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

Kelemen LE, Earp M, Fridley BL, Chenevix-Trench G, Fasching P, 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 (2018)

Publication Type: Journal article

Publication year: 2018

Journal

Book Volume: 19

Journal Issue: 9

DOI: 10.3390/ijms19092473

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.

Authors with CRIS profile

Involved external institutions

Medical University of South Carolina (MUSC) United States (USA) (US) Mayo Clinic United States (USA) (US) H. Lee Moffitt Cancer Center & Research Institute United States (USA) (US) QIMR Berghofer Medical Research Institute (früher: the Queensland Institute of Medical Research) Australia (AU) Katholieke Universiteit Leuven (KUL) / Catholic University of Leuven Belgium (BE) University Hospital Leuven (UZ) / Universitaire ziekenhuizen Leuven Belgium (BE) Fred Hutchinson Cancer Research Center Canada (CA) University of Utah United States (USA) (US) Deutsches Krebsforschungszentrum (DKFZ) Germany (DE) Roswell Park Cancer Institute United States (USA) (US) Cedars-Sinai Medical Center United States (USA) (US) University of Hawaii (U.H.) United States (USA) (US) Medizinische Hochschule Hannover (MHH) / Hannover Medical School Germany (DE) N.N. Alexandrov National Cancer Centre of Belarus for Oncology and Medical Radiology Belarus (BY) Friedrich-Schiller-Universität Jena Germany (DE) Kliniken Essen-Mitte Germany (DE) Helsingin yliopisto / University of Helsinki Finland (FI) Helsinki University Central Hospital (HUCH) / Helsingin seudun yliopistollinen keskussairaala (HYKS) Finland (FI) University of Pittsburgh United States (USA) (US) University of Texas Health Science Center at Houston (UTHealth) United States (USA) (US) University of Copenhagen Denmark (DK) Danish Cancer Society Denmark (DK) Cancer Council Victoria Australia (AU) The University of Melbourne Australia (AU) University of Texas MD Anderson Cancer Center United States (USA) (US) Texas Southern University (TSU) United States (USA) (US) NYU Langone Medical Center United States (USA) (US) University of Virginia (UVA) United States (USA) (US) Duke University United States (USA) (US) Harvard University United States (USA) (US) Rutgers Cancer Institute of New Jersey United States (USA) (US) Memorial Sloan Kettering Cancer Center United States (USA) (US) Haukeland University Hospital / Haukeland universitetssykehus Norway (NO) Radboud University Nijmegen Netherlands (NL) Oregon Health and Science University (OSHU) United States (USA) (US) University of New Mexico (UNM) / Universidad de Nuevo México United States (USA) (US) University of Cambridge United Kingdom (GB) Beatson West of Scotland Cancer Centre (BWSCC) United Kingdom (GB) University of New South Wales (UNSW) Australia (AU) California State University (CSUF) United States (USA) (US) British Columbia Cancer Agency Canada (CA) Pomeranian Medical University / Pomorski Uniwersytet Medyczny w Szczecinie (PMU) Poland (PL) National Cancer Institute (NCI) United States (USA) (US) Maria Skłodowska-Curie Institute of Oncology / Centrum Onkologii–Instytut im. Marii Skłodowskiej-Curie w Warszawie Poland (PL) Imperial College London / The Imperial College of Science, Technology and Medicine United Kingdom (GB) Glasgow Royal Infirmary (GRI) United Kingdom (GB) University of Southampton United Kingdom (GB) Stanford University United States (USA) (US) Icahn School of Medicine at Mount Sinai United States (USA) (US) University of Toronto Canada (CA) Sinai Health System Canada (CA) Yale University United States (USA) (US) University of California Irvine United States (USA) (US) University College London (UCL) United Kingdom (GB) University of Southern California (USC) United States (USA) (US) Wrocław Medical University / Uniwersytet Medyczny we Wrocławiu Poland (PL)

How to cite

APA:

Kelemen, L.E., Earp, M., Fridley, B.L., Chenevix-Trench, G., Fasching, P., 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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