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Int J Mol Sci. 2018 Aug 21;19(9). pii: E2473. doi: 10.3390/ijms19092473.

rs495139 in the TYMS-ENOSF1 Region and Risk of Ovarian Carcinoma of Mucinous Histology.

Kelemen LE1,2, Earp M3, Fridley BL4, Chenevix-Trench G5; Australian Ovarian Cancer Study Group6,7, Fasching PA8,9, Beckmann MW10, Ekici AB11, Hein A12, Lambrechts D13,14, Lambrechts S15, Van Nieuwenhuysen E16, Vergote I17, Rossing MA18,19, Doherty JA20, Chang-Claude J21,22, Behrens S23, Moysich KB24, Cannioto R25, Lele S26, Odunsi K27, Goodman MT28,29, Shvetsov YB30, Thompson PJ31,32, Wilkens LR33, Dörk T34, Antonenkova N35, Bogdanova N36, Hillemanns P37, Runnebaum IB38, du Bois A39,40, Harter P41,42, Heitz F43,44, Schwaab I45, Butzow R46,47, Pelttari LM48, Nevanlinna H49, Modugno F50,51,52, Edwards RP53, Kelley JL54, Ness RB55, Karlan BY56, Lester J57, Orsulic S58, Walsh C59, Kjaer SK60,61, Jensen A62, Cunningham JM63, Vierkant RA64, Giles GG65,66,67, Bruinsma F68, Southey MC69, Hildebrandt MAT70, Liang D71, Lu K72, Wu X73, Sellers TA74, Levine DA75, Schildkraut JM76, Iversen ES77, Terry KL78,79, Cramer DW80,81, Tworoger SS82,83, Poole EM84, Bandera EV85, Olson SH86, Orlow I87, Vestrheim Thomsen LC88,89, Bjorge L90,91, Krakstad C92,93, Tangen IL94,95, Kiemeney LA96, Aben KKH97,98, Massuger LFAG99, van Altena AM100, Pejovic T101,102, Bean Y103,104, Kellar M105,106, Cook LS107, Le ND108, Brooks-Wilson A109,110, Gronwald J111, Cybulski C112, Jakubowska A113,114, Lubiński J115, Wentzensen N116, Brinton LA117, Lissowska J118, Hogdall E119,120, Engelholm SA121, Hogdall C122, Lundvall L123, Nedergaard L124, Pharoah PDP125,126, Dicks E127, Song H128, Tyrer JP129, McNeish I130, Siddiqui N131, Carty K132, Glasspool R133, Paul J134, Campbell IG135,136,137, Eccles D138, Whittemore AS139, McGuire V140, Rothstein JH141,142, Sieh W143,144, Narod SA145, Phelan CM146, McLaughlin JR147, Risch HA148, Anton-Culver H149, Ziogas A150, Menon U151, Gayther SA152, Gentry-Maharaj A153, Ramus SJ154,155, Wu AH156, Pearce CL157,158, Lee AW159, Pike MC160,161, Kupryjanczyk J162, Podgorska A163, Plisiecka-Halasa J164, Sawicki W165, Goode EL166, Berchuck A167; Ovarian Cancer Association Consortium.

Author information

1
Hollings Cancer Center, Medical University of South Carolina, Charleston, SC 29425, USA. Kelemen@musc.edu.
2
Department of Public Health Sciences, College of Medicine, Medical University of South Carolina, Charleston, SC 29425, USA. Kelemen@musc.edu.
3
Department of Health Sciences Research, Division of Epidemiology, Mayo Clinic, Rochester, MN 55905, USA. madalene.earp@ucalgary.ca.
4
Department of Biostatistics and Bioinformatics, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612 USA. brooke.fridley@moffitt.org.
5
Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, QLD 4006, Australia. georgia.trench@qimr.edu.au.
6
Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, QLD 4006, Australia.
7
Peter MacCallum Cancer Centre, Melbourne, VIC 3000, Australia.
8
Department of Gynecology and Obstetrics, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Comprehensive Cancer Center, 91054 Erlangen, Germany. peter.fasching@uk-erlangen.de.
9
Department of Medicine, Division of Hematology and Oncology, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095, USA. peter.fasching@uk-erlangen.de.
10
Department of Gynecology and Obstetrics, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Comprehensive Cancer Center, 91054 Erlangen, Germany. fk-direktion@uk-erlangen.de.
11
Institute of Human Genetics, Friedrich-Alexander-University Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen Nuremberg, Erlangen 91054, Germany. arif.ekici@uk-erlangen.de.
12
Department of Gynecology and Obstetrics, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Comprehensive Cancer Center, 91054 Erlangen, Germany. alexander.hein@uk-erlangen.de.
13
Vesalius Research Center, University of Leuven, Leuven 3001, Belgium. diether.lambrechts@vib-kuleuven.be.
14
Laboratory for Translational Genetics, Department of Oncology, University of Leuven, Leuven 3000, Belgium. diether.lambrechts@vib-kuleuven.be.
15
Division of Gynecologic Oncology, Department of Obstetrics and Gynaecology and Leuven Cancer Institute, University Hospitals Leuven, Leuven 3000, Belgium. sandrina.lambrechts@mumc.nl.
16
Division of Gynecologic Oncology, Department of Obstetrics and Gynaecology and Leuven Cancer Institute, University Hospitals Leuven, Leuven 3000, Belgium. els.vannieuwenhuysen@uzleuven.be.
17
Division of Gynecologic Oncology, Department of Obstetrics and Gynaecology and Leuven Cancer Institute, University Hospitals Leuven, Leuven 3000, Belgium. ignace.vergote@uzleuven.be.
18
Program in Epidemiology, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA. mrossing@fhcrc.org.
19
Department of Epidemiology, University of Washington, Seattle, WA 98402, USA. mrossing@fhcrc.org.
20
Huntsman Cancer Institute, Department of Population Health Sciences, University of Utah, Salt Lake City, UT 84112, USA. jennifer.doherty@hci.utah.edu.
21
Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg 69120, Germany. j.chang-claude@dkfz-heidelberg.de.
22
University Cancer Center Hamburg (UCCH), University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany. j.chang-claude@dkfz-heidelberg.de.
23
Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg 69120, Germany. s.behrens@dkfz.de.
24
Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, NY 14263, USA. moysich@roswellpark.org.
25
Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, NY 14263, USA. rikki.cannioto@roswellpark.org.
26
Department of Gynecological Oncology, Roswell Park Cancer Institute, Buffalo, NY 14263, USA. shashi.lele@roswellpark.org.
27
Department of Gynecological Oncology, Roswell Park Cancer Institute, Buffalo, NY 14263, USA. kunle.odunsi@roswellpark.org.
28
Department of Cancer Prevention and Control, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA. marc.goodman@cshs.org.
29
Community and Population Health Research Institute, Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA. marc.goodman@cshs.org.
30
Cancer Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI 96813, USA. yshvetso@cc.hawaii.edu.
31
Department of Cancer Prevention and Control, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA. pamela.thompson@cshs.org.
32
Community and Population Health Research Institute, Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA. pamela.thompson@cshs.org.
33
Cancer Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI 96813, USA. lynne@cc.hawaii.edu.
34
Gynaecology Research Unit, Hannover Medical School, Hannover 30625, Germany. doerk.thilo@mh-hannover.de.
35
Byelorussian Institute for Oncology and Medical Radiology Aleksandrov N.N., Minsk 223040, Belarus. antonenkova.natalia.omd@tut.by.
36
Gynaecology Research Unit, Hannover Medical School, Hannover 30625, Germany. bogdanova.natalia@mh-hannover.de.
37
Clinics of Obstetrics and Gynaecology, Hannover Medical School, Hannover 30625, Germany. hillemanns.peter@mh-hannover.de.
38
Department of Gynecology, Jena University Hospital-Friedrich Schiller University, Jena 07743, Germany. ingo.runnebaum@med.uni-jena.de.
39
Department of Gynecology and Gynecologic Oncology, Kliniken Essen-Mitte (KEM), Essen 45136, Germany. prof.dubois@googlemail.com.
40
Department of Gynecology and Gynecologic Oncology, Dr. Horst Schmidt Kliniken Wiesbaden, Wiesbaden 65199, Germany. prof.dubois@googlemail.com.
41
Department of Gynecology and Gynecologic Oncology, Kliniken Essen-Mitte (KEM), Essen 45136, Germany. p.harter@gmx.de.
42
Department of Gynecology and Gynecologic Oncology, Dr. Horst Schmidt Kliniken Wiesbaden, Wiesbaden 65199, Germany. p.harter@gmx.de.
43
Department of Gynecology and Gynecologic Oncology, Kliniken Essen-Mitte (KEM), Essen 45136, Germany. florian.heitz@gmx.net.
44
Department of Gynecology and Gynecologic Oncology, Dr. Horst Schmidt Kliniken Wiesbaden, Wiesbaden 65199, Germany. florian.heitz@gmx.net.
45
Praxis für Humangenetik, Wiesbaden 65187, Germany. iraschwaab@gmx.de.
46
Department of Pathology, University of Helsinki and Helsinki University Hospital, Helsinki 00290, Finland. ralf.butzow@hus.fi.
47
Department of Obstetrics and Gynecology, University of Helsinki and Helsinki University Hospital, Helsinki 00290, Finland. ralf.butzow@hus.fi.
48
Department of Obstetrics and Gynecology, University of Helsinki and Helsinki University Hospital, Helsinki 00290, Finland. liisa.pelttari@helsinki.fi.
49
Department of Obstetrics and Gynecology, University of Helsinki and Helsinki University Hospital, Helsinki 00290, Finland. heli.nevanlinna@hus.fi.
50
Division of Gynecologic Oncology, Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA. fm@cs.cmu.edu.
51
Department of Epidemiology, University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA 15213, USA. fm@cs.cmu.edu.
52
Women's Cancer Research Program, Magee-Women's Research Institute and Hillman Cancer Center, Pittsburgh, PA 15213, USA. fm@cs.cmu.edu.
53
Division of Gynecologic Oncology, Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA. redwards@mail.magee.edu.
54
Division of Gynecologic Oncology, Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA. jkelley@mail.magee.edu.
55
School of Public Health, The University of Texas Health Science Center at Houston (UTHealth), Houston, TX 77030, USA. roberta.b.ness@uth.tmc.edu.
56
Women's Cancer Program at the Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA. beth.karlan@cshs.org.
57
Women's Cancer Program at the Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA. jenny.lester@cshs.org.
58
Women's Cancer Program at the Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA. sandra.orsulic@cshs.org.
59
Women's Cancer Program at the Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA. christine.walsh@cshs.org.
60
Department of Gynaecology, Rigshospitalet, University of Copenhagen, DK-2100 Copenhagen, Denmark. susanne@cancer.dk.
61
Department of Virus, Lifestyle and Genes, Danish Cancer Society Research Centre, DK-2100 Copenhagen, Denmark. susanne@cancer.dk.
62
Department of Virus, Lifestyle and Genes, Danish Cancer Society Research Centre, DK-2100 Copenhagen, Denmark. allan@cancer.dk.
63
Department of Laboratory Medicine and Pathology, Division of Experimental Pathology, Mayo Clinic, Rochester, MN 55905, USA. cunningham.julie@mayo.edu.
64
Department of Health Sciences Research, Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN 55905, USA. vierkant.robert@mayo.edu.
65
Centre for Epidemiology and Biostatistics, University of Melbourne, VIC 3010, Australia. graham.giles@cancervic.org.au.
66
Cancer Epidemiology and Intelligence Division, Cancer Council Victoria, Melbourne, VIC 3004, Australia. graham.giles@cancervic.org.au.
67
Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, VIC 3800, Australia. graham.giles@cancervic.org.au.
68
Cancer Epidemiology and Intelligence Division, Cancer Council Victoria, Melbourne, VIC 3004, Australia. fiona.bruinsma@cancervic.org.au.
69
Department of Pathology, University of Melbourne, Melbourne, VIC 3010, Australia. msouthey@unimelb.edu.au.
70
Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. mhildebr@mdanderson.org.
71
College of Pharmacy and Health Sciences, Texas Southern University, Houston, TX 77004, USA. liang_dx@tsu.edu.
72
Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. khlu@mdanderson.org.
73
Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. xwu@mdanderson.org.
74
Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA. thomas.sellers@moffitt.org.
75
Laura and Isaac Perlmutter Cancer Center, New York University Langone Health, New York, NY 10016, USA. Douglas.Levine@nyumc.org.
76
Department of Public Health Sciences, University of Virginia, Charlottesville, VA 22908, USA. jms2yf@virginia.edu.
77
Department of Statistical Science, Duke University, Durham, NC 27708, USA. iversen@stat.duke.edu.
78
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA. kterry@partners.org.
79
Obstetrics and Gynecology Epidemiology Center, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA. kterry@partners.org.
80
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA. dcramer@partners.org.
81
Obstetrics and Gynecology Epidemiology Center, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA. dcramer@partners.org.
82
Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA. shelley.tworoger@moffitt.org.
83
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA. shelley.tworoger@moffitt.org.
84
Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA. nhlip@channing.harvard.edu.
85
Cancer Prevention and Control Program, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ 08903, USA. banderel@cinj.rutgers.edu.
86
Memorial Sloan Kettering Cancer Center, Department of Epidemiology and Biostatistics, New York, NY 10065, USA. olsons@mskcc.org.
87
Memorial Sloan Kettering Cancer Center, Department of Epidemiology and Biostatistics, New York, NY 10065, USA. orlowi@mskcc.org.
88
Department of Gynecology and Obstetrics, Haukeland University Hospital, Bergen 5021, Norway. Liv.Vestrheim@uib.no.
89
Centre for Cancer Biomarkers CCBIO, Department of Clinical Science, University of Bergen, Bergen 5020, Norway. Liv.Vestrheim@uib.no.
90
Department of Gynecology and Obstetrics, Haukeland University Hospital, Bergen 5021, Norway. line.bjorge@uib.no.
91
Centre for Cancer Biomarkers CCBIO, Department of Clinical Science, University of Bergen, Bergen 5020, Norway. line.bjorge@uib.no.
92
Department of Gynecology and Obstetrics, Haukeland University Hospital, Bergen 5021, Norway. camilla.krakstad@k2.uib.no.
93
Centre for Cancer Biomarkers CCBIO, Department of Clinical Science, University of Bergen, Bergen 5020, Norway. camilla.krakstad@k2.uib.no.
94
Department of Gynecology and Obstetrics, Haukeland University Hospital, Bergen 5021, Norway. ingvild.tangen@k2.uib.no.
95
Centre for Cancer Biomarkers CCBIO, Department of Clinical Science, University of Bergen, Bergen 5020, Norway. ingvild.tangen@k2.uib.no.
96
Radboud University Medical Centre, Radboud Institute for Health Sciences, Nijmegen 6525 EZ, The Netherlands. bart.kiemeney@radboudumc.nl.
97
Radboud University Medical Centre, Radboud Institute for Health Sciences, Nijmegen 6525 EZ, The Netherlands. k.aben@iknl.nl.
98
Netherlands Comprehensive Cancer Organisation, Utrecht 3511 DT, The Netherlands. k.aben@iknl.nl.
99
Radboud University Medical Centre, Department of Obstetrics and Gynecology, Nijmegen 6525 GA, The Netherlands. leon.massuger@radboudumc.nl.
100
Radboud University Medical Centre, Department of Obstetrics and Gynecology, Nijmegen 6525 GA, The Netherlands. anne.vanaltena@radboudumc.nl.
101
Department of Obstetrics and Gynecology, Oregon Health and Science University, Portland, OR 97239, USA. pejovict@ohsu.edu.
102
Knight Cancer Institute, Oregon Health and Science University, Portland, OR 97239, USA. pejovict@ohsu.edu.
103
Department of Obstetrics and Gynecology, Oregon Health and Science University, Portland, OR 97239, USA. beany@ohsu.edu.
104
Knight Cancer Institute, Oregon Health and Science University, Portland, OR 97239, USA. beany@ohsu.edu.
105
Department of Obstetrics and Gynecology, Oregon Health and Science University, Portland, OR 97239, USA. kellar@ohsu.edu.
106
Knight Cancer Institute, Oregon Health and Science University, Portland, OR 97239, USA. kellar@ohsu.edu.
107
Division of Epidemiology, Biostatistics and Preventive Medicine, Department of Internal Medicine, University of New Mexico, Albuquerque, NM 87131, USA. lcook@salud.unm.edu.
108
Cancer Control Research, British Columbia Cancer Agency, Vancouver, BC V5Z 1L3, Canada. nle@bccrc.ca.
109
Canada's Michael Smith Genome Sciences Centre, British Columbia Cancer Agency, Vancouver, BC V5Z 1L3, Canada. abrooks-wilson@bcgsc.ca.
110
Department of Biomedical Physiology and Kinesiology, Simon Fraser University, Burnaby, BC V5A 1S6, Canada. abrooks-wilson@bcgsc.ca.
111
International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University, Szczecin 71-252, Poland. jgron@sci.pam.szczecin.pl.
112
International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University, Szczecin 71-252, Poland. cezarycy@sci.pam.szczecin.pl.
113
International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University, Szczecin 71-252, Poland. aniaj@sci.pam.szczecin.pl.
114
Independent Laboratory of Molecular Biology and Genetic Diagnostics, Pomeranian Medical University, Szczecin 70-111, Poland. aniaj@sci.pam.szczecin.pl.
115
International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University, Szczecin 71-252, Poland. lubinski@pum.edu.pl.
116
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892, USA. wentzenn@mail.nih.gov.
117
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892, USA. brintonl@mail.nih.gov.
118
Department of Cancer Epidemiology and Prevention, M. Sklodowska-Curie Institute-Oncology Center, Warsaw 02-034, Poland. lissowsj@coi.waw.pl.
119
Department of Virus, Lifestyle and Genes, Danish Cancer Society Research Centre, DK-2100 Copenhagen, Denmark. hogdall@dadlnet.dk.
120
Department of Pathology, Herlev Hospital, University of Copenhagen, Copenhagen DK-2100, Denmark. hogdall@dadlnet.dk.
121
Department of Radiation Oncology, Rigshospitalet, University of Copenhagen, Copenhagen DK-2100, Denmark. svend.aage.engelholm@rh.regionh.dk.
122
Department of Gynaecology, Rigshospitalet, University of Copenhagen, DK-2100 Copenhagen, Denmark. claus.hogdall@regionh.dk.
123
Department of Gynaecology, Rigshospitalet, University of Copenhagen, DK-2100 Copenhagen, Denmark. lene.lundvall@regionh.dk.
124
Department of Pathology, Rigshospitalet, University of Copenhagen, Copenhagen DK-2100, Denmark. lotte.thomsen.01@regionh.dk.
125
The Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge CB1 8RN, UK. pp10001@medschl.cam.ac.uk.
126
The Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge CB1 8RN, UK. pp10001@medschl.cam.ac.uk.
127
The Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge CB1 8RN, UK. emd43@medschl.cam.ac.uk.
128
The Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge CB1 8RN, UK. hs310@medschl.cam.ac.uk.
129
The Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge CB1 8RN, UK. jpt34@medschl.cam.ac.uk.
130
Ovarian Cancer Action Research Centre, Department of Surgery and Cancer, Imperial College London, London W12 0NN, UK. i.mcneish@imperial.ac.uk.
131
Department of Gynaecological Oncology, Glasgow Royal Infirmary, Glasgow G4 0SF, UK. nadeem.siddiqui@ggc.scot.nhs.uk.
132
Cancer Research UK Clinical Trials Unit, The Beatson West of Scotland Cancer Centre, Glasgow G12 0YN, UK. karen.carty@glasgow.ac.uk.
133
Cancer Research UK Clinical Trials Unit, The Beatson West of Scotland Cancer Centre, Glasgow G12 0YN, UK. ros.glasspool@ggc.scot.nhs.uk.
134
Cancer Research UK Clinical Trials Unit, The Beatson West of Scotland Cancer Centre, Glasgow G12 0YN, UK. james.paul@glasgow.ac.uk.
135
Department of Pathology, University of Melbourne, Melbourne, VIC 3010, Australia. ian.campbell@petermac.org.
136
Cancer Genetics Laboratory, Research Division, Peter MacCallum Cancer Centre, St Andrews Place, East Melbourne, VIC 3000, Australia. ian.campbell@petermac.org.
137
Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, VIC 3000, Australia. ian.campbell@petermac.org.
138
Faculty of Medicine, University of Southampton, Southampton SO17 1BJ, UK. d.m.eccles@soton.ac.uk.
139
Department of Health Research and Policy, Stanford University School of Medicine, Stanford, CA 94305, USA. alicesw@stanford.edu.
140
Department of Health Research and Policy, Stanford University School of Medicine, Stanford, CA 94305, USA. vmcguire@stanford.edu.
141
Department of Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. joseph.rothstein@mssm.edu.
142
Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. joseph.rothstein@mssm.edu.
143
Department of Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. weiva.sieh@mssm.edu.
144
Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. weiva.sieh@mssm.edu.
145
Women's College Research Institute, University of Toronto, Toronto, ON M5S 1A8, Canada. steven.narod@wchospital.ca.
146
Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA. ocacdata@duke.edu.
147
Public Health Ontario, Samuel Lunenfeld Research Institute, Toronto, ON M5T 3L9, Canada. jmclaugh@lunenfeld.ca.
148
Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, CT 06510, USA. harvey.risch@yale.edu.
149
Department of Epidemiology, Genetic Epidemiology Research Institute, School of Medicine, University of California Irvine, Irvine, CA 92617, USA. hantoncu@uci.edu.
150
Department of Epidemiology, Genetic Epidemiology Research Institute, School of Medicine, University of California Irvine, Irvine, CA 92617, USA. aziogas@uci.edu.
151
MRC Clinical Trials at UCL, Institute of Clinical Trials & Methodology, Population Health Sciences, University College London, London, WC1V 6LJ, UK. u.menon@ucl.ac.uk.
152
Department of Biomedical Sciences and Center for Cancer Prevention and Translational Genomics, Samuel Oschin Comprensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA. simon.gayther@cshs.org.
153
MRC Clinical Trials at UCL, Institute of Clinical Trials & Methodology, Population Health Sciences, University College London, London, WC1V 6LJ, UK. a.gentry-maharaj@ucl.ac.uk.
154
School of Women's and Children's Health, Faculty of Medicine, University of New South Wales, Sydney, NSW 2052, Australia. s.ramus@unsw.edu.au.
155
The Kinghorn Cancer Centre, Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, NSW 2010, Australia. s.ramus@unsw.edu.au.
156
Department of Preventive Medicine, Keck School of Medicine, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA 90033, USA. anna.wu@med.usc.edu.
157
Department of Preventive Medicine, Keck School of Medicine, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA 90033, USA. lpearce@umich.edu.
158
Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI 48109, USA. lpearce@umich.edu.
159
Department of Public Health, California State University, Fullerton, CA 92831, USA. alicelee@fullerton.edu.
160
Memorial Sloan Kettering Cancer Center, Department of Epidemiology and Biostatistics, New York, NY 10065, USA. pikem@mskcc.org.
161
Department of Preventive Medicine, Keck School of Medicine, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA 90033, USA. pikem@mskcc.org.
162
Department of Pathology and Laboratory Diagnostics, Maria Sklodowska-Curie Institute-Oncology Center, Warsaw 02-034, Poland. jkupry@coi.waw.pl.
163
Department of Pathology and Laboratory Diagnostics, Maria Sklodowska-Curie Institute-Oncology Center, Warsaw 02-034, Poland. ag.podgorski@yahoo.de.
164
Department of Pathology and Laboratory Diagnostics, Maria Sklodowska-Curie Institute-Oncology Center, Warsaw 02-034, Poland. jopliha@coi.waw.pl.
165
Department of Obstetrics, Gynecology and Oncology, Second Faculty of Medicine, Medical University of Warsaw, Mazovian Bródno Hospital, Warsaw 03-242, Poland. saw55@wp.pl.
166
Department of Health Sciences Research, Division of Epidemiology, Mayo Clinic, Rochester, MN 55905, USA. egoode@mayo.edu.
167
Department of Obstetrics and Gynecology, Duke University Medical Center, Durham, NC 27710, USA. andrew.berchuck@duke.edu.

Abstract

Thymidylate synthase (TYMS) is a crucial enzyme for DNA synthesis. TYMS expression is regulated by its antisense mRNA, ENOSF1. Disrupted regulation may promote uncontrolled DNA synthesis and tumor growth. We sought to replicate our previously reported association between rs495139 in the TYMS-ENOSF1 3' gene region and increased risk of mucinous ovarian carcinoma (MOC) in an independent sample. Genotypes from 24,351 controls to 15,000 women with invasive OC, including 665 MOC, were available. We estimated per-allele odds ratios (OR) and 95% confidence intervals (CI) using unconditional logistic regression, and meta-analysis when combining these data with our previous report. The association between rs495139 and MOC was not significant in the independent sample (OR = 1.09; 95% CI = 0.97⁻1.22; p = 0.15; N = 665 cases). Meta-analysis suggested a weak association (OR = 1.13; 95% CI = 1.03⁻1.24; p = 0.01; N = 1019 cases). No significant association with risk of other OC histologic types was observed (p = 0.05 for tumor heterogeneity). In expression quantitative trait locus (eQTL) analysis, the rs495139 allele was positively associated with ENOSF1 mRNA expression in normal tissues of the gastrointestinal system, particularly esophageal mucosa (r = 0.51, p = 1.7 × 10-28), and nonsignificantly in five MOC tumors. The association results, along with inconclusive tumor eQTL findings, suggest that a true effect of rs495139 might be small.

KEYWORDS:

consortia; enolase superfamily member 1; expression quantitative trait locus; genetics; gynecology; ovarian neoplasms; single-nucleotide polymorphism; thymidylate synthase

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