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


Authors: Kelemen, L. E.; Earp, M.; Fridley, B. L.; Chenevix-Trench, G.; on behalf of the Australian Ovarian Cancer Study Group; 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.; Dörk, 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.; Southey, M. C.; Hildebrandt, M. A. T.; Liang, D.; Lu, K.; Wu, X.; Sellers, T. A.; Levine, D. A.; Schildkraut, J. M.; Iversen, E. S.; Terry, K. L.; Cramer, D. W.; Tworoger, S. S.; Poole, E. M.; Bandera, E. V.; Olson, S. H.; Orlow, I.; Thomsen, L. C. V.; Bjorge, L.; Krakstad, C.; Tangen, I. L.; Kiemeney, L. A.; Aben, K. K. H.; Massuger, L. F. A. G.; van Altena, A. M.; Pejovic, T.; Bean, Y.; Kellar, M.; Cook, L. S.; Le, N. D.; Brooks-Wilson, A.; Gronwald, J.; Cybulski, C.; Jakubowska, A.; Lubiński, J.; Wentzensen, N.; Brinton, L. A.; Lissowska, J.; Hogdall, E.; Engelholm, S. A.; Hogdall, C.; Lundvall, L.; Nedergaard, L.; Pharoah, P. D. P.; Dicks, E.; Song, H.; Tyrer, J. P.; McNeish, I.; Siddiqui, N.; Carty, K.; Glasspool, R.; Paul, J.; Campbell, I. G.; Eccles, D.; Whittemore, A. S.; McGuire, V.; Rothstein, J. H.; Sieh, W.; Narod, S. A.; Phelan, C. M.; McLaughlin, J. R.; Risch, H. A.; Anton-Culver, H.; Ziogas, A.; Menon, U.; Gayther, S. A.; Gentry-Maharaj, A.; Ramus, S. J.; Wu, A. H.; Pearce, C. L.; Lee, A. W.; Pike, M. C.; Kupryjanczyk, J.; Podgorska, A.; Plisiecka-Halasa, J.; Sawicki, W.; Goode, E. L.; Berchuck, A.; Ovarian Cancer Association Consortium
Article 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. © 2018 by the authors. Licensee MDPI, Basel, Switzerland.
Keywords: genetics; ovarian neoplasms; thymidylate synthase; gynecology; single-nucleotide polymorphism; consortia; expression quantitative trait locus; enolase superfamily member 1
Journal Title: International Journal of Molecular Sciences
Volume: 19
Issue: 9
ISSN: 1422-0067
Publisher: MDPI  
Date Published: 2018-09-01
Start Page: 2473
Language: English
DOI: 10.3390/ijms19092473
PROVIDER: scopus
PUBMED: 30134598
DOI/URL:
Notes: Article -- Export Date: 1 October 2018 -- Source: Scopus
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MSK Authors
  1. Malcolm Pike
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  2. Sara H Olson
    213 Olson
  3. Irene Orlow
    192 Orlow