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

Authors:
Dr Madalene Earp, PhD
Dr Madalene Earp, PhD
University of Calgary
Research Associate
Cancer genetics, palliative care
Calgary , Alberta | Canada
Linda E Kelemen Brooke L Fridley Georgia Chenevix-Trench Peter A Fasching Matthias W Beckmann Arif B Ekici Alexander Hein Diether Lambrechts Sandrina Lambrechts Els Van Nieuwenhuysen Ignace Vergote Mary Anne Rossing Jennifer A Doherty Jenny Chang-Claude Sabine Behrens Kirsten B Moysich Rikki Cannioto Shashikant Lele Kunle Odunsi Marc T Goodman Yurii B Shvetsov Pamela J Thompson Lynne R Wilkens Thilo Dörk Natalia Antonenkova Natalia Bogdanova Peter Hillemanns Ingo B Runnebaum Andreas du Bois Philipp Harter Florian Heitz Ira Schwaab Ralf Butzow Liisa M Pelttari Heli Nevanlinna Francesmary Modugno Robert P Edwards Joseph L Kelley Roberta B Ness Beth Y Karlan Jenny Lester Sandra Orsulic Christine Walsh Susanne K Kjaer Allan Jensen Julie M Cunningham Robert A Vierkant Graham G Giles Fiona Bruinsma Melissa C Southey Michelle A T Hildebrandt Dong Liang Karen Lu Xifeng Wu Thomas A Sellers Douglas A Levine Joellen M Schildkraut Edwin S Iversen Kathryn L Terry Daniel W Cramer Shelley S Tworoger Elizabeth M Poole Elisa V Bandera Sara H Olson Irene Orlow Liv Cecilie Vestrheim Thomsen Line Bjorge Camilla Krakstad Ingvild L Tangen Lambertus A Kiemeney Katja K H Aben Leon F A G Massuger Anne M van Altena Tanja Pejovic Yukie Bean Melissa Kellar Linda S Cook Nhu D Le Angela Brooks-Wilson Jacek Gronwald Cezary Cybulski Anna Jakubowska Jan Lubiński Nicolas Wentzensen Louise A Brinton Jolanta Lissowska Estrid Hogdall Svend Aage Engelholm Claus Hogdall Lene Lundvall Lotte Nedergaard Paul D P Pharoah Ed Dicks Honglin Song Jonathan P Tyrer Iain McNeish Nadeem Siddiqui Karen Carty Rosalind Glasspool James Paul Ian G Campbell Diana Eccles Alice S Whittemore Valerie McGuire Joseph H Rothstein Weiva Sieh Steven A Narod Catherine M Phelan John R McLaughlin Harvey A Risch Hoda Anton-Culver Argyrios Ziogas Usha Menon Simon A Gayther Aleksandra Gentry-Maharaj Susan J Ramus Anna H Wu Celeste Leigh Pearce Alice W Lee Malcolm C Pike Jolanta Kupryjanczyk Agnieszka Podgorska Joanna Plisiecka-Halasa Wlodzimierz Sawicki Ellen L Goode Andrew Berchuck

Int J Mol Sci 2018 Aug 21;19(9). Epub 2018 Aug 21.

Department of Obstetrics and Gynecology, Duke University Medical Center, Durham, NC 27710, USA.

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 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; = 0.15; N = 665 cases). Meta-analysis suggested a weak association (OR = 1.13; 95% CI = 1.03⁻1.24; = 0.01; N = 1019 cases). No significant association with risk of other OC histologic types was observed ( = 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 ( = 0.51, = 1.7 × 10), 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.

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Source
http://www.mdpi.com/1422-0067/19/9/2473
Publisher Site
http://dx.doi.org/10.3390/ijms19092473DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6163881PMC
August 2018
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2.862 Impact Factor

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