27">Vanderbilt Epidemiology Center and Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN, USA, 37232</nlm:aff></affiliation></author><author><name sortKey="Ziogas, Argyrios" sort="Ziogas, Argyrios" uniqKey="Ziogas A" first="Argyrios" last="Ziogas">Argyrios Ziogas</name><affiliation><nlm:aff id="A111">Department of Epidemiology, Center for Cancer Genetics Research and Prevention, School of Medicine, University of California Irvine, Irvine, California, USA, 92697</nlm:aff></affiliation></author><author><name sortKey="Zulkifli, Famida" sort="Zulkifli, Famida" uniqKey="Zulkifli F" first="Famida" last="Zulkifli">Famida Zulkifli</name><affiliation><nlm:aff id="A77">Department of Obstetrics and Gynaecology, University Malaya Medical Centre, University Malaya, 59100 Kuala Lumpur, Federal Territory of Kuala Lumpur, Malaysia</nlm:aff></affiliation></author><author><name sortKey="Phelan, Catherine M" sort="Phelan, Catherine M" uniqKey="Phelan C" first="Catherine M." last="Phelan">Catherine M. Phelan</name><affiliation><nlm:aff id="A1">Department of Cancer Epidemiology, Division of Population Sciences, Moffitt Cancer Center, Tampa, FL, USA, 33612</nlm:aff></affiliation></author><author><name sortKey="Iversen, Edwin" sort="Iversen, Edwin" uniqKey="Iversen E" first="Edwin" last="Iversen">Edwin Iversen</name><affiliation><nlm:aff id="A112">Department of Statistical Science, Duke University, Durham, NC, USA, 27708</nlm:aff></affiliation></author><author><name sortKey="Schildkraut, Joellen M" sort="Schildkraut, Joellen M" uniqKey="Schildkraut J" first="Joellen M." last="Schildkraut">Joellen M. Schildkraut</name><affiliation><nlm:aff id="A108">Department of Community and Family Medicine, Duke University Medical Center, Durham, NC, USA, 27708</nlm:aff></affiliation><affiliation><nlm:aff id="A113">Cancer Prevention, Detection and Control Research Program, Duke Cancer Institute, Durham, North Carolina, USA, 27708-0251</nlm:aff></affiliation></author><author><name sortKey="Berchuck, Andrew" sort="Berchuck, Andrew" uniqKey="Berchuck A" first="Andrew" last="Berchuck">Andrew Berchuck</name><affiliation><nlm:aff id="A114">Department of Obstetrics and Gynecology, Duke Comprehensive Cancer Center, Durham, NC, USA, 27708</nlm:aff></affiliation></author><author><name sortKey="Fridley, Brooke L" sort="Fridley, Brooke L" uniqKey="Fridley B" first="Brooke L." last="Fridley">Brooke L. Fridley</name><affiliation><nlm:aff id="A115">Department of Biostatistics, University of Kansas Medical Center, Kansas City, KS, USA, 66160</nlm:aff></affiliation></author><author><name sortKey="Goode, Ellen L" sort="Goode, Ellen L" uniqKey="Goode E" first="Ellen L." last="Goode">Ellen L. Goode</name><affiliation><nlm:aff id="A31">Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, MN, USA, 55905</nlm:aff></affiliation></author><author><name sortKey="Pharoah, Paul D P" sort="Pharoah, Paul D P" uniqKey="Pharoah P" first="Paul D. P." last="Pharoah">Paul D. P. Pharoah</name><affiliation><nlm:aff id="A11">Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, CB1 8RN, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A43">Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, CB1 8RN, UK</nlm:aff></affiliation></author><author><name sortKey="Monteiro, Alvaro N A" sort="Monteiro, Alvaro N A" uniqKey="Monteiro A" first="Alvaro N. A." last="Monteiro">Alvaro N. A. Monteiro</name><affiliation><nlm:aff id="A1">Department of Cancer Epidemiology, Division of Population Sciences, Moffitt Cancer Center, Tampa, FL, USA, 33612</nlm:aff></affiliation></author><author><name sortKey="Sellers, Thomas A" sort="Sellers, Thomas A" uniqKey="Sellers T" first="Thomas A." last="Sellers">Thomas A. Sellers</name><affiliation><nlm:aff id="A1">Department of Cancer Epidemiology, Division of Population Sciences, Moffitt Cancer Center, Tampa, FL, USA, 33612</nlm:aff></affiliation></author><author><name sortKey="Gayther, Simon A" sort="Gayther, Simon A" uniqKey="Gayther S" first="Simon A." last="Gayther">Simon A. Gayther</name><affiliation><nlm:aff id="A2">Department of Preventive Medicine, Keck School of Medicine, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA, USA, 90033</nlm:aff></affiliation></author></analytic><series><title level="j">Nature communications</title><idno type="eISSN">2041-1723</idno><imprint><date when="2013">2013</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p id="P1">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 binding site 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 (OR=1.12, <italic>P</italic>=10<sup>−8</sup>) mapping to an inversion polymorphism at 17q21.31. Additional genotyping of non-miRSNPs at 17q21.31 reveals stronger signals outside the inversion (<italic>P</italic>=10<sup>−10</sup>). Variation at 17q21.31 associates with neurological diseases, and our collaboration is the first to report an association with EOC susceptibility. 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<front><journal-meta><journal-id journal-id-type="nlm-journal-id">101528555</journal-id><journal-id journal-id-type="pubmed-jr-id">37539</journal-id><journal-id journal-id-type="nlm-ta">Nat Commun</journal-id><journal-id journal-id-type="iso-abbrev">Nat Commun</journal-id><journal-title-group><journal-title>Nature communications</journal-title></journal-title-group><issn pub-type="epub">2041-1723</issn></journal-meta><article-meta><article-id pub-id-type="pmid">23535648</article-id><article-id pub-id-type="pmc">3709460</article-id><article-id pub-id-type="doi">10.1038/ncomms2613</article-id><article-id pub-id-type="manuscript">NIHMS447293</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>Identification and molecular characterization of a new ovarian cancer susceptibility locus at 17q21.31</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Permuth-Wey</surname><given-names>Jennifer</given-names></name><xref ref-type="aff" rid="A1">1</xref><xref rid="FN2" ref-type="author-notes">*</xref></contrib><contrib contrib-type="author"><name><surname>Lawrenson</surname><given-names>Kate</given-names></name><xref ref-type="aff" rid="A2">2</xref><xref rid="FN2" ref-type="author-notes">*</xref></contrib><contrib contrib-type="author"><name><surname>Shen</surname><given-names>Howard C.</given-names></name><xref ref-type="aff" rid="A2">2</xref><xref rid="FN2" ref-type="author-notes">*</xref></contrib><contrib contrib-type="author"><name><surname>Velkova</surname><given-names>Aneliya</given-names></name><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Tyrer</surname><given-names>Jonathan P.</given-names></name><xref ref-type="aff" rid="A3">3</xref></contrib><contrib contrib-type="author"><name><surname>Chen</surname><given-names>Zhihua</given-names></name><xref ref-type="aff" rid="A4">4</xref></contrib><contrib contrib-type="author"><name><surname>Lin</surname><given-names>Hui-Yi</given-names></name><xref ref-type="aff" rid="A5">5</xref></contrib><contrib contrib-type="author"><name><surname>Chen</surname><given-names>Y. Ann</given-names></name><xref ref-type="aff" rid="A5">5</xref></contrib><contrib contrib-type="author"><name><surname>Tsai</surname><given-names>Ya-Yu</given-names></name><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Qu</surname><given-names>Xiaotao</given-names></name><xref ref-type="aff" rid="A4">4</xref></contrib><contrib contrib-type="author"><name><surname>Ramus</surname><given-names>Susan J.</given-names></name><xref ref-type="aff" rid="A2">2</xref></contrib><contrib contrib-type="author"><name><surname>Karevan</surname><given-names>Rod</given-names></name><xref ref-type="aff" rid="A2">2</xref></contrib><contrib contrib-type="author"><name><surname>Lee</surname><given-names>Janet</given-names></name><xref ref-type="aff" rid="A2">2</xref></contrib><contrib contrib-type="author"><name><surname>Lee</surname><given-names>Nathan</given-names></name><xref ref-type="aff" rid="A2">2</xref></contrib><contrib contrib-type="author"><name><surname>Larson</surname><given-names>Melissa C.</given-names></name><xref ref-type="aff" rid="A6">6</xref></contrib><contrib contrib-type="author"><name><surname>Aben</surname><given-names>Katja K.</given-names></name><xref ref-type="aff" rid="A7">7</xref><xref ref-type="aff" rid="A8">8</xref></contrib><contrib contrib-type="author"><name><surname>Anton-Culver</surname><given-names>Hoda</given-names></name><xref ref-type="aff" rid="A9">9</xref></contrib><contrib contrib-type="author"><name><surname>Antonenkova</surname><given-names>Natalia</given-names></name><xref ref-type="aff" rid="A10">10</xref></contrib><contrib contrib-type="author"><name><surname>Antoniou</surname><given-names>Antonis</given-names></name><xref ref-type="aff" rid="A11">11</xref></contrib><contrib contrib-type="author"><name><surname>Armasu</surname><given-names>Sebastian M.</given-names></name><xref ref-type="aff" rid="A6">6</xref></contrib><contrib contrib-type="author"><collab>Australian Cancer Study</collab><xref ref-type="aff" rid="A12">12</xref></contrib><contrib contrib-type="author"><collab>Australian Ovarian Cancer Study</collab><xref ref-type="aff" rid="A12">12</xref><xref ref-type="aff" rid="A13">13</xref></contrib><contrib contrib-type="author"><name><surname>Bacot</surname><given-names>François</given-names></name><xref ref-type="aff" rid="A14">14</xref></contrib><contrib contrib-type="author"><name><surname>Baglietto</surname><given-names>Laura</given-names></name><xref ref-type="aff" rid="A15">15</xref><xref ref-type="aff" rid="A16">16</xref></contrib><contrib contrib-type="author"><name><surname>Bandera</surname><given-names>Elisa V.</given-names></name><xref ref-type="aff" rid="A17">17</xref></contrib><contrib contrib-type="author"><name><surname>Barnholtz-Sloan</surname><given-names>Jill</given-names></name><xref ref-type="aff" rid="A18">18</xref></contrib><contrib 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ref-type="aff" rid="A107">107</xref></contrib><contrib contrib-type="author"><name><surname>Weber</surname><given-names>Rachel Palmieri</given-names></name><xref ref-type="aff" rid="A108">108</xref></contrib><contrib contrib-type="author"><name><surname>Wentzensen</surname><given-names>Nicolas</given-names></name><xref ref-type="aff" rid="A22">22</xref></contrib><contrib contrib-type="author"><name><surname>Whittemore</surname><given-names>Alice S.</given-names></name><xref ref-type="aff" rid="A83">83</xref></contrib><contrib contrib-type="author"><name><surname>Wik</surname><given-names>Elisabeth</given-names></name><xref ref-type="aff" rid="A57">57</xref><xref ref-type="aff" rid="A58">58</xref></contrib><contrib contrib-type="author"><name><surname>Wilkens</surname><given-names>Lynne R.</given-names></name><xref ref-type="aff" rid="A81">81</xref></contrib><contrib contrib-type="author"><name><surname>Winterhoff</surname><given-names>Boris</given-names></name><xref ref-type="aff" rid="A109">109</xref></contrib><contrib contrib-type="author"><name><surname>Woo</surname><given-names>Yin Ling</given-names></name><xref ref-type="aff" rid="A77">77</xref></contrib><contrib contrib-type="author"><name><surname>Wu</surname><given-names>Anna H.</given-names></name><xref ref-type="aff" rid="A2">2</xref></contrib><contrib contrib-type="author"><name><surname>Xiang</surname><given-names>Yong-Bing</given-names></name><xref ref-type="aff" rid="A110">110</xref></contrib><contrib contrib-type="author"><name><surname>Yang</surname><given-names>Hannah P.</given-names></name><xref ref-type="aff" rid="A22">22</xref></contrib><contrib contrib-type="author"><name><surname>Zheng</surname><given-names>Wei</given-names></name><xref ref-type="aff" rid="A27">27</xref></contrib><contrib contrib-type="author"><name><surname>Ziogas</surname><given-names>Argyrios</given-names></name><xref ref-type="aff" rid="A111">111</xref></contrib><contrib contrib-type="author"><name><surname>Zulkifli</surname><given-names>Famida</given-names></name><xref ref-type="aff" rid="A77">77</xref></contrib><contrib contrib-type="author"><name><surname>Phelan</surname><given-names>Catherine M.</given-names></name><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Iversen</surname><given-names>Edwin</given-names></name><xref ref-type="aff" rid="A112">112</xref></contrib><contrib contrib-type="author"><name><surname>Schildkraut</surname><given-names>Joellen M.</given-names></name><xref ref-type="aff" rid="A108">108</xref><xref ref-type="aff" rid="A113">113</xref></contrib><contrib contrib-type="author"><name><surname>Berchuck</surname><given-names>Andrew</given-names></name><xref ref-type="aff" rid="A114">114</xref></contrib><contrib contrib-type="author"><name><surname>Fridley</surname><given-names>Brooke L.</given-names></name><xref ref-type="aff" rid="A115">115</xref></contrib><contrib contrib-type="author"><name><surname>Goode</surname><given-names>Ellen L.</given-names></name><xref ref-type="aff" rid="A31">31</xref></contrib><contrib contrib-type="author"><name><surname>Pharoah</surname><given-names>Paul D. P.</given-names></name><xref ref-type="aff" rid="A11">11</xref><xref ref-type="aff" rid="A43">43</xref></contrib><contrib contrib-type="author"><name><surname>Monteiro</surname><given-names>Alvaro N.A.</given-names></name><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Sellers</surname><given-names>Thomas A.</given-names></name><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Gayther</surname><given-names>Simon A.</given-names></name><xref ref-type="aff" rid="A2">2</xref></contrib></contrib-group><aff id="A1"><label>1</label>Department of Cancer Epidemiology, Division of Population Sciences, Moffitt Cancer Center, Tampa, FL, USA, 33612</aff><aff id="A2"><label>2</label>Department of Preventive Medicine, Keck School of Medicine, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA, USA, 90033</aff><aff id="A3"><label>3</label>Department of Oncology, University of Cambridge, Cambridge, CB1 8RN, UK</aff><aff id="A4"><label>4</label>Department of Biomedical Informatics, Moffitt Cancer Center, Tampa, FL, USA, 33612</aff><aff id="A5"><label>5</label>Department of Biostatistics, Moffitt Cancer Center, Tampa, FL, USA, 33612</aff><aff id="A6"><label>6</label>Department of Health Science Research, Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN, USA, 55905</aff><aff id="A7"><label>7</label>Department of Epidemiology, Biostatistics and HTA, Radboud University Medical Centre, Nijmegen, HB 6500, Netherlands</aff><aff id="A8"><label>8</label>Comprehensive Cancer Center, the Netherlands, Utrecht, Amsterdam, 1066CX, The Netherlands</aff><aff id="A9"><label>9</label>Department of Epidemiology, Director of Genetic Epidemiology Research Institute, UCI Center of Medicine, University of California Irvine, Irvine, CA, USA, 92697</aff><aff id="A10"><label>10</label>Byelorussian Institute for Oncology and Medical Radiology Aleksandrov N.N., 223040, Minsk, Belarus</aff><aff id="A11"><label>11</label>Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, CB1 8RN, UK</aff><aff id="A12"><label>12</label>Queensland Institute of Medical Research, Brisbane QLD 4006, Australia</aff><aff id="A13"><label>13</label>Cancer Genetics Laboratory, Research Division, Peter MacCallum Cancer Centre, Melbourne, VIC 3002, Australia</aff><aff id="A14"><label>14</label>McGill University and Génome Québec Innovation Centre, Montréal (Québec) Canada, H3A 0G1</aff><aff id="A15"><label>15</label>Cancer Epidemiology Centre, The Cancer Council Victoria, Melbourne, Carlton VIC 3053, Australia</aff><aff id="A16"><label>16</label>Centre for Molecular, Environmental, Genetic and Analytical Epidemiology, University of Melbourne, Melbourne, VIC 3010, Australia</aff><aff id="A17"><label>17</label>The Cancer Institute of New Jersey, Robert Wood Johnson Medical School, New Brunswick, NJ, USA, 08901</aff><aff id="A18"><label>18</label>Case Comprehensive Cancer Center, Case Western Reserve University School of Medicine, Cleveland, OH, USA, 44195</aff><aff id="A19"><label>19</label>University Hospital Erlangen, Department of Gynecology and Obstetrics, Friedrich-Alexander-University Erlangen-Nuremberg, Comprehensive Cancer Center, Erlangen, 91054, Germany</aff><aff id="A20"><label>20</label>Massachusetts General Hospital, Boston, MA, USA, 02114</aff><aff id="A21"><label>21</label>Gynaecology Research Unit, Hannover Medical School, Hannover, 30625, Germany</aff><aff id="A22"><label>22</label>Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda MD, USA, 20892</aff><aff id="A23"><label>23</label>Genome Sciences Centre, BC Cancer Agency, Vancouver, BC, Canada, V5Z 1L3</aff><aff id="A24"><label>24</label>Department of Surgery and Cancer, Imperial College London, London, SW7 2AZ, UK</aff><aff id="A25"><label>25</label>Department of Pathology, Helsinki University Central Hospital, Helsinki, Finland, 00530</aff><aff id="A26"><label>26</label>Department of Obstetrics and Gynecology, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland, 00530</aff><aff id="A27"><label>27</label>Vanderbilt Epidemiology Center and Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN, USA, 37232</aff><aff id="A28"><label>28</label>Department of Pathology, University of Melbourne, Parkville, VIC 3053, Australia</aff><aff id="A29"><label>29</label>German Cancer Research Center, Division of Cancer Epidemiology, 69120, Heidelberg, Germany</aff><aff id="A30"><label>30</label>Department of Interdisciplinary Oncology, Moffitt Cancer Center, Tampa, FL, USA, 33612</aff><aff id="A31"><label>31</label>Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, MN, USA, 55905</aff><aff id="A32"><label>32</label>Department of Urology, Microbiology and Preventive Medicine, University of Southern California, Norris Comprehensive Cancer Center, Los Angeles, CA, USA, 90089</aff><aff id="A33"><label>33</label>Cancer Research UK, Genetic Epidemiology Unit, Dept of Public Health & Primary Care, University of Cambridge, Strangeways Research Lab, Cambridge, CB1 8RN, UK</aff><aff id="A34"><label>34</label>Department of Laboratory of Medicine and Pathology, Mayo Clinic, Rochester, MN, USA, 55905</aff><aff id="A35"><label>35</label>Division Epidemiology and Biostatistics, University of New Mexico, Albuquerque, NM, USA, 87131</aff><aff id="A36"><label>36</label>Obstetrics and Gynecology Epidemiology Center, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA, 02115</aff><aff id="A37"><label>37</label>Department of Molecular Pathology, The Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland, 02-781</aff><aff id="A38"><label>38</label>Division of Gynecologic Oncology, Department of Obstetrics and Gynaecology and Leuven Cancer Institute, University Hospitals Leuven, Leuven, Belgium, 3000</aff><aff id="A39"><label>39</label>Section of Biostatistics and Epidemiology, The Geisel School of Medicine at Dartmouth, Lebanon, NH, USA, 03755</aff><aff id="A40"><label>40</label>Department of Gynecology and Gynecologic Oncology, Dr. Horst Schmidt Klinik Wiesbaden, 65199, Wiesbaden, Germany</aff><aff id="A41"><label>41</label>Department of Gynecology and Gynecologic Oncology, Kliniken Essen-Mitte, 45136, Essen, Germany</aff><aff id="A42"><label>42</label>Department of Gynecology and Obstetrics, Jena University Hospital, 07743, Jena, Germany</aff><aff id="A43"><label>43</label>Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, CB1 8RN, UK</aff><aff id="A44"><label>44</label>Faculty of Medicine, University of Southampton, University Hospital Southampton, SO17 1BJ, UK</aff><aff id="A45"><label>45</label>Maggee Women's Hospital, Pittsburg, PA, USA, 15213</aff><aff id="A46"><label>46</label>Institute of Human Genetics, Friedrich-Alexander-University Erlangen-Nuremberg, 91054, Erlangen, Germany</aff><aff id="A47"><label>47</label>Department of Medicine, Division of Hematology and Oncology, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, USA, 90095</aff><aff id="A48"><label>48</label>Sections of Epidemiology and Genetics at the Institute of Cancer Research and Breakthrough Breast Cancer Research Centre, London, UK, SW7 3RP</aff><aff id="A49"><label>49</label>Gynaecological Cancer Research Centre, UCL EGA Institute for Women's Health, London, NW1 2BU, United Kingdom</aff><aff id="A50"><label>50</label>Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, VIC 3806, Australia</aff><aff id="A51"><label>51</label>The Beatson West of Scotland Cancer Centre, Glasgow, G12 0YN, UK</aff><aff id="A52"><label>52</label>Department of Women's Oncology, Moffitt Cancer Center, Tampa, FL, USA, 33612</aff><aff id="A53"><label>53</label>Samuel Oschin Comprehensive Cancer Center Institute, Cedars Sinai Medical Center, Los Angeles, CA, USA, 90048</aff><aff id="A54"><label>54</label>Gynecological Oncology Unit, The Royal Marsden Hospital, London, SW3 6JJ, United Kingdom</aff><aff id="A55"><label>55</label>International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland, 70-115</aff><aff id="A56"><label>56</label>Department of Epidemiology and Biostatistics, Karolinska Istitutet, Stockholm, Sweden, 171-77</aff><aff id="A57"><label>57</label>Department of Gynecology and Obstetrics, Haukeland University Hospital, Bergen, HB 5006, Norway</aff><aff id="A58"><label>58</label>Department of Clinical Medicine, University of Bergen, 5006, Bergen, Norway</aff><aff id="A59"><label>59</label>Clinics of Obstetrics and Gynaecology, Hannover Medical School, 30625, Hannover, Germany</aff><aff id="A60"><label>60</label>Department of Biochemistry and Molecular Biology, Oregon Health and Science University, Portland, OR, USA, 97239</aff><aff id="A61"><label>61</label>The Juliane Marie Centre, Department of Obstetrics and Gynecology, Rigshospitalet, Copenhagen, 2100, Denmark</aff><aff id="A62"><label>62</label>Department of Pathology, Molecular Unit, Herlev Hospital, University of Copenhagen, Denmark, 2730</aff><aff id="A63"><label>63</label>Virus, Lifestyle and Genes, Danish Cancer Society Research Center, DK-2100, Copenhagen, Denmark</aff><aff id="A64"><label>64</label>Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya, Aichi, 464-8681, Japan</aff><aff id="A65"><label>65</label>Department of Health Outcomes and Behavior, Moffitt Cancer Center, Tampa, FL, USA, 33612</aff><aff id="A66"><label>66</label>Department of Medical Oncology, Mayo Clinic, Rochester, MN, USA, 55905</aff><aff id="A67"><label>67</label>Women's Cancer Program at the Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA, 90048</aff><aff id="A68"><label>68</label>Section of Medicine, Institute of Cancer Research, Sutton, SM2 5NG, UK</aff><aff id="A69"><label>69</label>Department of Popluation Health Research, Alberta Health Services-Cancer Care, Calgary, Alberta, Canada and Departments of Medical Genetics and Oncology, University of Calgary, Calgary, AB, Canada, T2N 2T9</aff><aff id="A70"><label>70</label>Department of Urology, Radboud University Medical Centre, Nijmegen, HB 6500, Netherlands</aff><aff id="A71"><label>71</label>Department of Obsterics and Gynecology, Nagoya University Graduate School of Medicine, Nagoya, Aichi, 466-8550, Japan</aff><aff id="A72"><label>72</label>Vesalius Research Center, VIB, 3000, Leuven, Belgium</aff><aff id="A73"><label>73</label>Laboratory for Translational Genetics, Department of Oncology, University of Leuven, 3000, Leuven, Belgium</aff><aff id="A74"><label>74</label>Cancer Control Research, BC Cancer Agency, Vancouver, BC, Canada, G12 0YN</aff><aff id="A75"><label>75</label>Gynecology Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY, USA, 10021</aff><aff id="A76"><label>76</label>College of Pharmacy and Health Sciences, Texas Southern University, Houston, Texas, USA, 77044</aff><aff id="A77"><label>77</label>Department of Obstetrics and Gynaecology, University Malaya Medical Centre, University Malaya, 59100 Kuala Lumpur, Federal Territory of Kuala Lumpur, Malaysia</aff><aff id="A78"><label>78</label>Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA, 77030</aff><aff id="A79"><label>79</label>Department of Cancer Epidemiology and Prevention, The Maria Sklodowska-Curie Memorial Cancer Center, 02-781, Warsaw, Poland</aff><aff id="A80"><label>80</label>Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA, 77030</aff><aff id="A81"><label>81</label>Cancer Epidemiology Program, University of Hawaii Cancer Center, Hawaii, USA, 96813</aff><aff id="A82"><label>82</label>Department of Gynaecology, Radboud University Medical Centre, Nijmegen, HB 6500, Netherlands</aff><aff id="A83"><label>83</label>Department of Health Research and Policy - Epidemiology, Stanford University School of Medicine, Stanford CA, USA, 94305</aff><aff id="A84"><label>84</label>Dalla Lana School of Public Health, Faculty of Medicine, University of Toronto, ON, M5T 3M7, Canada</aff><aff id="A85"><label>85</label>Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada, M5G 1X5</aff><aff id="A86"><label>86</label>Women's Cancer Research Program, Magee-Womens Research Institute and University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA, 15213</aff><aff id="A87"><label>87</label>Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, NY, USA, 14263</aff><aff id="A88"><label>88</label>Department of Gynecologic Oncology, Aichi Cancer Center Central Hospital, Nagoya, Aichi, Nagoya, 464-8681, Japan</aff><aff id="A89"><label>89</label>Women's College Research Institute, University of Toronto, Toronto, Ontario, Canada, M5G 1N8</aff><aff id="A90"><label>90</label>Department of Pathology, Rigshospitalet, University of Copenhagen, 2100, Denmark</aff><aff id="A91"><label>91</label>The University of Texas School of Public Health, Houston, TX, USA, 77030</aff><aff id="A92"><label>92</label>USC Epigenome Center, Keck School of Medicine, University of Southern California, Norris Comprehensive Cancer Center, Los Angeles, CA, 90089</aff><aff id="A93"><label>93</label>Department of Gynecologic Oncology, Roswell Park Cancer Institute, Buffalo, NY, USA, 14263</aff><aff id="A94"><label>94</label>Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY, USA, 10065</aff><aff id="A95"><label>95</label>Department of Obstetrics and Gynecology, Oregon Health and Science University, Portland, OR, USA, 97239</aff><aff id="A96"><label>96</label>Knight Cancer Institute, Oregon Health and Science University, Portland, OR, USA, 97239</aff><aff id="A97"><label>97</label>Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA, 02115</aff><aff id="A98"><label>98</label>Channing Laboratory, Harvard Medical School and Brigham and Women's Hospital, Boston, MA, USA, 02115</aff><aff id="A99"><label>99</label>Department of Epidemiology and Public Health, Yale University School of Public Health and School of Medicine, New Haven, CT, USA, 06520</aff><aff id="A100"><label>100</label>Program in Epidemiology, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA, 98109</aff><aff id="A101"><label>101</label>Department of Epidemiology, University of Washington, Seattle, WA, USA, 98109</aff><aff id="A102"><label>102</label>Institut für Humangenetik Wiesbaden, 65187, Wiesbaden, Germany</aff><aff id="A103"><label>103</label>Department of Laboratory Medicine and Pathology, Division of Anatomic Pathology, Mayo Clinic, Rochester, MN, USA, 55905</aff><aff id="A104"><label>104</label>Genetic Epidemiology Laboratory, Department of Pathology, The University of Melbourne, Melbourne, VIC 3053, Australia</aff><aff id="A105"><label>105</label>Department of Gynecologic Oncology, The Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland, 02-781</aff><aff id="A106"><label>106</label>Pediatrics Epidemiology Center, College of Medicine, University of South Florida, Tampa, FL, USA, 33612</aff><aff id="A107"><label>107</label>Department of Obstetrics and Gynecology, University of Ulm, Ulm, 89081, Germany</aff><aff id="A108"><label>108</label>Department of Community and Family Medicine, Duke University Medical Center, Durham, NC, USA, 27708</aff><aff id="A109"><label>109</label>Department of Obstetrics and Gynecology, Mayo Clinic, Rochester, MN, USA, 55905</aff><aff id="A110"><label>110</label>Shanghai Cancer Institute, Shanghai, China, 2200-25</aff><aff id="A111"><label>111</label>Department of Epidemiology, Center for Cancer Genetics Research and Prevention, School of Medicine, University of California Irvine, Irvine, California, USA, 92697</aff><aff id="A112"><label>112</label>Department of Statistical Science, Duke University, Durham, NC, USA, 27708</aff><aff id="A113"><label>113</label>Cancer Prevention, Detection and Control Research Program, Duke Cancer Institute, Durham, North Carolina, USA, 27708-0251</aff><aff id="A114"><label>114</label>Department of Obstetrics and Gynecology, Duke Comprehensive Cancer Center, Durham, NC, USA, 27708</aff><aff id="A115"><label>115</label>Department of Biostatistics, University of Kansas Medical Center, Kansas City, KS, USA, 66160</aff><author-notes><corresp id="FN1">Correspondence: Jennifer Permuth-Wey, PhD, Moffitt Cancer Center, 12902 Magnolia Dr., MRC-CANT, Tampa, Florida 33612, <email>Jenny.Wey@moffitt.org</email> Telephone: 813-745-5744, Fax: 813-745-6525; Thomas A. Sellers, PhD, Moffitt Cancer Center, 12902 Magnolia Dr, Tampa, Florida 33612, <email>Thomas.Sellers@moffitt.org</email>, Telephone: 813-745-1315, Fax: 813-449-8126; Simon Gayther, PhD, University of Southern California/Keck School of Medicine, Harlyne Norris Research Tower 1450 Biggy Street Los Angeles, CA 90033, <email>gayther@usc.edu</email>, Telephone: 323 442-8112, Fax: 323 442-7787</corresp><fn id="FN2" fn-type="equal"><label>*</label><p>contributed equally to this manuscript</p></fn></author-notes><pub-date pub-type="nihms-submitted"><day>21</day><month>6</month><year>2013</year></pub-date><pub-date pub-type="ppub"><year>2013</year></pub-date><pub-date pub-type="pmc-release"><day>12</day><month>7</month><year>2013</year></pub-date><volume>4</volume><fpage>1627</fpage><lpage>1627</lpage><pmc-comment>elocation-id from pubmed: 10.1038/ncomms2613</pmc-comment>
<permissions><license><license-p>Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: <ext-link ext-link-type="uri" xlink:href="http://www.nature.com/authors/editorial_policies/license.html#terms">http://www.nature.com/authors/editorial_policies/license.html#terms</ext-link></license-p></license></permissions><abstract><p id="P1">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 binding site 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 (OR=1.12, <italic>P</italic>=10<sup>−8</sup>) mapping to an inversion polymorphism at 17q21.31. Additional genotyping of non-miRSNPs at 17q21.31 reveals stronger signals outside the inversion (<italic>P</italic>=10<sup>−10</sup>). Variation at 17q21.31 associates 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 <italic>ARHGAP27</italic> and <italic>PLEKHM1</italic> as candidate EOC susceptibility genes.</p></abstract></article-meta></front><body><p id="P2">Genome wide association studies (GWAS) have identified hundreds of genetic variants conferring low penetrance susceptibility to cancer<sup><xref rid="R1" ref-type="bibr">1</xref></sup>. More than 90% of these variants lie in non protein-encoding sequences including non-coding RNAs and regions containing regulatory elements (i.e. enhancers, promoters, untranslated regions (UTRs))<sup><xref rid="R1" ref-type="bibr">1</xref></sup>. The emerging hypothesis is that common variants within non-coding regulatory regions influence expression of target genes, thereby conferring disease susceptibility<sup><xref rid="R1" ref-type="bibr">1</xref></sup>.</p><p id="P3">MicroRNAs (miRNAs) are short non-coding RNAs that regulate gene expression post-transcriptionally by binding primarily to the 3′ UTR of target messenger RNA (mRNA), causing translational inhibition and/or mRNA degradation<sup><xref rid="R2" ref-type="bibr">2</xref>-<xref rid="R4" ref-type="bibr">4</xref></sup>. MiRNAs have been shown to play a key role in the development of epithelial ovarian cancer (EOC) <sup><xref rid="R2" ref-type="bibr">2</xref></sup>. We <sup><xref rid="R5" ref-type="bibr">5</xref>,<xref rid="R6" ref-type="bibr">6</xref></sup> and others <sup><xref rid="R7" ref-type="bibr">7</xref></sup> have found evidence that various miRNA-related single nucleotide polymorphisms (miRSNPs) are associated with EOC risk, suggesting they may be key disruptors of gene function and contributors to disease susceptibility <sup><xref rid="R8" ref-type="bibr">8</xref>,<xref rid="R9" ref-type="bibr">9</xref></sup>. However, studies of miRSNPs that affect miRNA-mRNA binding have been restricted by small sample sizes and therefore have limited statistical power to identify associations at genome wide levels of significance<sup><xref rid="R7" ref-type="bibr">7</xref>-<xref rid="R9" ref-type="bibr">9</xref></sup>. Larger-scale studies and more systematic approaches are warranted to fully evaluate the role of miRSNPs and their contribution to disease susceptibility.</p><p id="P4">Here, we use the <italic>in silico</italic> algorithms, TargetScan <sup><xref rid="R10" ref-type="bibr">10</xref>,<xref rid="R11" ref-type="bibr">11</xref></sup> and Pictar <sup><xref rid="R12" ref-type="bibr">12</xref>,<xref rid="R13" ref-type="bibr">13</xref></sup> to predict miRNA:mRNA binding regions involving genes and miRNAs relevant to EOC, and align identified regions with SNPs in the dbSNP database (Methods). We then genotype 1,003 miRSNPs (or tagging SNPs with r<sup>2</sup>>0.80) in 18,174 EOC cases and 26,134 controls from 43 studies from the Ovarian Cancer Association Consortium (OCAC) (<xref rid="SD1" ref-type="supplementary-material">Supplementary Table S1</xref>). Genotyping was performed on a custom Illumina Infinium iSelect array designed as part of the Collaborative Oncological Gene-environment Study (COGS), an international effort that evaluated 211,155 SNPs and their association with ovarian, breast, and prostate cancer risk. Our investigation uncovers 17q21.31 as a new susceptibility locus for EOC, and we provide insights into candidate genes and possible functional mechanisms underlying disease development at this locus.</p><sec sec-type="results" id="S1"><title>Results</title><sec id="S2"><title>Association analyses</title><p id="P5">Seven hundred and sixty-seven of the 1,003 miRSNPs passed genotype quality control (QC) and were evaluated for association with invasive EOC risk; most of the miRSNPs that failed QC were monomorphic (see Methods). Primary analysis of 14,533 invasive EOC cases and 23,491 controls of European ancestry revealed four strongly correlated SNPs (r<sup>2</sup>=0.99; rs1052587, rs17574361, rs4640231, and rs916793) that mapped to 17q21.31 and were associated with increased risk (per allele odds ratio (OR) = 1.10, 95% CI 1.06-1.13) at a genome-wide level of significance (10<sup>−7</sup>); no other miRSNPs had associations stronger than P<10<sup>−4</sup> (<xref rid="SD1" ref-type="supplementary-material">Supplementary Fig. S1</xref>). The most significant association was for rs1052587 (<italic>P</italic>=1.9×10<sup>−7</sup>), and effects varied by histological subtype, with the strongest effect observed for invasive serous EOC cases (OR=1.12, <italic>P</italic>=4.6×10<sup>−8</sup>) (<xref rid="T1" ref-type="table">Table 1</xref>). No heterogeneity in ORs was observed across study sites (<xref rid="SD1" ref-type="supplementary-material">Supplementary Fig. S2</xref>).</p><p id="P6">Rs1052587, rs17574361, and rs4640231 reside in the 3′UTR of microtubule-associated protein tau (<italic>MAPT</italic>), KAT8 regulatory NSL complex subunit 1 (<italic>KANSL1/KIAA1267</italic>), and corticotrophin releasing hormone receptor 1 (<italic>CRHR1</italic>) genes, at putative binding sites for miR-34a, miR-130a, and miR-34c, respectively. The fourth SNP, rs916793, is perfectly correlated with rs4640231 and lies in a non-coding RNA, <italic>MAPT</italic>-antisense 1. 17q21.31 contains a ∼900kb inversion polymorphism<sup><xref rid="R14" ref-type="bibr">14</xref></sup> (ch 17: 43,624,578-44,525,051 MB, human genome build 37), and all three miRSNPs and the tagSNP are located within the inversion (<xref rid="F1" ref-type="fig">Fig. 1</xref>).</p><p id="P7">Chromosomes with the non-inverted or inverted segments of 17q21.31, respectively known as haplotype 1 (H1) and haplotype 2 (H2), represent two distinct lineages that diverged ∼3 million years ago and have not undergone any recombination event <sup><xref rid="R14" ref-type="bibr">14</xref></sup>. The four susceptibility alleles identified here reside on the H2 haplotype that is reported to be rare in Africans and East Asians, but is common (frequency >20%) and exhibits strong linkage disequilibrium (LD) among Europeans <sup><xref rid="R14" ref-type="bibr">14</xref></sup>, consistent with our findings. The H2 haplotype has a frequency of 22% among European women in our primary analysis (<xref rid="T1" ref-type="table">Table 1</xref>) but only 3.2% and 0.3% among Africans (151 invasive cases, 200 controls) and Asians (716 invasive cases, 1573 controls), respectively.</p><p id="P8">To increase genomic coverage at this locus, we evaluated an additional 142 non-miRSNPs at 17q21.31 that were also genotyped as part of COGS in the same series of OCAC cases and controls. We also imputed genotypes using data from the 1000 Genomes Project<sup><xref rid="R15" ref-type="bibr">15</xref></sup>. These approaches identified a second cluster of strongly correlated SNPs (r<sup>2</sup>>0.90) in a distinct region proximal to the inversion (centered at chromosome 17: 43.5 MB, human genome build 37) that was more significantly associated with the risk of all invasive EOCs (<italic>P</italic>= 10<sup>−9</sup>) and invasive serous EOC specifically (<italic>P</italic>= 10<sup>−10</sup>) than the cluster of identified miRSNPs (<xref rid="F1" ref-type="fig">Fig. 1</xref>). Association results and annotation for SNPs in this second cluster are shown in <xref rid="SD1" ref-type="supplementary-material">Supplementary Table S2</xref>; this cluster includes three directly genotyped SNPs (rs2077606, rs17631303, and rs12942666), with the strongest association observed for rs2077606 among all invasive cases (OR=1.12, 95% CI: 1.08-1.16), <italic>P</italic>=7.8×10<sup>−9</sup>) and invasive serous cases (OR=1.15, 95% CI: 1.12-1.19, <italic>P</italic>=3.9×10<sup>−10</sup>). These SNPs were chosen for genotyping in COGS because they had shown evidence of association as modifiers of EOC risk in BRCA1 gene mutation carriers by the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA)<sup><xref rid="R16" ref-type="bibr">16</xref></sup>. Several imputed SNPs in strong LD (r<sup>2</sup>>0.90) were more strongly associated with risk than their highly correlated genotyped SNPs (<xref rid="SD1" ref-type="supplementary-material">Supplementary Table S2</xref>). This risk-associated region at 17q21.31 is distinct from a previously reported ovarian cancer susceptibility locus at 17q21<sup><xref rid="R17" ref-type="bibr">17</xref></sup>; neither the genotyped or imputed SNPs we report here are strongly correlated (maximum r<sup>2</sup>= 0.01) with SNPs from the 17q21 locus (spanning 46.2-46.5 MB, build 37).</p><p id="P9">Genotype clustering was poor for rs2077606, but clustering was good for its correlated SNP, rs12942666 (r<sup>2</sup>=0.99), and so results for this SNP are presented instead (<xref rid="SD1" ref-type="supplementary-material">Supplementary Fig. S2</xref>; <xref rid="T1" ref-type="table">Table 1</xref>). Subgroup analysis revealed marginal evidence of association for rs12942666 with endometrioid (<italic>P</italic>=0.04), but not mucinous or clear cell EOC subtypes (<xref rid="T1" ref-type="table">Table 1</xref>), and results were consistent across studies (<xref rid="SD1" ref-type="supplementary-material">Supplementary Fig. S4</xref>). Rs12942666 is correlated with the top-ranked miRSNP, rs1052587 (r<sup>2</sup>=0.76) (<xref rid="F1" ref-type="fig">Fig. 1</xref>). To evaluate whether associations observed for rs12942666 and rs1052587 represented independent signals, stepwise logistic regression was used; only rs12942666 was retained in the model. This suggests that the cluster which includes rs12942666 is driving the association with EOC risk that was initially identified through the candidate miRSNPs.</p></sec><sec id="S3"><title>Functional and molecular analyses</title><p id="P10">To evaluate functional evidence for candidate genes, risk-associated SNPs, and regulatory regions at 17q21.31, we examined a one megabase region centered on rs12942666 using a combination of locus specific and genome-wide assays and <italic>in silico</italic> analyses of publicly available datasets, including The Cancer Genome Atlas (TCGA) Project<sup><xref rid="R18" ref-type="bibr">18</xref></sup> (see Methods). Rs12942666 and many of its correlated SNPs lie within introns of Rho GTPase activating protein 27 (<italic>ARHGAP27</italic>) or its neighboring gene, pleckstrin homology domain containing, family M (with RUN domain) member 1 (<italic>PLEKHM1</italic>) (<xref rid="SD1" ref-type="supplementary-material">Supplementary Table S2</xref>). There are another 15 known protein-coding genes within the region: <italic>KIF18B, C1QL1, DCAKD, NMT1, PLCD3, ABCB4, HEXIM1, HEXIM2, FMNL1, C17orf46, MAP3K14, C17orf69, CRHR1, IMP5</italic>, and <italic>MAPT</italic> (<xref rid="F2" ref-type="fig">Fig. 2a</xref>).</p><p id="P11">To evaluate the likelihood that one or more genes within this region represent target susceptibility gene(s), we first analyzed expression, copy number variation, and methylation involving these genes in EOC tissues and cell lines (<xref rid="F2" ref-type="fig">Fig. 2b-g</xref>; <xref rid="SD1" ref-type="supplementary-material">Supplementary Tables S3 and S4</xref>). Most genes showed significantly higher expression (<italic>P</italic><10<sup>−4</sup>) in EOC cell lines versus normal ovarian cancer-precursor tissues (OCPTs); <italic>ARHGAP27</italic> showed the most pronounced difference in gene expression between cancer and normal cells (<italic>P</italic>=10<sup>−16</sup>) (<xref rid="F2" ref-type="fig">Fig. 2b</xref> and <xref rid="SD1" ref-type="supplementary-material">Supplementary Table S3</xref>). For nine genes, we also found overexpression in primary high-grade serous (HGS) EOC tumors versus normal ovarian tissue in at least one of two publicly available datasets, The Cancer Genome Atlas (TCGA) of 568 tumors <sup><xref rid="R18" ref-type="bibr">18</xref></sup>and/or the Gene Expression Omnibus (GEO) series GSE18520 dataset consisting of 53 tumors<sup><xref rid="R19" ref-type="bibr">19</xref></sup> (<xref rid="F2" ref-type="fig">Fig. 2c</xref> and <xref rid="SD1" ref-type="supplementary-material">Supplementary Table S3</xref>). Analysis of DNA copy number variation in TCGA revealed frequent loss of heterozygosity in this region rather than gains (<xref rid="SD1" ref-type="supplementary-material">Supplementary Fig. 5a-b; Supplementary Methods</xref>). We observed significant hypomethylation (<italic>P</italic><0.01) in ovarian tumors compared to normal tissue for <italic>DCAKD, PLCD3, ACBD4, FMNL1</italic>, and <italic>PLEKHM1</italic> (<xref rid="F2" ref-type="fig">Fig. 2d</xref> and <xref rid="SD1" ref-type="supplementary-material">Supplementary Table S4</xref>), which is consistent with the overexpression observed for <italic>DCAKD, PLCD3</italic>, and <italic>FMNL1</italic>. Taken together, these data suggest that the mechanism underlying overexpression may be epigenetic rather than based on copy number alterations.</p><p id="P12">We evaluated associations between genotypes for the top risk SNP rs12942666 (or a tagSNP) and expression of all genes in the region (expression quantitative trait locus (eQTL) analysis) in normal OCPTs, lymphoblastoid cell lines (LCLs), and primary tumors from TCGA. We observed significant eQTL associations (P<0.05) in normal OCPTs only for <italic>ARHGAP27</italic> (<italic>P</italic>=0.04) (<xref rid="F2" ref-type="fig">Fig. 2e</xref>; <xref rid="SD1" ref-type="supplementary-material">Supplementary Table S3</xref>). Because rs12942666 was not genotyped in tissues analyzed in TCGA, we used data for its correlated SNP rs2077606 (r<sup>2</sup>=0.99) to evaluate eQTLs in tumor tissues. Rs2077606 genotypes were strongly associated with <italic>PLEKHM1</italic> expression in primary HGS-EOCs (<italic>P</italic>=1×10<sup>−4</sup>) (<xref rid="F2" ref-type="fig">Fig. 2f</xref>; <xref rid="SD1" ref-type="supplementary-material">Supplementary Table S3</xref>). We also detected associations between rs12942666 (and rs2077606) genotypes and methylation for <italic>PLEKHM1</italic> and <italic>CRHR1</italic> in primary tumors (<italic>P</italic>=0.020 and 0.001, respectively) using methylation quantitative trait locus (mQTL) analyses (<xref rid="F2" ref-type="fig">Fig. 2g</xref>; <xref rid="SD1" ref-type="supplementary-material">Supplementary Table S4</xref>). Finally, the Catalogue of Somatic Mutations in Cancer (COSMIC) database <sup><xref rid="R20" ref-type="bibr">20</xref></sup> showed that nine genes in the region, including <italic>PLEKHM1</italic>, have functionally significant mutations in cancer, although for most genes mutations were not reported in ovarian carcinomas (<xref rid="SD1" ref-type="supplementary-material">Supplementary Table S3</xref>).</p><p id="P13">Taken together, these data suggest that several genes at the 17q21.31 locus may play a role in EOC development. The risk-associated SNPs we identified fall within non-coding DNA, suggesting the functional SNP(s) may be located within an enhancer, insulator, or other regulatory element that regulates expression of one of the candidate genes we evaluated. One hypothesis emerging from these molecular analyses is that rs12942666 (or a correlated SNP) mediates regulation of <italic>PLEKHM1</italic>, a gene implicated in osteopetrosis and endocytosis <sup><xref rid="R21" ref-type="bibr">21</xref></sup> and/or <italic>ARHGAP27</italic>, a gene that may promote carcinogenesis through dysregulation of Rho/Rac/Cdc42-like GTPases <sup><xref rid="R22" ref-type="bibr">22</xref></sup>. To identify the most likely candidate for being the causal variant at 17q21.31, we compared the difference between log-likelihoods generated from un-nested logistic regression models for rs12942666 and each of 198 SNPs in a 1 MB region featured in <xref rid="SD1" ref-type="supplementary-material">Supplementary Table 2</xref>. As expected, the log likelihoods were very similar due to the strong LD; no SNPs emerged as having a likelihood ratio greater than 20 for being the causal variant.</p><p id="P14">To explore the possible functional significance of rs12942666 and strongly correlated variants (r<sup>2</sup>>0.80), we then generated a map of regulatory elements around rs12942666 using ENCODE data and FAIRE-seq analysis of OCPTs (<xref rid="SD1" ref-type="supplementary-material">Supplementary Methods</xref>). We observed no evidence of putative regulatory elements coinciding with rs12942666 or correlated SNPs (<xref rid="F3" ref-type="fig">Fig. 3a</xref>). A map of regulatory elements in the entire 1 MB region can be seen in <xref rid="SD1" ref-type="supplementary-material">Supplementary Fig. 5c-f</xref>. We subsequently used <italic>in silico</italic> tools (ANNOVAR<sup><xref rid="R23" ref-type="bibr">23</xref></sup>, SNPinfo<sup><xref rid="R24" ref-type="bibr">24</xref></sup>, and SNPnexus<sup><xref rid="R25" ref-type="bibr">25</xref></sup>) to evaluate the putative function of possible causal SNPs (<xref rid="SD1" ref-type="supplementary-material">Supplementary Methods</xref>). Of 50 SNPs with possible functional roles, more than 30 reside in putative transcription factor binding sites (TFBS) within or near <italic>PLEKHM1</italic> or <italic>ARHGAP27</italic>; 12 SNPs may affect methylation or miRNA binding, and two are non-synonymous coding variants predicted to be of no functional significance (<xref rid="SD1" ref-type="supplementary-material">Supplementary Table S2</xref>).</p><p id="P15">Since most of the top-ranked 17q21.31 SNPs with putative functions (including two of the top directly genotyped SNPs, rs2077606 and rs17631303), are predicted to lie in TFBS (<xref rid="SD1" ref-type="supplementary-material">Supplementary Table S2</xref>), we used the <italic>in silico</italic> tool, JASPAR <sup><xref rid="R26" ref-type="bibr">26</xref></sup> to further examine TFBS coinciding with these SNPs. Two SNPs scored highly in this analysis (<xref rid="SD1" ref-type="supplementary-material">Supplementary Table S5</xref>); the first, rs12946900, lies in a GAGGAA motif and canonical binding site for <italic>SPIB</italic>, an Ets family member<sup><xref rid="R27" ref-type="bibr">27</xref></sup>. Ets factors have been implicated in the development of ovarian cancer and other malignancies<sup><xref rid="R28" ref-type="bibr">28</xref></sup>, but little evidence supports a specific role for <italic>SPIB</italic> in EOC etiology. The second hit was for rs2077606, which lies in an E-box motif CACCTG at the canonical binding site for <italic>ZEB1</italic> (chr. 10p11.2), a zinc-finger E-box binding transcription factor that represses E-cadherin<sup><xref rid="R29" ref-type="bibr">29</xref>,<xref rid="R30" ref-type="bibr">30</xref></sup> and contributes to epithelial-mesenchymal transition in EOCs <sup><xref rid="R31" ref-type="bibr">31</xref></sup>.</p><p id="P16">We analyzed expression of <italic>SPIB</italic> and <italic>ZEB1</italic> in primary ovarian cancers using TCGA data; we found no significant difference in <italic>SPIB</italic> expression in tumors compared to normal tissues (<xref rid="F3" ref-type="fig">Fig. 3bi</xref>). In contrast, <italic>ZEB1</italic> expression was significantly lower in primary HGS-EOCs compared to normal tissues (<italic>P</italic>=0.005) (<xref rid="F3" ref-type="fig">Fig. 3bii</xref>). We validated this finding using qPCR analysis in 123 EOC and OCPT cell lines (<italic>P</italic>=8.8 ×10<sup>−4</sup>) (<xref rid="F3" ref-type="fig">Fig. 3biii</xref>). Since rs2077606 lies within an intron of <italic>PLEKHM1</italic>, this gene is a candidate target for <italic>ZEB1</italic> binding at this site. Our eQTL analysis also suggests <italic>ARHGAP27</italic> is a strong candidate <italic>ZEB1</italic> target at this locus; <italic>ARHGAP27</italic> expression is highest in OCPT cell lines carrying the minor allele of rs2077606 (<italic>P</italic>=0.034) (<xref rid="F3" ref-type="fig">Figure 3ci</xref>). Although we observed no eQTL associations between rs2077606 and <italic>ZEB1</italic> expression in LCLs (<xref rid="F3" ref-type="fig">Figure 3cii</xref>), we found evidence of eQTL between rs2077606 and <italic>ZEB1</italic> expression in HGS-EOCs (<italic>P</italic>=0.045) (<xref rid="F3" ref-type="fig">Figure 3ciii</xref>). <italic>ZEB1</italic> binding at the site of the common allele is predicted to repress gene expression while loss of <italic>ZEB1</italic> binding conferred by the minor allele may enable expression of <italic>ARHGAP27</italic>, consistent with the eQTL association in OCPTs (<xref rid="F3" ref-type="fig">Fig. 3ci</xref>). Although this data supports a repressor role for <italic>ZEB1</italic> in EOC development and suggests ARHGAP27 may be a functional target of rs2077606 (or a correlated SNP) in OCPTs through trans-regulatory interactions with <italic>ZEB1</italic>, it is important to investigate additional hypotheses as we continue to narrow down the list of target susceptibility genes, SNPs, and regulatory mechanisms that contribute to EOC susceptibility at this locus.</p></sec></sec><sec sec-type="discussion" id="S4"><title>Discussion</title><p id="P17">The present study represents the largest, most comprehensive investigation of the association between putative miRSNPs in the 3′ untranslated region and cancer risk. This and the systematic follow-up to evaluate associations with EOC risk for non-miRSNPs in the region identified 17q21.31 as a new susceptibility locus for EOC. Although the miRSNPs identified here may have some biological significance, our findings suggest that other types of variants in non-coding DNA, especially non-miRSNPs at the 17q21.31 locus, are stronger contributors to EOC risk. It is possible, however, that highly significant miRSNPs exist that were not identified in our study because a) they were not pre-selected for evaluation (i.e. they do not reside in a binding site involving miRNAs or genes with known relevance to EOC, or they reside in regions other than the 3′UTR<sup><xref rid="R3" ref-type="bibr">3</xref>,<xref rid="R4" ref-type="bibr">4</xref></sup>) and/or b) they were very rare and could not be designed or detected with our genotyping platform and sample size, respectively. Despite these limitations, the homogeneity between studies of varying designs and populations in the OCAC and the genome-wide levels of statistical significance imply that all detected associations are robust. Furthermore, molecular correlative analyses of genes within the region suggest that cis-acting genetic variants influencing non-coding DNA regulatory elements, miRNAs, and/or methylation underlie disease susceptibility at the 17q21.31 locus. Finally, these studies point to a subset of candidate genes (i.e. <italic>PLEKHM1</italic>, <italic>ARHGAP27</italic>) and transcription factors (i.e. ZEB1) that may influence EOC initiation and development.</p><p id="P18">This novel locus is one of eleven loci now identified that contains common genetic variants conferring low penetrance susceptibility to EOC in the general population <sup><xref rid="R17" ref-type="bibr">17</xref>,<xref rid="R32" ref-type="bibr">32</xref>,<xref rid="R33" ref-type="bibr">33</xref>,<xref rid="R34" ref-type="bibr">34</xref></sup>. Genetic variants at several of these loci influence risks of more than one cancer type, suggesting that several cancers may share common mechanisms. For example, alleles at 5p15.33 and 19p13.1 are associated with estrogen-receptor-negative breast cancer and serous EOC susceptibility <sup><xref rid="R32" ref-type="bibr">32</xref>,<xref rid="R35" ref-type="bibr">35</xref></sup>, and variants at 8q24 are associated with risk of EOC and other cancers <sup><xref rid="R17" ref-type="bibr">17</xref>,<xref rid="R36" ref-type="bibr">36</xref></sup>. Genetic variation at 17q21.31 is also associated with frontotemporal dementia-spectrum disorders, Parkinson's disease, developmental delay, and alopecia <sup><xref rid="R37" ref-type="bibr">37</xref>-<xref rid="R42" ref-type="bibr">42</xref></sup>. Through COGS, the CIMBA also recently identified 17q21.31 variants as modifying EOC risk in <italic>BRCA1</italic> and <italic>BRCA2</italic> carriers (<italic>P</italic><10<sup>−8</sup> in <italic>BRCA1/2</italic> combined)<sup><xref rid="R16" ref-type="bibr">16</xref></sup>. In particular, rs17631303, which is perfectly correlated with rs2077606 and rs12942666, was among the top-ranking SNPs detected by CIMBA<sup><xref rid="R16" ref-type="bibr">16</xref></sup>. Consistent with our findings, CIMBA also provide data that suggests EOC risk is associated with altered expression of one or more genes in the 17q21.31 region<sup><xref rid="R16" ref-type="bibr">16</xref></sup>. Thus, results from this large-scale collaboration support a role for this locus in both <italic>BRCA1/2</italic> and non-<italic>BRCA1/2</italic> mediated EOC development. Before these findings can be integrated with variants from other confirmed loci and non-genetic factors to predict women at greatest risk of developing EOC and provide options for medical management of these risks, continued efforts will be needed to fine map the 17q21.31 region and to fully characterize the functional and mechanistic effects of potential causal SNPs in disease etiology and development.</p></sec><sec sec-type="methods" id="S5"><title>Methods</title><sec id="S6"><title>Study population</title><p id="P19">Forty-three individual OCAC studies contributed samples and data to the COGS initiative. Nine of the 43 participating studies were case-only (GRR, HSK, LAX, ORE, PVD, RMH, SOC, SRO, UKR); cases from these studies were pooled with case-control studies from the same geographic region. The two national Australian case-control studies were combined into a single study to create 34 case-control sets. Details regarding the 43 participating OCAC studies are summarized in <xref rid="SD1" ref-type="supplementary-material">Supplementary Table S1</xref>. Briefly, cases were women diagnosed with histologically confirmed primary EOC (invasive or low malignant potential), fallopian tube cancer, or primary peritoneal cancer ascertained from population- and hospital-based studies and cancer registries. The majority of OCAC cases (>90%) do not have a family history of ovarian or breast cancer in a first-degree relative, and most have not been tested for <italic>BRCA1/2</italic> mutations as part of their parent study. Controls were women without a current or prior history of ovarian cancer with at least one ovary intact at the reference date. All studies had data on disease status, age at diagnosis/interview, self-reported racial group, and histologic subtype. Most studies frequency-matched cases and controls on age-group and race.</p></sec><sec id="S7"><title>Selection of Candidate Genes and SNPs</title><p id="P20">To increase the likelihood of identifying miRSNPs with biological relevance to EOC, we reviewed published literature and consulted public databases to generate two lists of candidate genes: 1) 55 miRNAs reported to be deregulated in EOC tumors compared to normal tissue in at least one study <sup><xref rid="R43" ref-type="bibr">43</xref>-<xref rid="R46" ref-type="bibr">46</xref></sup>, and 2) 665 genes implicated in the pathogenesis of EOC through gene expression analyses <sup><xref rid="R47" ref-type="bibr">47</xref>,<xref rid="R48" ref-type="bibr">48</xref></sup>, somatic mutations <sup><xref rid="R49" ref-type="bibr">49</xref></sup>, or genetic association studies <sup><xref rid="R50" ref-type="bibr">50</xref>,<xref rid="R51" ref-type="bibr">51</xref></sup>. Many genes were identified through the Gene Prospector database<sup><xref rid="R51" ref-type="bibr">51</xref></sup>, a web-based application that selects and prioritizes potential disease-related genes using a highly curated, up-to-date database of genetic association studies.</p><p id="P21">Using each candidate gene list as input, we identified putative sites of miRNA:mRNA binding with the computational prediction algorithms TargetScan version 5.1 <sup><xref rid="R10" ref-type="bibr">10</xref>,<xref rid="R11" ref-type="bibr">11</xref></sup> and PicTar <sup><xref rid="R12" ref-type="bibr">12</xref>,<xref rid="R13" ref-type="bibr">13</xref></sup> and <xref rid="SD1" ref-type="supplementary-material">Supplementary Methods</xref>). Each algorithm generated start and end coordinates for regions of miRNA binding, and database SNP (dbSNP)<sup><xref rid="R52" ref-type="bibr">52</xref></sup> version 129 was mined to identify SNPs falling within the designated binding regions. Of 3,246 unique miRSNPs that were identified, 1102 obtained adequate design scores using Illumina's Assay Design Tool. The majority (n=1085, 98.5%) of the 1102 SNPs resided in predicted sites of miRNA binding (and therefore represent miRSNPs), while the remainder (n=17) are tagSNPs (r<sup>2</sup> > 0.80) for miRSNPs that were not designable or had poor to moderate design scores. Ninety nine of the 1102 SNPs failed during custom assay development, leaving a total of 1,003 SNPs that were designed and genotyped.</p></sec><sec id="S8"><title>Genotyping and QC</title><p id="P22">The candidate miRSNPs selected for the current investigation were genotyped using a custom Illumina Infinium iSelect Array as part of the international Collaborative Oncological Gene-environment Study (COGS), an effort to evaluate 211,155 genetic variants for association with the risk of ovarian, breast, and prostate cancer. Samples and data were included from several consortia, including OCAC, the Breast Cancer Association Consortium (BCAC), the Consortium of Investigators of Modifiers of <italic>BRCA1/2</italic> (CIMBA), and the Prostate Cancer Association Group to Investigate Cancer- Associated Alterations in the Genome (PRACTICAL). Although one of the primary goals of COGS was to replicate and fine-map findings from pooled genome-wide association studies (GWAS) from each consortia, this effort also aimed to genotype candidate SNPs of interest (such as the miRSNPs). The genotyping and QC process has been described recently in our report of OCAC's pooled GWAS findings<sup><xref rid="R34" ref-type="bibr">34</xref></sup>. Briefly, COGS genotyping was conducted at six centers, two of which were used for OCAC samples: McGill University and Génome Québec Innovation Centre (Montréal, Canada) (n=19,806) and Mayo Clinic Medical Genomics Facility (n=27,824). Each 96-well plate contained 250ng genomic DNA (or 500 ng whole genome-amplified DNA). Raw intensity data files were sent to the COGS data coordination center at the University of Cambridge for genotype calling and QC using the GenCall algorithm.</p><sec id="S9"><title>Sample QC</title><p id="P23">One thousand two hundred and seventy three OCAC samples were genotyped in duplicate. Genotypes were discordant for greater than 40 percent of SNPs for 22 pairs. For the remaining 1,251 pairs, concordance was greater than 99.6 percent. In addition we identified 245 pairs of samples that were unexpected genotypic duplicates. Of these, 137 were phenotypic duplicates and judged to be from the same individual. We used identity-by-state to identify 618 pairs of first-degree relatives. Samples were excluded according to the following criteria: 1) 1,133 samples with a conversion rate (the proportion of SNPs successfully called per sample) of less than 95 percent; 2) 169 samples with heterozygosity >5 standard deviations from the intercontinental ancestry specific mean heterozygosity; 3) 65 samples with ambiguous sex; 4) 269 samples with the lowest call rate from a first-degree relative pair 5) 1,686 samples that were either duplicate samples that were non-concordant for genotype or genotypic duplicates that were not concordant for phenotype. A total of 44,308 eligible subjects including 18,174 cases and 26,134 controls were available for analysis.</p></sec><sec id="S10"><title>SNP QC</title><p id="P24">The process of SNP selection by the participating consortia has been summarized previously<sup><xref rid="R34" ref-type="bibr">34</xref></sup>. In total, 211,155 SNP assays were successfully designed, including 23,239 SNPs nominated by OCAC. Overall, 94.5% of OCAC-nominated SNPs passed QC. SNPs were excluded if: (1) the call rate was less than 95% with MAF > 5% or less than 99% with MAF < 5% (n=5,201); (2) they were monomorphic upon clustering (n=2,587); (3) p values of HWE in controls were less than 10<sup>−7</sup> (n=2,914); (4) there was greater than 2% discordance in duplicate pairs (n=22); (5) no genotypes were called (n=1,311). Of 1,003 candidate miRSNPs genotyped, 767 passed QC criteria and were available for analysis; the majority of miRSNPs that were excluded were monomorphic (n=158, 67%). Genotype intensity cluster plots were visually inspected for the most strongly associated SNPs.</p></sec></sec><sec id="S11"><title>Population stratification</title><p id="P25">HapMap DNA samples for European (CEU, n=60), African (YRI, n=53) and Asian (JPT+CHB, n=88) populations were also genotyped using the COGS iSelect. We used the program LAMP <sup><xref rid="R53" ref-type="bibr">53</xref></sup> to estimate intercontinental ancestry based on the HapMap (release no. 23) genotype frequency data for these three populations. Eligible subjects with greater than 90 percent European ancestry were defined as European (n=39,773) and those with greater than 80 percent Asian or African ancestry were defined as Asian (n=2,382) or African respectively (n=387). All other subjects were defined as being of mixed ancestry (n=1,766). We then used a set of 37,000 unlinked markers to perform principal components analysis within each major population subgroup. To enable this analysis on very large sample sizes we used an in-house program written in C++ using the Intel MKL libraries for eigenvectors (available at <ext-link ext-link-type="uri" xlink:href="http://ccge.medschl.cam.ac.uk/software/">http://ccge.medschl.cam.ac.uk/software/</ext-link>).</p></sec><sec id="S12"><title>Tests of association</title><p id="P26">We used unconditional logistic regression treating the number of minor alleles carried as an ordinal variable (log-additive model) to evaluate the association between each SNP and EOC risk. Separate analyses were carried out for each ancestry group. The model for European subjects was adjusted for population substructure by including the first 5 eigenvalues from the principal components analysis. African- and Asian- ancestry-specific estimates were obtained after adjustment for the first two components representing each respective ancestry. Due to the heterogeneous nature of EOC, subgroup analysis was conducted to estimate genotype-specific odds ratios for serous carcinomas (the most predominant histologic subtype) and the three other main histological subtypes of EOC: endometrioid, mucinous, and clear cell. Separate analyses were also carried out for each study site, and site-specific ORs were combined using a fixed-effect meta-analysis. The <italic>I<sup>2</sup></italic> test of heterogeneity was estimated to quantify the proportion of total variation due to heterogeneity across studies, and the heterogeneity of odds ratios between studies was tested with Cochran's Q statistic. The R statistical package ‘r-meta’ was used to generate forest plots. Statistical analysis was conducted in PLINK<sup><xref rid="R54" ref-type="bibr">54</xref></sup>.</p></sec><sec id="S13"><title>Imputation of genotypes at 17q21.31</title><p id="P27">To increase genomic coverage, we imputed genotype data for the 17q21.31 region (chr17: 40,099,001-44,900,000, human genome build 37) with IMPUTE2.2 <sup><xref rid="R55" ref-type="bibr">55</xref></sup> using phase 1 haplotype data from the January 2012 release of the 1000 genome project data <sup><xref rid="R15" ref-type="bibr">15</xref></sup>. For each imputed genotype the expected number of minor alleles carried was estimated (as weights). IMPUTE provides estimated allele dosage for SNPs that were not genotyped and for samples with missing data for directly genotyped SNPs. Imputation accuracy was estimated using an r<sup>2</sup>quality metric. We excluded imputed SNPs from analysis where the estimated accuracy of imputation was low (r<sup>2</sup><0.3).</p></sec><sec id="S14"><title>Functional studies and <italic>in silico</italic> analysis of publicly available datasets</title><p id="P28">We performed the following assays for each gene in the one megabase region centered on the most significant SNP at the 17q21.31 locus (see <xref rid="SD1" ref-type="supplementary-material">Supplementary Methods</xref>): gene expression analysis in EOC cell lines (n=51) compared to normal cell lines from ovarian cancer precursor tissues (OCPTs)<sup><xref rid="R56" ref-type="bibr">56</xref></sup>, including ovarian surface epithelial cells (OSECs) and fallopian tube secretory epithelial cells (FTSECs) (n=73), and CpG island methylation analysis in high grade serous ovarian cancer (HGS-EOC) tissues (n=106) and normal tissues (n=7). Genes in the region were also evaluated <italic>in silico</italic> by mining publicly available molecular data generated for primary EOCs and other cancer types, including The Cancer Genome Atlas (TCGA) analysis of 568 HGS EOCs<sup><xref rid="R18" ref-type="bibr">18</xref></sup>, the Gene Expression Omnibus series GSE18520 dataset of 53 HGS EOCs <sup><xref rid="R19" ref-type="bibr">19</xref></sup>, and the Catalogue Of Somatic Mutations In Cancer (COSMIC) database<sup><xref rid="R20" ref-type="bibr">20</xref></sup>.</p><p id="P29">We used these data to 1) compare gene expression between a) EOC cell lines and normal cell lines and b) tumor tissue and normal tissue from TCGA, 2) compare gene methylation status in HGS-EOCs and normal tissue, 3) conduct gene expression quantitative trait locus (eQTL) analyses to evaluate genotype-gene expression associations in normal OCPTs, lymphoblastoid cells, and HGS-EOCs, and 4) conduct methylation quantitative trait locus (mQTL) analyses in HGS-EOCs to evaluate genotype-gene methylation associations. Data from ENCyclopedia Of DNA Elements (ENCODE) <sup><xref rid="R57" ref-type="bibr">57</xref></sup> were used to evaluate the overlap between regulatory elements in non-coding regions and risk-associated SNPs. ENCODE describes regulatory DNA elements (e.g. enhancers, insulators and promotors) and non-coding RNAs (e.g. miRNAs, long non-coding and piwi-interacting RNAs) that may be targets for susceptibility alleles. However, ENCODE does not include data for EOC associated tissues, and activity of such regulatory elements often varies in a tissue specific manner <sup><xref rid="R57" ref-type="bibr">57</xref>,<xref rid="R58" ref-type="bibr">58</xref></sup>. Therefore, we profiled the spectrum of non-coding regulatory elements in OSECs and FTSECs using a combination of formaldehyde assisted isolation of regulatory elements sequencing (FAIRE-seq) and RNA sequencing (RNA-seq) (<xref rid="SD1" ref-type="supplementary-material">Supplementary Methods</xref>).</p></sec></sec><sec sec-type="supplementary-material" id="S15"><title>Supplementary Material</title><supplementary-material content-type="local-data" id="SD1"><label>1</label><media xlink:href="NIHMS447293-supplement-1.pdf" mimetype="application" mime-subtype="pdf" orientation="portrait" xlink:type="simple" id="d37e2989" position="anchor"></media></supplementary-material></sec></body><back><ack id="S16"><p>We thank all the individuals who took part in this study 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 LaBoissière and F Robidoux (McGill University and Génome Québec Innovation Centre); U. Eilber and T. Koehler (GER); L. Gacucova (HMO); P. Schu¨rmann, 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); 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).</p><p>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).</p><p>This study made use of 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 <ext-link ext-link-type="uri" xlink:href="http://www.wtccc.org.uk/">http://www.wtccc.org.uk/</ext-link>. 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 <ext-link ext-link-type="uri" xlink:href="http://cancergenome.nih.gov/">http://cancergenome.nih.gov/</ext-link>.</p><p>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. BK holds an American Cancer Society Early Detection Professorship (SIOP-06-258-01-COUN). LEK is supported by a Canadian Institutes of Health Research Investigator award (MSH-87734). A.C.A. is Cancer Research-UK Senior Cancer Research Fellow.</p><p>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-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-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, R37-CA70867, R01-CA83918, U01-CA069417, U01-CA071966, P30-CA15083, PSA 042205, and Intramural research funds); the US Army Medical Research and Materiel Command (DAMD17-98-1-8659, DAMD17-01-1-0729, DAMD17-02-1-0666, DAMD17-02-1-0669, W81XWH-10-1-02802); 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-Württemberg 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.</p><p>Access to genotype data for SNPs that were not nominated by OCAC was provided by FJC and ACA on behalf of CIMBA BRCA1 GWAS investigators and was funded by the US National Cancer Institute (R01 CA128978) and U.S. Department of Defense Ovarian Cancer Idea award (W81XWH-10-1-0341). CIMBA BRCA1 GWAS investigators include: Irene L. Andrulis, Ontario Cancer Genetics Network, Cancer Care Ontario and Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Canada; Trinidad Caldes, Molecular Oncology Laboratory, Hospital Clínico San Carlos, Madrid, Spain; Maria Adelaide Caligo, Section of Genetic Oncology, University Hospital of Pisa, Pisa, Italy; Olga Sinilnikova for GEMO Study Collaborators, Cancer Genetics Network “Groupe Genetique et Cancer”, Federation Nationale des Centres de Lutte Contre le Cancer, Lyon, France; Thomas V. O. Hansen, Genomic Medicine, Department of Clinical Biochemistry, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark; Matti Rookus and Frans Hogervorst for HEBON Investigators, Department of Epidemiology, The Netherlands Cancer Institute, Amsterdam, The Netherlands; Anna Jakubowska and Jan Lubinski, International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland; Susan Peock for EMBRACE Investigators, Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Strangeways Research Laboratory, Worts Causeway, Cambridge, United Kingdom; Georgia Chenevix-Trench for kConFab Investigators, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia; BCFR Investigators, Breast Cancer Family Registry, Epidemiology and Genetics Research Program, DCCPS, National Cancer Institute, Rockville, Maryland, USA; Katherine L. Nathanson and Susan Domchek, Departments of Medicine and Medical Genetics and Abramson Cancer Center, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA; Heli Nevanlinna, Department of Obstetrics and Gynecology, Helsinki University Central Hospital, Helsinki, Finland; Kenneth Offit, Memorial Sloan Kettering Cancer Center, New York, New York, USA; Ana Osorio and Javier Benitez, Human Genetics Group, Human Cancer Genetics Programme, Spanish National Cancer Centre, Madrid, Spain; Paolo Radice for CONSIT investigators, Unit of Molecular Bases of Genetic Risk and Genetic Testing, Department of Preventive and Predictive Medicine, Fondazione IRCCS Istituto Nazionale Tumori (INT); IFOM, Fondazione Istituto FIRC di Oncologia Molecolare, Milan, Italy; Christian F. Singer, Division of Special Gynecology, Medical University of Vienna, Vienna, Austria; SWE-BRCA Investigators, Karolinska University Hospital, Stockholm, Sweden; Rita Schmutzler for GC-HBOC investigators, Center of Familial Breast and Ovarian Cancer, Department of Obstetrics and Gynaecology and Center for Integrated Oncology (CIO), University of Cologne, Cologne, Germany; Andrew Godwin, Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, Kansas; Ignacio Blanco and Conxi Lazaro, Hereditary Cancer Program, Instituto Catalan de Oncología, Barcelona, Spain; Marco Montagna, Immunology and Molecular Oncology Unit, Istituto Oncologico Veneto IOV–IRCCS, Padua, Italy; Mary S. Beattie, Cancer Risk Program, Departments of Medicine, Epidemiology, and Biostatistics, University of California at San Francisco, San Francisco, California, USA; Antonis C. Antoniou and Douglas F. Easton, Centre for Cancer Genetic Epidemiology, University of Cambridge, Cambridge, United Kingdom; Fergus J. Couch, Mayo Clinic, Rochester, Minnesota, USA.</p></ack><fn-group><fn id="FN3" fn-type="con"><p>Author Contributions: These authors contributed equally to this work: JPW, KL, and HCS, and ANAM, TAS, and SAG. Writing group: JPW, KL, HCS, AV, ANAM, SAG, TAS, ELG, BLF, SJR, and PDPP. All authors read and approved the final version of the manuscript.</p><p>Provision of data and/or samples from contributing studies and institutions: JPW, KL, HCS, AV, JT, ZC, H-YL, YAC, Y- YT, XQ, SJR, RK, JL, NL, MCL, KA, HA-C, NA, AA, SMA, FB, LB, EB, JBS, MWB, MJB, GB, NB, LAB, ABW, RB, RB, QC, IC, JCC, SC, GCT, JQC, MSC, GAC, LSC, FJC, DWC, JMC, ADM, ED, JAD, TD, AdB, MD, DFE, DE, RE, ABE, PAF, DAF, JMF, MGC, AGM, GGG, RMG, JGB, MTG, MG, BG, JG, PH, MH, PH, FH, PH, MH, CH, EH, SH, AJ, AJ, HJ, KK, BYK, SBK, LEK, LAK, FK, GK, CK, SKK, JK, DL, SL, JML, NDL, AL, DAL, DL, JL, BKL, JL, KHL, JL, GL, LFAGM, KM, VM, JRM, UM, FM, KBM, TN, SAN, LN, RBN, HN, SN, HN, KO, SHO, IO, JP, CLP, TP, LMP, MCP, EMP, PR, SPR, HAR, LRR, MAR, AR, IR, IKR, HBS, IS, GS, VS, X-OS, YBS, WS, HS, MCS, BS, DS, RS, S-HT, KLT, DCT, PJT, SST, AMvA, IV, RAV, DV, AV, SW-G, RPW, NW, ASW, EW, LRW, BW, YLW, AHW, Y-BX, HPY, WZ, AZ, FZ, CMP, EI, JMS, AB, BLF, ELG, PDDP, ANAM, TAS, and SAG.</p><p>Collated and organized 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pub-id-type="pmid">21441907</pub-id></element-citation></ref><ref id="R58"><label>58</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Heintzman</surname><given-names>ND</given-names></name><etal></etal></person-group><article-title>Histone modifications at human enhancers reflect global cell-type-specific gene expression</article-title><source>Nature</source><volume>459</volume><fpage>108</fpage><lpage>112</lpage><year>2009</year><pub-id pub-id-type="pmid">19295514</pub-id></element-citation></ref></ref-list></back><floats-group><fig id="F1" orientation="portrait" position="float"><label>Figure 1</label><caption><title>Regional association plot for genotyped and imputed SNPs at 17q21.31</title><p>The middle portion of the plot contains the region of the inversion polymorphism (ch 17: 43,624,578-44,525,051, hg build 37), with the four blue dots representing the candidate miRSNPs (rs4640231, rs1052587, and rs17574361) and the tagSNP, rs916793. rs1052587 in the 3′UTR of <italic>MAPT</italic> has the strongest signal (P=4.6×10<sup>−8</sup>) among the miRSNPs. The cluster on the left side of the plot (around 43.5 MB) contains highly correlated SNPs (r<sup>2</sup>=0.99), including three directly genotyped intronic SNPs, rs2077606 and rs17631303 in <italic>PLEKHM1</italic> (P=3.9 × 10<sup>−10</sup> and P=4.7 × 10<sup>−10</sup>, respectively), and rs12942666 in ARHGAP27 (P=1.0 × 10<sup>−9</sup>). The linkage disequilibrium between each plotted SNP and the top-ranked SNP in the region with the best clustering, rs12942666, is depicted by the color scheme; the deeper the color red, the stronger the correlation between the plotted SNP and rs12942666. The top miRSNP, rs1052587, is moderately correlated (r<sup>2</sup>=0.76) with rs2077606, rs17631303, and rs12942666 in our study population. (n=8,371 invasive serous cases and n= 23,491 controls, of European ancestry).</p></caption><graphic xlink:href="nihms447293f1"></graphic></fig><fig id="F2" orientation="portrait" position="float"><label>Figure 2</label><caption><title>Expression and methylation analyses at the 17q21.31 ovarian cancer susceptibility locus</title><p><bold>(a)</bold> Genomic map and LD structure. The location and approximate size of 17 known protein coding genes (grey) and one microRNA (blue) in the region are shown relative to the location of rs12942666. Orange indicates the location of the inversion polymorphism, and green indicates the region outside the inversion.</p><p><bold>(b)</bold> Gene expression (EOC and normal cell lines). Gene expression analysis in Epithelial Ovarian Cancer (EOC) cell lines (T; n=51) compared to normal ovarian surface epithelial cells (OSECs) and fallopian tube secretory epithelial cells (FTSEC) (N; n=73) (* p<0.05, **p<0.01, ***p<0.001).</p><p><bold>(c)</bold> Gene expression (Primary EOCs and Normal Tissue). Boxplots of The Cancer Genome Atlas (TCGA) Affymetrix U133A-array based gene expression in primary high-grade serous ovarian tumors (T; n=568) and normal fallopian tube tissues (N; n=8). Where data were not available in TCGA, gene expression data from the Gene Expression Omnibus series GSE18520 dataset containing 53 high-grade serous tumors and 10 normal ovarian tissues are shown (indicated by a red asterisk).</p><p><bold>(d)</bold> Methylation (Primary Tumors and Normal Tissue). Methylation analysis of 106 high-grade serous ovarian tumors compared to normal ovarian tissues (n=7). Methylation data were generated for CpG site(s) associated with each gene using the Illumina 450 methylation array. Pairwise analysis of methylation for an individual CpG for each gene is based on the CpG with most significant inverse relationship to gene expression (i.e. cis negative), for a subset of 43 tumors having available gene expression data. Statistically significant cis-negative probes are indicated by a red open circle.</p><p><bold>(e)</bold> Expression quantitative trait locus (eQTL) analysis (OSECs/FTSECs). eQTL analysis comparing expression for each gene to genotype for the most statistically significant SNP at 17q21.31 (rs12942666), for 73 normal OSEC/FTSEC lines. Data are presented as box plots comparing expression levels in cases carrying rare homozygotes/heterozygotes, with cases homozygous for the common allele.</p><p><bold>(f)</bold> Expression quantitative trait locus (eQTL) analysis (Primary EOCs). eQTL analysis comparing expression for each gene to genotype using level 3 gene expression profiling data from Agilent 244K custom arrays and level 2 genotype data from the Illumina 1M-Duo BeadChip for 568 high-grade serous ovarian cancer patients from TCGA. In all panels * p<0.05, **p<0.01, *** p<0.001. Grey X's indicate data not available. Here, genotype data for rs2077606 is used (rather than rs12942666) because rs12942666 was not genotyped in the TCGA dataset.</p><p><bold>(g)</bold> Methylation quantitative trait locus (mQTL) analysis (Primary EOCs). mQTL analysis showing methylation status in 227 high-grade serous EOCs relative to rs12942666 genotype.</p></caption><graphic xlink:href="nihms447293f2"></graphic></fig><fig id="F3" orientation="portrait" position="float"><label>Figure 3</label><caption><title>eQTL associations between the rs2077606 susceptibility SNP at 17q21</title><p><bold>(a)</bold> Analysis of the chromatin landscape at <italic>ARHGAP27</italic> and <italic>PLEKHM1</italic> in normal ovarian surface epithelial and fallopian tube secretory epithelial cells (OSECs/FTSECs) by formaldehyde assisted isolation of regulatory elements sequencing (FAIRE-seq). Alignment with ENCODE FAIRE-seq tracks (shown) and ChIP-seq tracks (not shown) from non-EOC related cell lines reveals open chromatin peaks corresponding to (a) promoters (b) CTCF insulator binding sites and (c) H3K4me3 signals, suggestive of a dynamic regulatory region. An H3K4me3 signal at a coding <italic>ARHGAP27</italic> mRNA variant (c) located between the genes is highly pronounced in OSEC/FTSEC, suggesting tissue-specific expression and function. Several of the top-ranking SNPs fall within transcription factor binding sites (TFFS) (<xref rid="SD1" ref-type="supplementary-material">Supplementary Table S2</xref>). rs12942666 did not coincide with TFBS, but tightly linked SNPs, rs12946900 and rs2077606 fell within predicted binding sites for SPIB and ZEB1, respectively.</p><p><bold>(b)</bold> We analyzed the expression of <italic>SPIB</italic> and <italic>ZEB1</italic> in primary high-grade serous tumors from TCGA and found (i) no significant change in SPIB expression but (ii) significant down-regulation of <italic>ZEB1</italic> in tumors compared to normal tissues. (iii) QPCR analysis of <italic>ZEB1</italic> expression in 73 OCPT and 50 EOC cell lines replicated the finding that <italic>ZEB1</italic> expression is lower in cancer cell lines compared to normal precursor tissues. (c) eQTL analysis in OSECs/FTSECs for different alleles of rs2077606. There was a (i) significant eQTL for <italic>ARHGAP27</italic>, with the minor (A) allele being associated with increased <italic>ARHGAP27</italic> expression (<italic>P</italic>=0.034), (ii) no evidence of an association between rs2077606 genotypes and <italic>ARHGAP27</italic> expression in lymphoblastoid cell lines suggesting this association may be tissue-specific. (iii) We observed a borderline significant eQTL association between <italic>ZEB1</italic> mRNA and rs2077606 in tumors from TCGA, with the minor risk allele also associated with lower expression.</p></caption><graphic xlink:href="nihms447293f3"></graphic></fig><table-wrap id="T1" position="float" orientation="landscape"><label>Table 1</label><caption><title>Tests of association by histological subtype for directly genotyped and imputed SNPs at 17q21.31 most strongly associated with invasive epithelial ovarian cancer risk among Europeans</title></caption><table frame="hsides" rules="groups"><thead><tr><th valign="middle" align="center" rowspan="1" colspan="1">SNP Major>minor allele allele</th><th valign="middle" align="center" rowspan="1" colspan="1">Coordinate<sup><xref rid="TFN2" ref-type="table-fn">a</xref></sup></th><th valign="middle" align="center" rowspan="1" colspan="1">MAF</th><th valign="middle" align="center" rowspan="1" colspan="1">Subtype</th><th valign="middle" align="center" rowspan="1" colspan="1">Number of cases (versus 23,491 controls)</th><th valign="middle" align="center" rowspan="1" colspan="1">Per-allele OR (95% CI)<sup><xref rid="TFN3" ref-type="table-fn">b</xref></sup></th><th valign="middle" align="left" rowspan="1" colspan="1">P-value</th></tr></thead><tbody><tr><td align="center" valign="middle" rowspan="1" colspan="1">rs1052587<sup><xref rid="TFN4" ref-type="table-fn">c</xref></sup> (T>C)</td><td align="center" valign="middle" rowspan="1" colspan="1">44102604</td><td align="center" valign="middle" rowspan="1" colspan="1">0.22</td><td align="center" valign="middle" rowspan="1" colspan="1">All Invasives</td><td align="center" valign="middle" rowspan="1" colspan="1">14,533</td><td align="center" valign="middle" rowspan="1" colspan="1">1.10 (1.06-1.13)</td><td align="left" valign="middle" rowspan="1" colspan="1">1.9 × 10<sup>−7</sup></td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1"></td><td align="center" valign="middle" rowspan="1" colspan="1"></td><td align="center" valign="middle" rowspan="1" colspan="1"></td><td align="center" valign="middle" rowspan="1" colspan="1">Serous</td><td align="center" valign="middle" rowspan="1" colspan="1">8,371</td><td align="center" valign="middle" rowspan="1" colspan="1">1.12 (1.08-1.17)</td><td align="left" valign="middle" rowspan="1" colspan="1">4.6 × 10<sup>−8</sup></td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1"></td><td align="center" valign="middle" rowspan="1" colspan="1"></td><td align="center" valign="middle" rowspan="1" colspan="1"></td><td align="center" valign="middle" rowspan="1" colspan="1">Endometrioid</td><td align="center" valign="middle" rowspan="1" colspan="1">2,068</td><td align="center" valign="middle" rowspan="1" colspan="1">1.11 (1.04-1.19)</td><td align="left" valign="middle" rowspan="1" colspan="1">5.2 × 10<sup>−3</sup></td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1"></td><td align="center" valign="middle" rowspan="1" colspan="1"></td><td align="center" valign="middle" rowspan="1" colspan="1"></td><td align="center" valign="middle" rowspan="1" colspan="1">Clear Cell</td><td align="center" valign="middle" rowspan="1" colspan="1">1,025</td><td align="center" valign="middle" rowspan="1" colspan="1">0.98 (0.88-1.09)</td><td align="left" valign="middle" rowspan="1" colspan="1">0.68</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1"></td><td align="center" valign="middle" rowspan="1" colspan="1"></td><td align="center" valign="middle" rowspan="1" colspan="1"></td><td align="center" valign="middle" rowspan="1" colspan="1">Mucinous</td><td align="center" valign="middle" rowspan="1" colspan="1">944</td><td align="center" valign="middle" rowspan="1" colspan="1">1.07 (0.96-1.20)</td><td align="left" valign="middle" rowspan="1" colspan="1">0.22</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">rs12942666<sup><xref rid="TFN5" ref-type="table-fn">d</xref></sup> (A>G)</td><td align="center" valign="middle" rowspan="1" colspan="1">43499839</td><td align="center" valign="middle" rowspan="1" colspan="1">0.22</td><td align="center" valign="middle" rowspan="1" colspan="1">All Invasives</td><td align="center" valign="middle" rowspan="1" colspan="1">14,533</td><td align="center" valign="middle" rowspan="1" colspan="1">1.11 (1.07-1.15)</td><td align="left" valign="middle" rowspan="1" colspan="1">3.3 × 10<sup>−8</sup></td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1"></td><td align="center" valign="middle" rowspan="1" colspan="1"></td><td align="center" valign="middle" rowspan="1" colspan="1"></td><td align="center" valign="middle" rowspan="1" colspan="1">Serous</td><td align="center" valign="middle" rowspan="1" colspan="1">8,371</td><td align="center" valign="middle" rowspan="1" colspan="1">1.15 (1.11-1.20)</td><td align="left" valign="middle" rowspan="1" colspan="1">1.0 × 10<sup>−9</sup></td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1"></td><td align="center" valign="middle" rowspan="1" colspan="1"></td><td align="center" valign="middle" rowspan="1" colspan="1"></td><td align="center" valign="middle" rowspan="1" colspan="1">Endometrioid</td><td align="center" valign="middle" rowspan="1" colspan="1">2,068</td><td align="center" valign="middle" rowspan="1" colspan="1">1.10 (1.02-1.18)</td><td align="left" valign="middle" rowspan="1" colspan="1">0.04</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1"></td><td align="center" valign="middle" rowspan="1" colspan="1"></td><td align="center" valign="middle" rowspan="1" colspan="1"></td><td align="center" valign="middle" rowspan="1" colspan="1">Clear Cell</td><td align="center" valign="middle" rowspan="1" colspan="1">1,025</td><td align="center" valign="middle" rowspan="1" colspan="1">1.04 (0.92-1.14)</td><td align="left" valign="middle" rowspan="1" colspan="1">0.61</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1"></td><td align="center" valign="middle" rowspan="1" colspan="1"></td><td align="center" valign="middle" rowspan="1" colspan="1"></td><td align="center" valign="middle" rowspan="1" colspan="1">Mucinous</td><td align="center" valign="middle" rowspan="1" colspan="1">944</td><td align="center" valign="middle" rowspan="1" colspan="1">1.04 (0.92-1.16)</td><td align="left" valign="middle" rowspan="1" colspan="1">0.55</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">rs2960000<sup><xref rid="TFN6" ref-type="table-fn">e</xref></sup> (T>C)</td><td align="center" valign="middle" rowspan="1" colspan="1">43534353</td><td align="center" valign="middle" rowspan="1" colspan="1">0.18</td><td align="center" valign="middle" rowspan="1" colspan="1">All Invasives</td><td align="center" valign="middle" rowspan="1" colspan="1">14,533</td><td align="center" valign="middle" rowspan="1" colspan="1">1.12 (1.08-1.16)</td><td align="left" valign="middle" rowspan="1" colspan="1">4.2 × 10<sup>−9</sup></td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1"></td><td align="center" valign="middle" rowspan="1" colspan="1"></td><td align="center" valign="middle" rowspan="1" colspan="1"></td><td align="center" valign="middle" rowspan="1" colspan="1">Serous</td><td align="center" valign="middle" rowspan="1" colspan="1">8,371</td><td align="center" valign="middle" rowspan="1" colspan="1">1.16 (1.12-1.20)</td><td align="left" valign="middle" rowspan="1" colspan="1">3.3 × 10<sup>−10</sup></td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1"></td><td align="center" valign="middle" rowspan="1" colspan="1"></td><td align="center" valign="middle" rowspan="1" colspan="1"></td><td align="center" valign="middle" rowspan="1" colspan="1">Endometrioid</td><td align="center" valign="middle" rowspan="1" colspan="1">2,068</td><td align="center" valign="middle" rowspan="1" colspan="1">1.12 (1.03-1.20)</td><td align="left" valign="middle" rowspan="1" colspan="1">0.01</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1"></td><td align="center" valign="middle" rowspan="1" colspan="1"></td><td align="center" valign="middle" rowspan="1" colspan="1"></td><td align="center" valign="middle" rowspan="1" colspan="1">Clear Cell</td><td align="center" valign="middle" rowspan="1" colspan="1">1,025</td><td align="center" valign="middle" rowspan="1" colspan="1">1.05 (0.93-1.16)</td><td align="left" valign="middle" rowspan="1" colspan="1">0.44</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1"></td><td align="center" valign="middle" rowspan="1" colspan="1"></td><td align="center" valign="middle" rowspan="1" colspan="1"></td><td align="center" valign="middle" rowspan="1" colspan="1">Mucinous</td><td align="center" valign="middle" rowspan="1" colspan="1">944</td><td align="center" valign="middle" rowspan="1" colspan="1">1.03 (0.90-1.15)</td><td align="left" valign="middle" rowspan="1" colspan="1">0.65</td></tr></tbody></table><table-wrap-foot><fn id="TFN1"><p>Abbreviations: MAF=minor allele frequency in controls; OR=Odds ratio; CI=Confidence intervals</p></fn><fn id="TFN2"><label>a</label><p>Genome build NCBI B37/human genome build 19 assembly.</p></fn><fn id="TFN3"><label>b</label><p>OR and 95% CI per copy of the minor allele, with adjustment for the first five eigenvalues from principal components analysis.</p></fn><fn id="TFN4"><label>c</label><p>rs1052587 is the most statistically significant miRNA binding site SNP among all invasives and serous; it resides in a putative miRNA binding site between microtubule-associated protein tau (<italic>MAPT</italic>) and miR- 34a-5p (chr 1:9134225-9134425).</p></fn><fn id="TFN5"><label>d</label><p>rs12942666 is a SNP at 17q21.31 that was directly genotyped as part of COGs; it is in strong linkage disequilibrium (r<sup>2</sup>=0.99) with two other 17q21.31 SNPs that were directly genotyped but had less optimal clustering: rs2077606 (P=3.9 × 10<sup>−10</sup> for the serous subtype) and rs17631303 (P=4.7×10<sup>−10</sup> for the serous subtype).</p></fn><fn id="TFN6"><label>e</label><p>rs2960000 represents the most statistically significant SNP at 17q21.31 (among all invasives) that was imputed from the 1000 genome Project reference panel with an R-squared quality metric of 95% or greater (<ext-link ext-link-type="uri" xlink:href="http://www.1000genomes.org/page.php">http://www.1000genomes.org/page.php</ext-link>).</p></fn></table-wrap-foot></table-wrap></floats-group></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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