Genome-wide significant risk associations for mucinous ovarian carcinoma Journal Article
| Authors: | Kelemen, L. E.; Lawrenson, K.; Tyrer, J. P.; Lee, J. M.; Seo, J. H.; Phelan, C. M.; Beesley, J.; Chen, X.; Spindler, T. J.; Aben, K. K. H.; Anton-Culver, H.; Antonenkova, N.; Australian Cancer Study; Australian Ovarian Cancer Study Group; Bandera, E. V.; Bean, Y. T.; Beckmann, M. W.; Bisogna, M.; Bjorge, L.; Bogdanova, N.; Brinton, L. A.; Brooks-Wilson, A.; Bruinsma, F.; Butzow, R.; Campbell, I. G.; Carty, K.; Chang-Claude, J.; Chen, Y. A.; Chen, Z.; Cook, L. S.; Cramer, D. W.; Cunningham, J. M.; Cybulski, C.; Dansonka-Mieszkowska, A.; Dennis, J.; Dicks, E.; Doherty, J. A.; Dork, T.; du Bois, A.; Durst, M.; Eccles, D. M.; Easton, P. A.; Edwards, R. P.; Eilber, U.; Ekici, A. B.; Engelholm, S. A.; Fasching, P. A.; Frindley, B. L.; Gao, Y. T.; Gentry-Maharaj, A.; Giles, G. G.; Glasspool, R.; Goode, E. L.; Goodamn, M. T.; Gronwald, J.; Harrington, P.; Harter, P.; Hasmad, H. N.; Hein, A.; Heitz, F.; Hildebrandt, M. A. T.; Hillemanns, P.; Hogdall, E.; Hogdall, C. K.; Hosono, S.; Iversen, E.; Jakubowska, A.; Jensen, A.; Ji, B. T.; Karlan, B. Y.; Kellar, M.; Kelley, J. L.; Kiemeney, L. A.; Krakstad, C.; Kjaer, S. K.; Kupryjanczyk, J.; Lambrechts, D.; Lambrechts, S.; Le, N. D.; Lee, A. W.; Lele, S.; Leminen, A.; Lester, J.; Levine, D. A.; Liang, D.; Lissowska, J.; Lu, K.; Lubinski, J.; Lundvall, L.; Massuger, L. F. A. G.; Matsuo, K.; McGuire, V.; McLaughlin, J. R.; McNeish, I.; Menon, U.; Modugno, F.; Moes-Sosnowska, J.; Moysich, K. B.; Narod, S. A.; Nedergaard, L.; Ness, R. B.; Nevanlinna, H.; Adenan, N. A. M.; Odunsi, K.; Olson, S. H.; Orlow, I.; Orsulic, S.; Palmieri Weber, R.; Paul, J.; Pearce, C. L.; Pejovic, T.; Pelttari, L. M.; Permuth-Wey, J.; Pike, M. C.; Poole, E. M.; Ramus, S. J.; Risch, H. A.; Rosen, B.; Rossing, M. A.; Rothstein, J. H.; Rudolph, A.; Runnebaum, I B.; Rzepecka, I. K.; Salvesen, H. B.; Schildkraut, J. M.; Schwaab, I.; Shu, X. O.; Shvetsov, Y. B.; Siddiqui, N.; Sieh, W.; Song, H.; Southey, M. C.; Suchston, L.; Tangen, I. L.; Teo, S. H.; Terry, K. L.; Thompson, P. J.; Tworoger, S. S.; van Altena, A. M.; Van Nieuwenhuysen, E.; Vergote, I.; Vierkant, R. A.; Wang-Gohrke, S.; Walsh, C. S.; Wentzensen, N.; Whittemore, A. S.; Wicklund, K. G.; Wilkens, L. R.; Sawicki, W.; Woo, Y. L.; Wu, X.; Wu, A. H.; Yang, H.; Zheng, W.; Ziogas, A.; Sellers, T. A.; Freedman, M. L.; Chenevix-Trench, G.; Pharoah, P. D. P.; Gayther, S. A.; Berchuck, A.; for the Ovarian Cancer Association Consortium |
| Article Title: | Genome-wide significant risk associations for mucinous ovarian carcinoma |
| Abstract: | Genome-wide association studies have identified several risk associations for ovarian carcinomas but not for mucinous ovarian carcinomas (MOCs). Our analysis of 1,644 MOC cases and 21,693 controls with imputation identified 3 new risk associations: rs752590 at 2q13 (P = 3.3 × 10-8), rs711830 at 2q31.1 (P = 7.5 × 10-12) and rs688187 at 19q13.2 (P = 6.8 × 10-13). We identified significant expression quantitative trait locus (eQTL) associations for HOXD9 at 2q31.1 in ovarian (P = 4.95 × 10-4, false discovery rate (FDR) = 0.003) and colorectal (P = 0.01, FDR = 0.09) tumors and for PAX8 at 2q13 in colorectal tumors (P = 0.03, FDR = 0.09). Chromosome conformation capture analysis identified interactions between the HOXD9 promoter and risk-associated SNPs at 2q31.1. Overexpressing HOXD9 in MOC cells augmented the neoplastic phenotype. These findings provide the first evidence for MOC susceptibility variants and insights into the underlying biology of the disease. © 2015 Nature America, Inc. All rights reserved. |
| Keywords: | controlled study; major clinical study; promoter region; single nucleotide polymorphism; cancer risk; phenotype; allele; gene overexpression; gene expression; genetic association; genotype; gene frequency; in vitro study; colorectal carcinoma; genetic susceptibility; ovary carcinoma; 3' untranslated region; rna stability; conformational transition; colloid carcinoma; false positive result; rna polymerase ii; anchorage independent growth; quantitative trait locus; enhancer region; transcription factor pax8; human; female; priority journal; article; long untranslated rna; mucinous ovarian carcinoma |
| Journal Title: | Nature Genetics |
| Volume: | 47 |
| Issue: | 8 |
| ISSN: | 1061-4036 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2015-08-01 |
| Start Page: | 888 |
| End Page: | 897 |
| Language: | English |
| DOI: | 10.1038/ng.3336 |
| PROVIDER: | scopus |
| PMCID: | PMC4520768 |
| PUBMED: | 26075790 |
| DOI/URL: | |
| Notes: | Export Date: 2 September 2015 -- Source: Scopus |
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