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

Publication ,  Journal Article
Kelemen, LE; Earp, M; Fridley, BL; Chenevix-Trench, G; Australian Ovarian Cancer Study Group; Fasching, PA; Beckmann, MW; Ekici, AB; Hein, A ...
Published in: Int J Mol Sci
August 21, 2018
Published version (DOI) Link to item

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.

Duke Scholars

Joellen Martha Schildkraut
Author Joellen Martha Schildkraut Family Medicine and Community Health, Prevention Research
Edwin Severin Iversen Jr.
Author Edwin Severin Iversen Jr. Statistical Science
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Published In

Int J Mol Sci

DOI

10.3390/ijms19092473

EISSN

1422-0067

Publication Date

August 21, 2018

Volume

19

Issue

9

Location

Switzerland

Related Subject Headings

  • Thymidylate Synthase
  • Signal Transduction
  • Risk
  • RNA, Antisense
  • Quantitative Trait Loci
  • Proteins
  • Polymorphism, Single Nucleotide
  • Ovarian Neoplasms
  • Odds Ratio
  • Middle Aged
 

Citation

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Kelemen, L. E., Earp, M., Fridley, B. L., Chenevix-Trench, G., Australian Ovarian Cancer Study Group, Fasching, P. A., … Ovarian Cancer Association Consortium. (2018). rs495139 in the TYMS-ENOSF1 Region and Risk of Ovarian Carcinoma of Mucinous Histology. Int J Mol Sci, 19(9). https://doi.org/10.3390/ijms19092473
Kelemen, Linda E., Madalene Earp, Brooke L. Fridley, Georgia Chenevix-Trench, Australian Ovarian Cancer Study Group, Peter A. Fasching, Matthias W. Beckmann, et al. “rs495139 in the TYMS-ENOSF1 Region and Risk of Ovarian Carcinoma of Mucinous Histology.” Int J Mol Sci 19, no. 9 (August 21, 2018). https://doi.org/10.3390/ijms19092473.
Kelemen LE, Earp M, Fridley BL, Chenevix-Trench G, Australian Ovarian Cancer Study Group, Fasching PA, et al. rs495139 in the TYMS-ENOSF1 Region and Risk of Ovarian Carcinoma of Mucinous Histology. Int J Mol Sci. 2018 Aug 21;19(9).
Kelemen, Linda E., et al. “rs495139 in the TYMS-ENOSF1 Region and Risk of Ovarian Carcinoma of Mucinous Histology.” Int J Mol Sci, vol. 19, no. 9, Aug. 2018. Pubmed, doi:10.3390/ijms19092473.
Kelemen LE, Earp M, Fridley BL, Chenevix-Trench G, Australian Ovarian Cancer Study Group, Fasching PA, Beckmann MW, 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, Dörk 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, Vestrheim Thomsen LC, 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, Lubiński 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, Ovarian Cancer Association Consortium. rs495139 in the TYMS-ENOSF1 Region and Risk of Ovarian Carcinoma of Mucinous Histology. Int J Mol Sci. 2018 Aug 21;19(9).

Published In

Int J Mol Sci

DOI

10.3390/ijms19092473

EISSN

1422-0067

Publication Date

August 21, 2018

Volume

19

Issue

9

Location

Switzerland

Related Subject Headings

  • Thymidylate Synthase
  • Signal Transduction
  • Risk
  • RNA, Antisense
  • Quantitative Trait Loci
  • Proteins
  • Polymorphism, Single Nucleotide
  • Ovarian Neoplasms
  • Odds Ratio
  • Middle Aged