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Title: Epithelial-Mesenchymal Transition (EMT) Gene Variants and Epithelial Ovarian Cancer (EOC) Risk.
Authors: Amankwah EK,  Lin HY,  Tyrer JP,  Lawrenson K,  Dennis J,  Chornokur G,  Aben KK,  Anton-Culver H,  Antonenkova N,  Bruinsma F,  Bandera EV,  Bean YT,  Beckmann MW,  Bisogna M,  Bjorge L,  Bogdanova N,  Brinton LA,  Brooks-Wilson A,  Bunker CH,  Butzow R,  Campbell IG,  Carty K,  Chen Z,  Chen YA,  Chang-Claude J,  Cook LS,  Cramer DW,  Cunningham JM,  Cybulski C,  Dansonka-Mieszkowska A,  du Bois A,  Despierre E,  Dicks E,  Doherty JA,  Dörk T,  Dürst M,  Easton DF,  Eccles DM,  Edwards RP,  Ekici AB,  Fasching PA,  Fridley BL,  Gao YT,  Gentry-Maharaj A,  Giles GG,  Glasspool R,  Goodman MT,  Gronwald J,  Harrington P,  Harter P,  Hasmad HN,  Hein A,  Heitz F,  Hildebrandt MA,  Hillemanns P,  Hogdall CK,  Hogdall E,  Hosono S,  Iversen ES,  Jakubowska A,  Jensen A,  Ji BT,  Karlan BY,  Jim H,  Kellar M,  Kiemeney LA,  Krakstad C,  Kjaer SK,  Kupryjanczyk J,  Lambrechts D,  Lambrechts S,  Le ND,  Lee AW,  Lele S,  Leminen A,  Lester J,  Levine DA,  Liang D,  Lim BK,  Lissowska J,  Lu K,  Lubinski J,  Lundvall L,  Massuger LF,  Matsuo K,  McGuire V,  McLaughlin JR,  McNeish I,  Menon U,  Milne RL,  Modugno F,  Moysich KB,  Ness RB,  Nevanlinna H,  Eilber U,  Odunsi K,  Olson SH,  Orlow I,  Orsulic S,  Weber RP,  Paul J,  Pearce CL,  Pejovic T,  Pelttari LM,  Permuth-Wey J,  Pike MC,  Poole EM,  Risch HA,  Rosen B,  Rossing MA,  Rothstein JH,  Rudolph A,  Runnebaum IB,  Rzepecka IK,  Salvesen HB,  Schernhammer E,  Schwaab I,  Shu XO,  Shvetsov YB,  Siddiqui N,  Sieh W,  Song H,  Southey MC,  Spiewankiewicz B,  Sucheston-Campbell L,  Teo SH,  Terry KL,  Thompson PJ,  Thomsen L,  Tangen IL,  Tworoger SS,  van Altena AM,  Vierkant RA,  Vergote I,  Walsh CS,  Wang-Gohrke S,  Wentzensen N,  Whittemore AS,  Wicklund KG,  Wilkens LR,  Wu AH,  Wu X,  Woo YL,  Yang H,  Zheng W,  Ziogas A,  Kelemen LE,  Berchuck A,  Georgia Chenevix-Trench on behalf of the AOCS management group,  Schildkraut JM,  Ramus SJ,  Goode EL,  Monteiro AN,  Gayther SA,  Narod SA,  Pharoah PD,  Sellers TA,  Phelan CM
Journal: Genet Epidemiol
Date: 2015 Dec
Branches: CGB, MEB, OD, OEEB
PubMed ID: 26399219
PMC ID: PMC4721602
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.