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

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 funct...

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Detalles Bibliográficos
Autores principales: 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, 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, 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, Vijayalakshmi, 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, Weber, Rachel Palmieri, 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2013
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3709460/
https://www.ncbi.nlm.nih.gov/pubmed/23535648
http://dx.doi.org/10.1038/ncomms2613
Descripción
Sumario: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 binding site 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 (OR=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 associates 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.

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