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

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

Nature communications (2013-03-29)

Jennifer Permuth-Wey, Kate Lawrenson, Howard C Shen, Aneliya Velkova, Jonathan P Tyrer, Zhihua Chen, Hui-Yi Lin, Y Ann Chen, Ya-Yu Tsai, Xiaotao Qu, Susan J Ramus, Rod Karevan, Janet Lee, Nathan Lee, Melissa C Larson, Katja K Aben, Hoda Anton-Culver, Natalia Antonenkova, Antonis C Antoniou, Sebastian M Armasu, François Bacot, Laura Baglietto, Elisa V Bandera, Jill Barnholtz-Sloan, Matthias W Beckmann, Michael J Birrer, Greg Bloom, Natalia Bogdanova, Louise A Brinton, Angela Brooks-Wilson, Robert Brown, Ralf Butzow, Qiuyin Cai, Ian Campbell, Jenny Chang-Claude, Stephen Chanock, Georgia Chenevix-Trench, Jin Q Cheng, Mine S Cicek, Gerhard A Coetzee, Linda S Cook, Fergus J Couch, Daniel W Cramer, Julie M Cunningham, Agnieszka Dansonka-Mieszkowska, Evelyn Despierre, Jennifer A Doherty, Thilo Dörk, Andreas du Bois, Matthias Dürst, Douglas F Easton, Diana Eccles, Robert Edwards, Arif B Ekici, Peter A Fasching, David A Fenstermacher, James M Flanagan, Montserrat Garcia-Closas, Aleksandra Gentry-Maharaj, Graham G Giles, Rosalind M Glasspool, Jesus Gonzalez-Bosquet, Marc T Goodman, Martin Gore, Bohdan Górski, Jacek Gronwald, Per Hall, Mari K Halle, Philipp Harter, Florian Heitz, Peter Hillemanns, Maureen Hoatlin, Claus K Høgdall, Estrid Høgdall, Satoyo Hosono, Anna Jakubowska, Allan Jensen, Heather Jim, Kimberly R Kalli, Beth Y Karlan, Stanley B Kaye, Linda E Kelemen, Lambertus A Kiemeney, Fumitaka Kikkawa, Gottfried E Konecny, Camilla Krakstad, Susanne Krüger Kjaer, Jolanta Kupryjanczyk, Diether Lambrechts, Sandrina Lambrechts, Johnathan M Lancaster, Nhu D Le, Arto Leminen, Douglas A Levine, Dong Liang, Boon Kiong Lim, Jie Lin, Jolanta Lissowska, Karen H Lu, Jan Lubiński

PMID23535648

摘要

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.