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

• Verfasst von: Permuth-Wey, Jennifer [VerfasserIn]
• Verfasst von: Chang-Claude, Jenny [VerfasserIn]
• Verfasst von: Nickels, Stefan [VerfasserIn]
• Verfasst von: Rudolph, Anja [VerfasserIn]
• Titel: Identification and molecular characterization of a new ovarian cancer susceptibility locus at 17q21.31
• Verf.angabe: Jennifer Permuth-Wey, Kate Lawrenson, Howard C. Shen et al.*
• E-Jahr: 2013
• Jahr: 27 Mar 2013
• Umfang: 12 S.
• Fussnoten: *Et al.: Jenny Chang-Claude, Stefan Nickels, Anja Rudolph [und 172 weitere] ; Gesehen am 10.01.2022
• Titel Quelle: Enthalten in: Nature Communications
• Ort Quelle: [London] : Nature Publishing Group UK, 2010
• Jahr Quelle: 2013
• Band/Heft Quelle: 4(2013), Artikel-ID 1627, Seite 1-12
• ISSN Quelle: 2041-1723
• DOI: doi:10.1038/ncomms2613
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: Cancer genetics
• Sach-SW: Genetic association study
• Sach-SW: Ovarian cancer
• K10plus-PPN: 1785259016

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.