Résumé
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.
langue originale | Anglais |
---|---|
Numéro d'article | 1627 |
journal | Nature Communications |
Volume | 4 |
Les DOIs | |
état | Publié - 11 avr. 2013 |
Modification externe | Oui |
Contient cette citation
- APA
- Author
- BIBTEX
- Harvard
- Standard
- RIS
- Vancouver
}
Dans: Nature Communications, Vol 4, 1627, 11.04.2013.
Résultats de recherche: Contribution à un journal › Article › Revue par des pairs
TY - JOUR
T1 - Identification and molecular characterization of a new ovarian cancer susceptibility locus at 17q21.31
AU - Permuth-Wey, Jennifer
AU - Lawrenson, Kate
AU - Shen, Howard C.
AU - Velkova, Aneliya
AU - Tyrer, Jonathan P.
AU - Chen, Zhihua
AU - Lin, Hui Yi
AU - Ann Chen, Y.
AU - Tsai, Ya Yu
AU - Qu, Xiaotao
AU - Ramus, Susan J.
AU - Karevan, Rod
AU - Lee, Janet
AU - Lee, Nathan
AU - Larson, Melissa C.
AU - Aben, Katja K.
AU - Anton-Culver, Hoda
AU - Antonenkova, Natalia
AU - Antoniou, Antonis C.
AU - Armasu, Sebastian M.
AU - Bacot, François
AU - Baglietto, Laura
AU - Bandera, Elisa V.
AU - Barnholtz-Sloan, Jill
AU - Beckmann, Matthias W.
AU - Birrer, Michael J.
AU - Bloom, Greg
AU - Bogdanova, Natalia
AU - Brinton, Louise A.
AU - Brooks-Wilson, Angela
AU - Brown, Robert
AU - Butzow, Ralf
AU - Cai, Qiuyin
AU - Campbell, Ian
AU - Chang-Claude, Jenny
AU - Chanock, Stephen
AU - Chenevix-Trench, Georgia
AU - Cheng, Jin Q.
AU - Cicek, Mine S.
AU - Coetzee, Gerhard A.
AU - Cook, Linda S.
AU - Couch, Fergus J.
AU - Cramer, Daniel W.
AU - Cunningham, Julie M.
AU - Dansonka-Mieszkowska, Agnieszka
AU - Despierre, Evelyn
AU - Doherty, Jennifer A.
AU - Dörk, Thilo
AU - Du Bois, Andreas
AU - Dürst, Matthias
AU - Easton, Douglas F.
AU - Eccles, Diana
AU - Edwards, Robert
AU - Ekici, Arif B.
AU - Fasching, Peter A.
AU - Fenstermacher, David A.
AU - Flanagan, James M.
AU - Garcia-Closas, Montserrat
AU - Gentry-Maharaj, Aleksandra
AU - Giles, Graham G.
AU - Glasspool, Rosalind M.
AU - Gonzalez-Bosquet, Jesus
AU - Goodman, Marc T.
AU - Gore, Martin
AU - Górski, Bohdan
AU - Gronwald, Jacek
AU - Hall, Per
AU - Halle, Mari K.
AU - Harter, Philipp
AU - Heitz, Florian
AU - Hillemanns, Peter
AU - Hoatlin, Maureen
AU - Høgdall, Claus K.
AU - Høgdall, Estrid
AU - Hosono, Satoyo
AU - Jakubowska, Anna
AU - Jensen, Allan
AU - Jim, Heather
AU - Kalli, Kimberly R.
AU - Karlan, Beth Y.
AU - Kaye, Stanley B.
AU - Kelemen, Linda E.
AU - Kiemeney, Lambertus A.
AU - Kikkawa, Fumitaka
AU - Konecny, Gottfried E.
AU - Krakstad, Camilla
AU - Krüger Kjaer, Susanne
AU - Kupryjanczyk, Jolanta
AU - Lambrechts, Diether
AU - Lambrechts, Sandrina
AU - Lancaster, Johnathan M.
AU - Le, Nhu D.
AU - Leminen, Arto
AU - Levine, Douglas A.
AU - Liang, Dong
AU - Kiong Lim, Boon
AU - Lin, Jie
AU - Lissowska, Jolanta
AU - Lu, Karen H.
AU - Lubiński, Jan
AU - Lurie, Galina
AU - Massuger, Leon F.A.G.
AU - Matsuo, Keitaro
AU - McGuire, Valerie
AU - McLaughlin, John R.
AU - Menon, Usha
AU - Modugno, Francesmary
AU - Moysich, Kirsten B.
AU - Nakanishi, Toru
AU - Narod, Steven A.
AU - Nedergaard, Lotte
AU - Ness, Roberta B.
AU - Nevanlinna, Heli
AU - Nickels, Stefan
AU - Noushmehr, Houtan
AU - Odunsi, Kunle
AU - Olson, Sara H.
AU - Orlow, Irene
AU - Paul, James
AU - Pearce, Celeste L.
AU - Pejovic, Tanja
AU - Pelttari, Liisa M.
AU - Pike, Malcolm C.
AU - Poole, Elizabeth M.
AU - Raska, Paola
AU - Renner, Stefan P.
AU - Risch, Harvey A.
AU - Rodriguez-Rodriguez, Lorna
AU - Anne Rossing, Mary
AU - Rudolph, Anja
AU - Runnebaum, Ingo B.
AU - Rzepecka, Iwona K.
AU - Salvesen, Helga B.
AU - Schwaab, Ira
AU - Severi, Gianluca
AU - Shridhar, Viji
AU - Shu, Xiao Ou
AU - Shvetsov, Yurii B.
AU - Sieh, Weiva
AU - Song, Honglin
AU - Southey, Melissa C.
AU - Spiewankiewicz, Beata
AU - Stram, Daniel
AU - Sutphen, Rebecca
AU - Teo, Soo Hwang
AU - Terry, Kathryn L.
AU - Tessier, Daniel C.
AU - Thompson, Pamela J.
AU - Tworoger, Shelley S.
AU - Van Altena, Anne M.
AU - Vergote, Ignace
AU - Vierkant, Robert A.
AU - Vincent, Daniel
AU - Vitonis, Allison F.
AU - Wang-Gohrke, Shan
AU - Palmieri Weber, Rachel
AU - Wentzensen, Nicolas
AU - Whittemore, Alice S.
AU - Wik, Elisabeth
AU - Wilkens, Lynne R.
AU - Winterhoff, Boris
AU - Ling Woo, Yin
AU - Wu, Anna H.
AU - Xiang, Yong Bing
AU - Yang, Hannah P.
AU - Zheng, Wei
AU - Ziogas, Argyrios
AU - Zulkifli, Famida
AU - Phelan, Catherine M.
AU - Iversen, Edwin
AU - Schildkraut, Joellen M.
AU - Berchuck, Andrew
AU - Fridley, Brooke L.
AU - Goode, Ellen L.
AU - Pharoah, Paul D.P.
AU - Monteiro, Alvaro N.A.
AU - Sellers, Thomas A.
AU - Gayther, Simon A.
PY - 2013/4/11
Y1 - 2013/4/11
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84875908264&partnerID=8YFLogxK
U2 - 10.1038/ncomms2613
DO - 10.1038/ncomms2613
M3 - Article
C2 - 23535648
AN - SCOPUS:84875908264
SN - 2041-1723
VL - 4
JO - Nature Communications
JF - Nature Communications
M1 - 1627
ER -