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. © 2013 Macmillan Publishers Limited. All rights reserved.

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

BAGLIETTO, LAURA;
2013

Abstract

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. © 2013 Macmillan Publishers Limited. All rights reserved.
Permuth Wey, Jennifer; Lawrenson, Kate; Shen, Howard C.; Velkova, Aneliya; Tyrer, Jonathan P.; Chen, Zhihua; Lin, Hui Yi; Ann Chen, Y.; 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.; 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.; 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; Krüger Kjaer, Susanne; Kupryjanczyk, Jolanta; Lambrechts, Diether; Lambrechts, Sandrina; Lancaster, Johnathan M.; Le, Nhu D.; Leminen, Arto; Levine, Douglas A.; Liang, Dong; Kiong Lim, Boon; 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; Anne Rossing, Mary; 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; Ling Woo, Yin; 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.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11568/817821
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