rs495139 in the TYMS-ENOSF1 region and risk of ovarian carcinoma of mucinous histology

Australian Ovarian Cancer Study Group; Ovarian Cancer Association Consortium

doi:10.3390/ijms19092473

rs495139 in the TYMS-ENOSF1 region and risk of ovarian carcinoma of mucinous histology

Australian Ovarian Cancer Study Group
, Ovarian Cancer Association Consortium

Department of Epidemiology and Environmental Health

Department of Genetics and Computational Biology
Queensland Institute of Medical Research
Peter Maccallum Cancer Centre
Medical University of South Carolina
Mayo Clinic Rochester, MN
Moffitt Cancer Center
Friedrich-Alexander University Erlangen-Nürnberg
University of California at Los Angeles
KU Leuven
Fred Hutchinson Cancer Research Center
University of Washington
University of Utah
German Cancer Research Center
University of Hamburg
Roswell Park Cancer Institute
Cedars-Sinai Medical Center
University of Hawai'i at Mānoa
Hannover Medical School
Byelorussian Institute for Oncology and Medical Radiology Aleksandrov N.N.
Friedrich Schiller University Jena
Kliniken Essen-Mitte
Dr. Horst Schmidt Klinik GmbH
Praxis für Humangenetik
Helsinki University Hospital
University of Pittsburgh
University of Texas Health Science Center at Houston
University of Copenhagen
Danish Cancer Society
University of Melbourne
Cancer Council Victoria
Monash University

Research output: Contribution to journal › Article › peer-review

3 Scopus citations

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.

Original language	English
Article number	2473
Journal	International Journal of Molecular Sciences
Volume	19
Issue number	9
DOIs	https://doi.org/10.3390/ijms19092473
State	Published - Sep 2018

Keywords

Consortia
Enolase superfamily member 1
Expression quantitative trait locus
Genetics
Gynecology
Ovarian neoplasms
Single-nucleotide polymorphism
Thymidylate synthase

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10.3390/ijms19092473

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@article{09b5f78b64f546f0830a8a3e4a388026,

title = "rs495139 in the TYMS-ENOSF1 region and risk of ovarian carcinoma of mucinous histology",

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",

author = "\{Australian Ovarian Cancer Study Group\} and \{Ovarian Cancer Association Consortium\} and Kelemen, \{Linda E.\} and Madalene Earp and Fridley, \{Brooke L.\} and Georgia Chenevix-Trench and Fasching, \{Peter A.\} and Beckmann, \{Matthias W.\} and Ekici, \{Arif B.\} and Alexander Hein and Diether Lambrechts and Sandrina Lambrechts and \{Van Nieuwenhuysen\}, Els and Ignace Vergote and Rossing, \{Mary Anne\} and Doherty, \{Jennifer A.\} and Jenny Chang-Claude and Sabine Behrens and Moysich, \{Kirsten B.\} and Rikki Cannioto and Shashikant Lele and Kunle Odunsi and Goodman, \{Marc T.\} and Shvetsov, \{Yurii B.\} and Thompson, \{Pamela J.\} and Wilkens, \{Lynne R.\} and Thilo D{\"o}rk and Natalia Antonenkova and Natalia Bogdanova and Peter Hillemanns and Runnebaum, \{Ingo B.\} and Bois, \{Andreas Du\} and Philipp Harter and Florian Heitz and Ira Schwaab and Ralf Butzow and Pelttari, \{Liisa M.\} and Heli Nevanlinna and Francesmary Modugno and Edwards, \{Robert P.\} and Kelley, \{Joseph L.\} and Ness, \{Roberta B.\} and Karlan, \{Beth Y.\} and Jenny Lester and Sandra Orsulic and Christine Walsh and Kjaer, \{Susanne K.\} and Allan Jensen and Cunningham, \{Julie M.\} and Vierkant, \{Robert A.\} and Giles, \{Graham G.\} and Fiona Bruinsma",

note = "Publisher Copyright: {\textcopyright} 2018 by the authors. Licensee MDPI, Basel, Switzerland.",

year = "2018",

month = sep,

doi = "10.3390/ijms19092473",

language = "English",

volume = "19",

journal = "International Journal of Molecular Sciences",

issn = "1661-6596",

publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",

number = "9",

}

TY - JOUR

T1 - rs495139 in the TYMS-ENOSF1 region and risk of ovarian carcinoma of mucinous histology

AU - Australian Ovarian Cancer Study Group

AU - Ovarian Cancer Association Consortium

AU - Kelemen, Linda E.

AU - Earp, Madalene

AU - Fridley, Brooke L.

AU - Chenevix-Trench, Georgia

AU - Fasching, Peter A.

AU - Beckmann, Matthias W.

AU - Ekici, Arif B.

AU - Hein, Alexander

AU - Lambrechts, Diether

AU - Lambrechts, Sandrina

AU - Van Nieuwenhuysen, Els

AU - Vergote, Ignace

AU - Rossing, Mary Anne

AU - Doherty, Jennifer A.

AU - Chang-Claude, Jenny

AU - Behrens, Sabine

AU - Moysich, Kirsten B.

AU - Cannioto, Rikki

AU - Lele, Shashikant

AU - Odunsi, Kunle

AU - Goodman, Marc T.

AU - Shvetsov, Yurii B.

AU - Thompson, Pamela J.

AU - Wilkens, Lynne R.

AU - Dörk, Thilo

AU - Antonenkova, Natalia

AU - Bogdanova, Natalia

AU - Hillemanns, Peter

AU - Runnebaum, Ingo B.

AU - Bois, Andreas Du

AU - Harter, Philipp

AU - Heitz, Florian

AU - Schwaab, Ira

AU - Butzow, Ralf

AU - Pelttari, Liisa M.

AU - Nevanlinna, Heli

AU - Modugno, Francesmary

AU - Edwards, Robert P.

AU - Kelley, Joseph L.

AU - Ness, Roberta B.

AU - Karlan, Beth Y.

AU - Lester, Jenny

AU - Orsulic, Sandra

AU - Walsh, Christine

AU - Kjaer, Susanne K.

AU - Jensen, Allan

AU - Cunningham, Julie M.

AU - Vierkant, Robert A.

AU - Giles, Graham G.

AU - Bruinsma, Fiona

PY - 2018/9

Y1 - 2018/9

N2 - 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.

AB - 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.

KW - Consortia

KW - Enolase superfamily member 1

KW - Expression quantitative trait locus

KW - Genetics

KW - Gynecology

KW - Ovarian neoplasms

KW - Single-nucleotide polymorphism

KW - Thymidylate synthase

UR - https://www.scopus.com/pages/publications/85052837195

U2 - 10.3390/ijms19092473

DO - 10.3390/ijms19092473

M3 - Article

C2 - 30134598

AN - SCOPUS:85052837195

SN - 1661-6596

VL - 19

JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

IS - 9

M1 - 2473

ER -

rs495139 in the TYMS-ENOSF1 region and risk of ovarian carcinoma of mucinous histology

Abstract

Keywords

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