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

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Kelemen , L E , Earp , M , Fridley , B L , Chenevix-Trench , G , Fasching , P A , Beckmann , M W , Ekici , A B , Hein , A , Lambrechts , D , Lambrechts , S , Van Nieuwenhuysen , E , Vergote , I , Rossing , M A , Doherty , J A , Chang-Claude , J , Behrens , S , Moysich , K B , Cannioto , R , Lele , S , Odunsi , K , Goodman , M T , Shvetsov , Y B , Thompson , P J , Wilkens , L R , Doerk , T , Antonenkova , N , Bogdanova , N , Hillemanns , P , Runnebaum , I B , du Bois , A , Harter , P , Heitz , F , Schwaab , I , Butzow , R , Pelttari , L M , Nevanlinna , H , Modugno , F , Edwards , R P , Kelley , J L , Ness , R B , Karlan , B Y , Lester , J , Orsulic , S , Walsh , C , Kjaer , S K , Jensen , A , Cunningham , J M , Vierkant , R A , Giles , G G & Bruinsma , F 2018 , ' rs495139 in the TYMS-ENOSF1 Region and Risk of Ovarian Carcinoma of Mucinous Histology ' , International Journal of Molecular Sciences , vol. 19 , no. 9 , 2473 . https://doi.org/10.3390/ijms19092473

Title: rs495139 in the TYMS-ENOSF1 Region and Risk of Ovarian Carcinoma of Mucinous Histology
Author: Kelemen, Linda E.; Earp, Madalene; Fridley, Brooke L.; Chenevix-Trench, Georgia; Fasching, Peter A.; Beckmann, Matthias W.; Ekici, Arif B.; Hein, Alexander; Lambrechts, Diether; Lambrechts, Sandrina; Van Nieuwenhuysen, Els; Vergote, Ignace; Rossing, Mary Anne; Doherty, Jennifer A.; Chang-Claude, Jenny; Behrens, Sabine; Moysich, Kirsten B.; Cannioto, Rikki; Lele, Shashikant; Odunsi, Kunle; Goodman, Marc T.; Shvetsov, Yurii B.; Thompson, Pamela J.; Wilkens, Lynne R.; Doerk, Thilo; Antonenkova, Natalia; Bogdanova, Natalia; Hillemanns, Peter; Runnebaum, Ingo B.; du Bois, Andreas; Harter, Philipp; Heitz, Florian; Schwaab, Ira; Butzow, Ralf; Pelttari, Liisa M.; Nevanlinna, Heli; Modugno, Francesmary; Edwards, Robert P.; Kelley, Joseph L.; Ness, Roberta B.; Karlan, Beth Y.; Lester, Jenny; Orsulic, Sandra; Walsh, Christine; Kjaer, Susanne K.; Jensen, Allan; Cunningham, Julie M.; Vierkant, Robert A.; Giles, Graham G.; Bruinsma, Fiona
Contributor: University of Helsinki, Department of Pathology
University of Helsinki, Department of Obstetrics and Gynecology
University of Helsinki, Department of Obstetrics and Gynecology
Date: 2018-09
Language: eng
Number of pages: 13
Belongs to series: International Journal of Molecular Sciences
ISSN: 1422-0067
URI: http://hdl.handle.net/10138/272983
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 x 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.
Subject: consortia
enolase superfamily member 1
expression quantitative trait locus
genetics
gynecology
ovarian neoplasms
single-nucleotide polymorphism
thymidylate synthase
CANCER ASSOCIATION CONSORTIUM
CARBON TRANSFER PATHWAY
SYNTHASE MESSENGER-RNA
DIFFERENT HISTOTYPES
SUSCEPTIBILITY LOCI
CIGARETTE-SMOKING
GENETIC-VARIATION
METAANALYSIS
EXPRESSION
3122 Cancers
1182 Biochemistry, cell and molecular biology
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