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

Journal article


Publication Details

Author(s): Kelemen LE, Earp M, Fridley BL, Chenevix-Trench G, Fasching PA, Beckmann M, Ekici AB, Hein A, Lambrechts D, Lambrechts S, Van Nieuwenhuysen E, Vergote I, Rossing MA, Doherty JA, Chang-Claude J, Behrens S, Moysich KB, Cannioto R, Lele S, Odunsi K, Goodman MT, Shvetsov YB, Thompson PJ, Wilkens LR, Doerk T, Antonenkova N, Bogdanova N, Hillemanns P, Runnebaum IB, Du Bois A, Harter P, Heitz F, Schwaab I, Butzow R, Pelttari LM, Nevanlinna H, Modugno F, Edwards RP, Kelley JL, Ness RB, Karlan BY, Lester J, Orsulic S, Walsh C, Kjaer SK, Jensen A, Cunningham JM, Vierkant RA, Giles GG, Bruinsma F, Southey MC, Hildebrandt MAT, Liang D, Lu K, Wu X, Sellers TA, Levine DA, Schildkraut JM, Iversen ES, Terry KL, Cramer DW, Tworoger SS, Poole EM, Bandera EV, Olson SH, Orlow I, Thomsen LCV, Bjorge L, Krakstad C, Tangen IL, Kiemeney LA, Aben KKH, Massuger LFAG, Van Altena AM, Pejovic T, Bean Y, Kellar M, Cook LS, Le ND, Brooks-Wilson A, Gronwald J, Cybulski C, Jakubowska A, Lubinski J, Wentzensen N, Brinton LA, Lissowska J, Hogdall E, Engelholm SA, Hogdall C, Lundvall L, Nedergaard L, Pharoah PDP, Dicks E, Song H, Tyrer JP, Mcneish I, Siddiqui N, Carty K, Glasspool R, Paul J, Campbell IG, Eccles D, Whittemore AS, Mcguire V, Rothstein JH, Sieh W, Narod SA, Phelan CM, Mclaughlin JR, Risch HA, Anton-Culver H, Ziogas A, Menon U, Gayther SA, Gentry-Maharaj A, Ramus SJ, Wu AH, Pearce CL, Lee AW, Pike MC, Kupryjanczyk J, Podgorska A, Plisiecka-Halasa J, Sawicki W, Goode EL, Berchuck A
Journal: International Journal of Molecular Sciences
Publication year: 2018
Volume: 19
Journal issue: 9
ISSN: 1422-0067


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.


FAU Authors / FAU Editors

Beckmann, Matthias Prof. Dr.
Lehrstuhl für Geburtshilfe und Frauenheilkunde
Fasching, Peter PD Dr.
Professur für Translationale Frauenheilkunde und Geburtshilfe
Hein, Alexander PD Dr.
Frauenklinik


External institutions
Beatson West of Scotland Cancer Centre (BWSCC)
British Columbia Cancer Agency
California State University (CSUF)
Cancer Council Victoria
Cedars-Sinai Medical Center
Danish Cancer Society
Deutsches Krebsforschungszentrum (DKFZ)
Duke University
Fred Hutchinson Cancer Research Center
Friedrich-Schiller-Universität Jena
Glasgow Royal Infirmary (GRI)
Hannover Medical School / Medizinische Hochschule Hannover (MHH)
Harvard University
Haukeland University Hospital / Haukeland universitetssykehus
Helsingin yliopisto / University of Helsinki
Helsinki University Central Hospital (HUCH) / Helsingin seudun yliopistollinen keskussairaala (HYKS)
H. Lee Moffitt Cancer Center & Research Institute
Icahn School of Medicine at Mount Sinai
Imperial College London / The Imperial College of Science, Technology and Medicine
Katholieke Universiteit Leuven (KUL) / Catholic University of Leuven
Kliniken Essen-Mitte
Maria Skłodowska-Curie Institute of Oncology / Centrum Onkologii–Instytut im. Marii Skłodowskiej-Curie w Warszawie
Mayo Clinic
Medical University of South Carolina (MUSC)
Memorial Sloan Kettering Cancer Center
National Cancer Institute (NCI)
N.N. Alexandrov National Cancer Centre of Belarus for Oncology and Medical Radiology
NYU Langone Medical Center
Oregon Health and Science University (OSHU)
Pomeranian Medical University / Pomorski Uniwersytet Medyczny w Szczecinie (PMU)
QIMR Berghofer Medical Research Institute (früher: the Queensland Institute of Medical Research)
Radboud University Nijmegen
Roswell Park Cancer Institute
Rutgers Cancer Institute of New Jersey
Sinai Health System
Stanford University
Texas Southern University (TSU)
The University of Melbourne
University College London (UCL) (University of London)
University Hospital Leuven (UZ) / Universitaire ziekenhuizen Leuven
University of California Irvine
University of Cambridge
University of Copenhagen
University of Hawaii (U.H.)
University of New Mexico
University of New South Wales (UNSW)
University of Pittsburgh
University of Southampton
University of Southern California (USC)
University of Texas Health Science Center at Houston (UTHealth)
University of Texas MD Anderson Cancer Center
University of Toronto
University of Utah
University of Virginia (UVA)
Wrocław Medical University / Uniwersytet Medyczny we Wrocławiu


How to cite

APA:
Kelemen, L.E., Earp, M., Fridley, B.L., Chenevix-Trench, G., Fasching, P.A., Beckmann, M.,... Berchuck, A. (2018). rs495139 in the TYMS-ENOSF1 Region and Risk of Ovarian Carcinoma of Mucinous Histology. International Journal of Molecular Sciences, 19(9). https://dx.doi.org/10.3390/ijms19092473

MLA:
Kelemen, Linda E., et al. "rs495139 in the TYMS-ENOSF1 Region and Risk of Ovarian Carcinoma of Mucinous Histology." International Journal of Molecular Sciences 19.9 (2018).

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Last updated on 2019-22-01 at 21:08