| Literature DB >> 26399219 |
Ernest K Amankwah1,2, Hui-Yi Lin3, Jonathan P Tyrer4, Kate Lawrenson5, Joe Dennis4, Ganna Chornokur1, Katja K H Aben6,7, Hoda Anton-Culver8, Natalia Antonenkova9, Fiona Bruinsma10, Elisa V Bandera11, Yukie T Bean12,13, Matthias W Beckmann14, Maria Bisogna15, Line Bjorge16,17, Natalia Bogdanova18, Louise A Brinton19, Angela Brooks-Wilson20,21, Clareann H Bunker22, Ralf Butzow23,24, Ian G Campbell25,26,27, Karen Carty28,29, Zhihua Chen3, Y Ann Chen3, Jenny Chang-Claude30, Linda S Cook31, Daniel W Cramer32, Julie M Cunningham33, Cezary Cybulski34, Agnieszka Dansonka-Mieszkowska35, Andreas du Bois36,37, Evelyn Despierre38, Ed Dicks39, Jennifer A Doherty40,41, Thilo Dörk18, Matthias Dürst42, Douglas F Easton43,44, Diana M Eccles45, Robert P Edwards46, Arif B Ekici47, Peter A Fasching14,48, Brooke L Fridley49, Yu-Tang Gao50, Aleksandra Gentry-Maharaj51, Graham G Giles10,52, Rosalind Glasspool29, Marc T Goodman53,54, Jacek Gronwald34, Patricia Harrington39, Philipp Harter36,37, Hanis N Hasmad55, Alexander Hein14, Florian Heitz36,37, Michelle A T Hildebrandt56, Peter Hillemanns18, Claus K Hogdall57, Estrid Hogdall58,59, Satoyo Hosono60, Edwin S Iversen61, Anna Jakubowska34, Allan Jensen58, Bu-Tian Ji19, Beth Y Karlan62, Heather Jim63, Melissa Kellar12,13, Lambertus A Kiemeney6, Camilla Krakstad16,17, Susanne K Kjaer57,58, Jolanta Kupryjanczyk35, Diether Lambrechts64,65, Sandrina Lambrechts38, Nhu D Le66, Alice W Lee5, Shashi Lele67, Arto Leminen23, Jenny Lester62, Douglas A Levine15, Dong Liang68, Boon Kiong Lim69, Jolanta Lissowska70, Karen Lu71, Jan Lubinski34, Lene Lundvall57, Leon F A G Massuger72, Keitaro Matsuo60, Valerie McGuire73, John R McLaughlin74, Ian McNeish29, Usha Menon51, Roger L Milne10,52, Francesmary Modugno22,75,76, Kirsten B Moysich67, Roberta B Ness77, Heli Nevanlinna23, Ursula Eilber30, Kunle Odunsi78, Sara H Olson79, Irene Orlow79, Sandra Orsulic62, Rachel Palmieri Weber80, James Paul29, Celeste L Pearce5,81, Tanja Pejovic12,13, Liisa M Pelttari23, Jennifer Permuth-Wey1, Malcolm C Pike5,79, Elizabeth M Poole82,83, Harvey A Risch84, Barry Rosen85,86, Mary Anne Rossing41, Joseph H Rothstein73, Anja Rudolph30, Ingo B Runnebaum42, Iwona K Rzepecka35, Helga B Salvesen16,17, Eva Schernhammer82,83, Ira Schwaab87, Xiao-Ou Shu88, Yurii B Shvetsov89, Nadeem Siddiqui28, Weiva Sieh73, Honglin Song39, Melissa C Southey26, Beata Spiewankiewicz90, Lara Sucheston-Campbell67, Soo-Hwang Teo55,91, Kathryn L Terry32,83, Pamela J Thompson53,54, Lotte Thomsen92, Ingvild L Tangen16,17, Shelley S Tworoger32,83, Anne M van Altena72, Robert A Vierkant93, Ignace Vergote38, Christine S Walsh62, Shan Wang-Gohrke30, Nicolas Wentzensen19, Alice S Whittemore73, Kristine G Wicklund41, Lynne R Wilkens89, Anna H Wu5, Xifeng Wu56, Yin-Ling Woo69, Hannah Yang19, Wei Zheng94, Argyrios Ziogas8, Linda E Kelemen95, Andrew Berchuck96, Joellen M Schildkraut97, Susan J Ramus5, Ellen L Goode98, Alvaro N A Monteiro3, Simon A Gayther5, Steven A Narod99, Paul D P Pharoah43, Thomas A Sellers1, Catherine M Phelan1.
Abstract
Epithelial-mesenchymal transition (EMT) is a process whereby epithelial cells assume mesenchymal characteristics to facilitate cancer metastasis. However, EMT also contributes to the initiation and development of primary tumors. Prior studies that explored the hypothesis that EMT gene variants contribute to epithelial ovarian carcinoma (EOC) risk have been based on small sample sizes and none have sought replication in an independent population. We screened 15,816 single-nucleotide polymorphisms (SNPs) in 296 genes in a discovery phase using data from a genome-wide association study of EOC among women of European ancestry (1,947 cases and 2,009 controls) and identified 793 variants in 278 EMT-related genes that were nominally (P < 0.05) associated with invasive EOC. These SNPs were then genotyped in a larger study of 14,525 invasive-cancer patients and 23,447 controls. A P-value <0.05 and a false discovery rate (FDR) <0.2 were considered statistically significant. In the larger dataset, GPC6/GPC5 rs17702471 was associated with the endometrioid subtype among Caucasians (odds ratio (OR) = 1.16, 95% CI = 1.07-1.25, P = 0.0003, FDR = 0.19), whereas F8 rs7053448 (OR = 1.69, 95% CI = 1.27-2.24, P = 0.0003, FDR = 0.12), F8 rs7058826 (OR = 1.69, 95% CI = 1.27-2.24, P = 0.0003, FDR = 0.12), and CAPN13 rs1983383 (OR = 0.79, 95% CI = 0.69-0.90, P = 0.0005, FDR = 0.12) were associated with combined invasive EOC among Asians. In silico functional analyses revealed that GPC6/GPC5 rs17702471 coincided with DNA regulatory elements. These results suggest that EMT gene variants do not appear to play a significant role in the susceptibility to EOC.Entities:
Keywords: epithelial-mesenchymal transition; ovarian cancer; single-nucleotide polymorphisms
Mesh：
Year: 2015 PMID： 26399219 PMCID： PMC4721602 DOI： 10.1002/gepi.21921
Source DB: PubMed Journal: Genet Epidemiol ISSN： 0741-0395 Impact factor: 2.135