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

Kelemen, L. E. et al. (2018) rs495139 in the TYMS-ENOSF1 region and risk of ovarian carcinoma of mucinous histology. International Journal of Molecular Sciences, 19(9), 2473. (doi: 10.3390/ijms19092473) (PMID:30134598) (PMCID:PMC6163881)

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 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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Glasspool, Dr Rosalind and Paul, Mr James and Carty, Mrs Karen
• Authors: Kelemen, L. E., Earp, M., Fridley, B. L., Chenevix-Trench, G., 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., Vestrheim Thomsen, L. C., 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., and Berchuck, A.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences; College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
• Journal Name: International Journal of Molecular Sciences
• Publisher: MDPI
• ISSN: 1661-6596
• ISSN (Online): 1422-0067
• Published Online: 21 August 2018
• Copyright Holders: Copyright © 2018 The Authors
• First Published: First published in International Journal of Molecular Sciences 19(9): 2473
• Publisher Policy: Reproduced under a Creative Commons License