Identification and molecular characterization of a new ovarian cancer susceptibility locus at 17q21.31 Journal Article
| Authors: | Permuth-Wey, J.; Lawrenson, K.; Shen, H. C.; Velkova, A.; Tyrer, J. P.; Chen, Z.; Lin, H. Y.; Ann Chen, Y.; Tsai, Y. Y.; Qu, X.; Ramus, S. J.; Karevan, R.; Lee, J.; Lee, N.; Larson, M. C.; Aben, K. K.; Anton-Culver, H.; Antonenkova, N.; Antoniou, A. C.; Armasu, S. M.; Bacot, F.; Baglietto, L.; Bandera, E. V.; Barnholtz-Sloan, J.; Beckmann, M. W.; Birrer, M. J.; Bloom, G.; Bogdanova, N.; Brinton, L. A.; Brooks-Wilson, A.; Brown, R.; Butzow, R.; Cai, Q.; Campbell, I.; Chang-Claude, J.; Chanock, S.; Chenevix-Trench, G.; Cheng, J. Q.; Cicek, M. S.; Coetzee, G. A.; Cook, L. S.; Couch, F. J.; Cramer, D. W.; Cunningham, J. M.; Dansonka-Mieszkowska, A.; Despierre, E.; Doherty, J. A.; Dörk, T.; du Bois, A.; Dürst, M.; Easton, D. F.; Eccles, D.; Edwards, R.; Ekici, A. B.; Fasching, P. A.; Fenstermacher, D. A.; Flanagan, J. M.; Garcia-Closas, M.; Gentry-Maharaj, A.; Giles, G. G.; Glasspool, R. M.; Gonzalez-Bosquet, J.; Goodman, M. T.; Gore, M.; Górski, B.; Gronwald, J.; Hall, P.; Halle, M. K.; Harter, P.; Heitz, F.; Hillemanns, P.; Hoatlin, M.; Høgdall, C. K.; Høgdall, E.; Hosono, S.; Jakubowska, A.; Jensen, A.; Jim, H.; Kalli, K. R.; Karlan, B. Y.; Kaye, S. B.; Kelemen, L. E.; Kiemeney, L. A.; Kikkawa, F.; Konecny, G. E.; Krakstad, C.; Krüger Kjaer, S.; Kupryjanczyk, J.; Lambrechts, D.; Lambrechts, S.; Lancaster, J. M.; Le, N. D.; Leminen, A.; Levine, D. A.; Liang, D.; Kiong Lim, B.; Lin, J.; Lissowska, J.; Lu, K. H.; Lubinski, J.; Olson, S. H.; Orlow, I.; Pike, M. C. |
| Article Title: | Identification and molecular characterization of a new ovarian cancer susceptibility locus at 17q21.31 |
| 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. |
| Keywords: | controlled study; unclassified drug; major clinical study; single nucleotide polymorphism; polymorphism, single nucleotide; cancer risk; molecular genetics; ovarian neoplasms; cancer susceptibility; genetic predisposition to disease; ovary cancer; microrna; protein; gene locus; genetic association; genetic variability; genotype; membrane protein; molecular analysis; binding site; 3' untranslated region; neurologic disease; chromosome 17q; neurology; genetic identification; neoplasms, glandular and epithelial; hypothesis; chromosomes, human, pair 17; genotype environment interaction; arh protein; gap27 protein; plekhm 1 protein |
| Journal Title: | Nature Communications |
| Volume: | 4 |
| ISSN: | 2041-1723 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2013-01-01 |
| Start Page: | 1627 |
| Language: | English |
| PROVIDER: | scopus |
| PUBMED: | 23535648 |
| DOI: | 10.1038/ncomms2613 |
| PMCID: | PMC3709460 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 1 May 2013" - ":doi 10.1038/ncomms2613" - "Source: Scopus" |
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