Epithelial-Mesenchymal Transition (EMT) Gene Variants and Epithelial Ovarian Cancer (EOC) Risk

Amankwah EK, Lin HY, Tyrer JP, Lawrenson K, Dennis J, Chornokur G, Aben KKH, Anton-Culver H, Antonenkova N, Bruinsma F, Bandera EV, Bean YT, Beckmann M, 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, Doerk T, Duerst M, Easton DF, Eccles DM, Edwards RP, Ekici AB, Fasching P, 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 MAT, 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 LFAG, 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, Schildkraut JM, Ramus SJ, Goode EL, Monteiro ANA, Gayther SA, Narod SA, Pharoah PDP, Sellers TA, Phelan CM (2015)


Publication Type: Journal article

Publication year: 2015

Journal

Book Volume: 39

Pages Range: 689-97

Journal Issue: 8

DOI: 10.1002/gepi.21921

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.

Authors with CRIS profile

Involved external institutions

Oregon Health and Science University (OSHU) US United States (USA) (US) Medizinische Hochschule Hannover (MHH) / Hannover Medical School DE Germany (DE) Glasgow Royal Infirmary (GRI) GB United Kingdom (GB) University of Cambridge GB United Kingdom (GB) University of Kansas (KU) US United States (USA) (US) Danish Cancer Society Research Center DK Denmark (DK) H. Lee Moffitt Cancer Center & Research Institute US United States (USA) (US) Princess Anne Hospital GB United Kingdom (GB) Beatson West of Scotland Cancer Centre (BWSCC) GB United Kingdom (GB) University College London (UCL) GB United Kingdom (GB) University of Southern California (USC) US United States (USA) (US) Radboud University Nijmegen NL Netherlands (NL) University of California Irvine US United States (USA) (US) N.N. Alexandrov National Cancer Centre of Belarus for Oncology and Medical Radiology BY Belarus (BY) Cancer Council Victoria AU Australia (AU) Rutgers Cancer Institute of New Jersey US United States (USA) (US) Memorial Sloan Kettering Cancer Center US United States (USA) (US) Haukeland University Hospital / Haukeland universitetssykehus NO Norway (NO) National Cancer Institute (NCI) US United States (USA) (US) British Columbia Cancer Agency CA Canada (CA) University of Pittsburgh US United States (USA) (US) Helsingin yliopisto / University of Helsinki FI Finland (FI) Peter MacCallum Cancer Centre AU Australia (AU) Deutsches Krebsforschungszentrum (DKFZ) DE Germany (DE) University of New Mexico (UNM) / Universidad de Nuevo México US United States (USA) (US) Brigham and Women's Hospital (BWH) US United States (USA) (US) Mayo Clinic US United States (USA) (US) Pomeranian Medical University / Pomorski Uniwersytet Medyczny w Szczecinie (PMU) PL Poland (PL) Maria Skłodowska-Curie Institute of Oncology / Centrum Onkologii–Instytut im. Marii Skłodowskiej-Curie w Warszawie PL Poland (PL) Kliniken Essen-Mitte DE Germany (DE) Katholieke Universiteit Leuven (KUL) / Catholic University of Leuven BE Belgium (BE) Dartmouth College US United States (USA) (US) Friedrich-Schiller-Universität Jena DE Germany (DE) Shanghai Cancer Institute / 上海市肿瘤研究所 CN China (CN) Cedars-Sinai Medical Center US United States (USA) (US) Ramsay Sime Darby Health Care (RSDHC) MY Malaysia (MY) University of Texas MD Anderson Cancer Center US United States (USA) (US) University of Copenhagen DK Denmark (DK) Aichi Cancer Center Research Institute JP Japan (JP) Duke University US United States (USA) (US) Roswell Park Cancer Institute US United States (USA) (US) Texas Southern University (TSU) US United States (USA) (US) University of Malaya (UM) / Universiti Malaya MY Malaysia (MY) Stanford University US United States (USA) (US) Radboud University Nijmegen Medical Centre / Radboudumc of voluit Radboud Universitair Medisch Centrum (UMC) NL Netherlands (NL) Public Health Ontario CA Canada (CA) Yale University US United States (USA) (US) Princess Margaret Cancer Centre / Princess Margaret Hospital CA Canada (CA) University of Washington US United States (USA) (US) Vanderbilt University US United States (USA) (US) University of Hawaii (U.H.) US United States (USA) (US) The University of Melbourne AU Australia (AU) Institute for Oncology Ljubljana (OIL) SI Slovenia (SI) Medical University of South Carolina (MUSC) US United States (USA) (US) University of Toronto CA Canada (CA)

How to cite

APA:

Amankwah, E.K., Lin, H.-Y., Tyrer, J.P., Lawrenson, K., Dennis, J., Chornokur, G.,... Phelan, C.M. (2015). Epithelial-Mesenchymal Transition (EMT) Gene Variants and Epithelial Ovarian Cancer (EOC) Risk. Genetic Epidemiology, 39(8), 689-97. https://dx.doi.org/10.1002/gepi.21921

MLA:

Amankwah, Ernest K., et al. "Epithelial-Mesenchymal Transition (EMT) Gene Variants and Epithelial Ovarian Cancer (EOC) Risk." Genetic Epidemiology 39.8 (2015): 689-97.

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