Identification and molecular characterization of a new ovarian cancer susceptibility locus at 17q21.31.

Citation data:

Nature communications, ISSN: 2041-1723, Vol: 4, Issue: 1, Page: 1627

Publication Year:
2013
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Repository URL:
https://digitalcommons.dartmouth.edu/facoa/2759; https://ohsu.pure.elsevier.com/en/publications/8e5d93c8-b5ac-4735-8b4f-b1f4719485c0
PMID:
23535648
DOI:
10.1038/ncomms2613
PMCID:
PMC3709460; 3709460
Author(s):
Permuth-Wey, Jennifer; Lawrenson, Kate; Shen, Howard C; Velkova, Aneliya; Tyrer, Jonathan P; Chen, Zhihua; Lin, Hui-Yi; Chen, Y Ann; Tsai, Ya-Yu; Qu, Xiaotao; Ramus, Susan J; Karevan, Rod; Lee, Janet; Lee, Nathan; Larson, Melissa C; Aben, Katja K; Anton-Culver, Hoda; Antonenkova, Natalia; Antoniou, Antonis C; Armasu, Sebastian M; Australian Cancer Study; Australian Ovarian Cancer Study; Bacot, François; Baglietto, Laura; Bandera, Elisa V; Barnholtz-Sloan, Jill; Beckmann, Matthias W; Birrer, Michael J; Bloom, Greg; Bogdanova, Natalia; Brinton, Louise A; Brooks-Wilson, Angela; Brown, Robert; Butzow, Ralf; Cai, Qiuyin; Campbell, Ian; Chang-Claude, Jenny; Chanock, Stephen; Chenevix-Trench, Georgia; Cheng, Jin Q; Cicek, Mine S; Coetzee, Gerhard A; Consortium of Investigators of Modifiers of BRCA1/2; Cook, Linda S; Couch, Fergus J; Cramer, Daniel W; Cunningham, Julie M; Dansonka-Mieszkowska, Agnieszka; Despierre, Evelyn; Doherty, Jennifer A; Dörk, Thilo; du Bois, Andreas; Dürst, Matthias; Easton, Douglas F; Eccles, Diana; Edwards, Robert; Ekici, Arif B; Fasching, Peter A; Fenstermacher, David A; Flanagan, James M; Garcia-Closas, Montserrat; Gentry-Maharaj, Aleksandra; Giles, Graham G; Glasspool, Rosalind M; Gonzalez-Bosquet, Jesus; Goodman, Marc T; Gore, Martin; Górski, Bohdan; Gronwald, Jacek; Hall, Per; Halle, Mari K; Harter, Philipp; Heitz, Florian; Hillemanns, Peter; Hoatlin, Maureen; Høgdall, Claus K; Høgdall, Estrid; Hosono, Satoyo; Jakubowska, Anna; Jensen, Allan; Jim, Heather; Kalli, Kimberly R; Karlan, Beth Y; Kaye, Stanley B; Kelemen, Linda E; Kiemeney, Lambertus A; Kikkawa, Fumitaka; Konecny, Gottfried E; Krakstad, Camilla; Kjaer, Susanne Krüger; Kupryjanczyk, Jolanta; Lambrechts, Diether; Lambrechts, Sandrina; Lancaster, Johnathan M; Le, Nhu D; Leminen, Arto; Levine, Douglas A; Liang, Dong; Lim, Boon Kiong; Lin, Jie; Lissowska, Jolanta; Lu, Karen H; Lubiński, Jan; Lurie, Galina; Massuger, Leon F A G; Matsuo, Keitaro; McGuire, Valerie; McLaughlin, John R; Menon, Usha; Modugno, Francesmary; Moysich, Kirsten B; Nakanishi, Toru; Narod, Steven A; Nedergaard, Lotte; Ness, Roberta B; Nevanlinna, Heli; Nickels, Stefan; Noushmehr, Houtan; Odunsi, Kunle; Olson, Sara H; Orlow, Irene; Paul, James; Pearce, Celeste L; Pejovic, Tanja; Pelttari, Liisa M; Pike, Malcolm C; Poole, Elizabeth M; Raska, Paola; Renner, Stefan P; Risch, Harvey A; Rodriguez-Rodriguez, Lorna; Rossing, Mary Anne; Rudolph, Anja; Runnebaum, Ingo B; Rzepecka, Iwona K; Salvesen, Helga B; Schwaab, Ira; Severi, Gianluca; Shridhar, Viji; Shu, Xiao-Ou; Shvetsov, Yurii B; Sieh, Weiva; Song, Honglin; Southey, Melissa C; Spiewankiewicz, Beata; Stram, Daniel; Sutphen, Rebecca; Teo, Soo-Hwang; Terry, Kathryn L; Tessier, Daniel C; Thompson, Pamela J; Tworoger, Shelley S; van Altena, Anne M; Vergote, Ignace; Vierkant, Robert A; Vincent, Daniel; Vitonis, Allison F; Wang-Gohrke, Shan; Palmieri Weber, Rachel; Wentzensen, Nicolas; Whittemore, Alice S; Wik, Elisabeth; Wilkens, Lynne R; Winterhoff, Boris; Woo, Yin Ling; Wu, Anna H; Xiang, Yong-Bing; Yang, Hannah P; Zheng, Wei; Ziogas, Argyrios; Zulkifli, Famida; Phelan, Catherine M; Iversen, Edwin; Schildkraut, Joellen M; Berchuck, Andrew; Fridley, Brooke L; Goode, Ellen L; Pharoah, Paul D P; Monteiro, Alvaro N A; Sellers, Thomas A; Gayther, Simon A Show More Hide
Publisher(s):
Springer Nature; Nature Publishing Group
Tags:
Chemistry; Biochemistry, Genetics and Molecular Biology; Physics and Astronomy; multidisciplinary sciences; science & technology; genome-wide association; microrna expression; genetic-variants; functional annotation; site polymorphisms; parkinson-disease; common inversion; binding-sites; mapt region; risk; chromosomes; human; pair 17; female; genetic predisposition to disease; humans; neoplasms; glandular and epithelial; ovarian neoplasms; polymorphism; single nucleotide; australian cancer study; australian ovarian cancer study; consort; Biochemistry, Genetics and Molecular Biology(all); Chemistry(all); Physics and Astronomy(all); Medicine and Health Sciences
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article description
Epithelial ovarian cancer (EOC) has a heritable component that remains to be fully characterized. Most identified common susceptibility variants lie in non-protein-coding sequences. We hypothesized that variants in the 3' untranslated region at putative microRNA (miRNA)-binding sites represent functional targets that influence EOC susceptibility. Here, we evaluate the association between 767 miRNA-related single-nucleotide polymorphisms (miRSNPs) and EOC risk in 18,174 EOC cases and 26,134 controls from 43 studies genotyped through the Collaborative Oncological Gene-environment Study. We identify several miRSNPs associated with invasive serous EOC risk (odds ratio=1.12, P=10(-8)) mapping to an inversion polymorphism at 17q21.31. Additional genotyping of non-miRSNPs at 17q21.31 reveals stronger signals outside the inversion (P=10(-10)). Variation at 17q21.31 is associated with neurological diseases, and our collaboration is the first to report an association with EOC susceptibility. An integrated molecular analysis in this region provides evidence for ARHGAP27 and PLEKHM1 as candidate EOC susceptibility genes.