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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Permuth-Wey, J; Lawrenson, K; Shen, HC; Velkova, A; Tyrer, JP; Chen, Z; Lin, H-Y; Chen, YA; Tsai, Y-Y; Qu, X; Ramus, SJ; Karevan, R; Lee, J; Lee, N; Larson, MC; Aben, KK; Anton-Culver, H; Antonenkova, N; Antoniou, AC; Armasu, SM; Australian Cancer Study, ; Australian Ovarian Cancer Study, ; Bacot, F; Baglietto, L; Bandera, EV; Barnholtz-Sloan, J; Beckmann, MW; Birrer, MJ; Bloom, G; Bogdanova, N; Brinton, LA; Brooks-Wilson, A; Brown, R; Butzow, R; Cai, Q; Campbell, I; Chang-Claude, J; Chanock, S; Chenevix-Trench, G; Cheng, JQ; Cicek, MS; Coetzee, GA; Consortium of Investigators of Modifiers of BRCA1/2, ; Cook, LS; Couch, FJ; Cramer, DW; Cunningham, JM; Dansonka-Mieszkowska, A; Despierre, E; Doherty, JA; Dörk, T; du Bois, A; Dürst, M; Easton, DF; Eccles, D; Edwards, R; Ekici, AB; Fasching, PA; Fenstermacher, DA; Flanagan, JM; Garcia-Closas, M; Gentry-Maharaj, A; Giles, GG; Glasspool, RM; Gonzalez-Bosquet, J; Goodman, MT; Gore, M; Górski, B; Gronwald, J; Hall, P; Halle, MK; Harter, P; Heitz, F; Hillemanns, P; Hoatlin, M; Høgdall, CK; Høgdall, E; Hosono, S; Jakubowska, A; Jensen, A; Jim, H; Kalli, KR; Karlan, BY; Kaye, SB; Kelemen, LE; Kiemeney, LA; Kikkawa, F; Konecny, GE; Krakstad, C; Kjaer, SK; Kupryjanczyk, J; Lambrechts, D; Lambrechts, S; Lancaster, JM; Le, ND; Leminen, A; Levine, DA; Liang, D; Lim, BK; Lin, J; Lissowska, J; Lu, KH; LubiƄski, J; Lurie, G; Massuger, LFAG; Matsuo, K; McGuire, V; McLaughlin, JR; Menon, U; Modugno, F; Moysich, KB; Nakanishi, T; Narod, SA; Nedergaard, L; Ness, RB; Nevanlinna, H; Nickels, S; Noushmehr, H; Odunsi, K; Olson, SH; Orlow, I; Paul, J; Pearce, CL; Pejovic, T; Pelttari, LM; Pike, MC; Poole, EM; Raska, P; Renner, SP; Risch, HA; Rodriguez-Rodriguez, L; Rossing, MA; Rudolph, A; Runnebaum, IB; Rzepecka, IK; Salvesen, HB; Schwaab, I; Severi, G; Shridhar, V; Shu, X-O; Shvetsov, YB; Sieh, W; Song, H; Southey, MC; Spiewankiewicz, B; Stram, D; Sutphen, R; Teo, S-H; Terry, KL; Tessier, DC; Thompson, PJ; Tworoger, SS; van Altena, AM; Vergote, I; Vierkant, RA; Vincent, D; Vitonis, AF; Wang-Gohrke, S; Palmieri Weber, R; Wentzensen, N; Whittemore, AS; Wik, E; Wilkens, LR; Winterhoff, B; Woo, YL; Wu, AH; Xiang, Y-B; Yang, HP; Zheng, W; Ziogas, A; Zulkifli, F; Phelan, CM; Iversen, E; Schildkraut, JM; Berchuck, A; Fridley, BL; Goode, EL; Pharoah, PDP; Monteiro, ANA; Sellers, TA; Gayther, SA

Published Date

  • January 2013

Published In

Volume / Issue

  • 4 /

Start / End Page

  • 1627 -

PubMed ID

  • 23535648

Pubmed Central ID

  • 23535648

Electronic International Standard Serial Number (EISSN)

  • 2041-1723

International Standard Serial Number (ISSN)

  • 2041-1723

Digital Object Identifier (DOI)

  • 10.1038/ncomms2613

Language

  • eng