Research
Print page Print page
Switch language
The Capital Region of Denmark - a part of Copenhagen University Hospital
Published

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

Research output: Contribution to journalJournal articleResearchpeer-review

DOI

  1. The Effects of Dual GLP-1/GIP Receptor Agonism on Glucagon Secretion-A Review

    Research output: Contribution to journalReviewResearchpeer-review

  2. Glucagon Receptor Signaling and Glucagon Resistance

    Research output: Contribution to journalReviewResearchpeer-review

  3. Evolution and Medical Significance of LU Domain-Containing Proteins

    Research output: Contribution to journalReviewResearchpeer-review

  4. Muscle-Saturated Bioactive Lipids Are Increased with Aging and Influenced by High-Intensity Interval Training

    Research output: Contribution to journalJournal articleResearchpeer-review

  5. 5hmC Level Predicts Biochemical Failure Following Radical Prostatectomy in Prostate Cancer Patients with ERG Negative Tumors

    Research output: Contribution to journalJournal articleResearchpeer-review

  1. Shared heritability and functional enrichment across six solid cancers

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Human papillomavirus and p16 in squamous cell carcinoma and intraepithelial neoplasia of the vagina

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. A Comprehensive Gene-Environment Interaction Analysis in Ovarian Cancer using Genome-wide Significant Common Variants

    Research output: Contribution to journalJournal articleResearchpeer-review

  4. Characterization of Human Adrenal Steroidogenesis during Fetal Development

    Research output: Contribution to journalJournal articleResearchpeer-review

View graph of relations

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 languageEnglish
JournalInternational Journal of Molecular Sciences
Volume19
Issue number9
Pages (from-to)2473
ISSN1661-6596
DOIs
Publication statusPublished - 21 Aug 2018

    Research areas

  • Adenocarcinoma, Mucinous/genetics, Case-Control Studies, Female, Gene Expression Regulation, Neoplastic, Genetic Association Studies, Humans, Logistic Models, Middle Aged, Odds Ratio, Ovarian Neoplasms/genetics, Polymorphism, Single Nucleotide, Proteins/genetics, Quantitative Trait Loci, RNA, Antisense/genetics, Risk, Signal Transduction, Thymidylate Synthase/genetics

ID: 55849039