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

Authors:
Ernest K Amankwah Hui-Yi Lin Jonathan P Tyrer Kate Lawrenson Joe Dennis Ganna Chornokur Katja K H Aben Hoda Anton-Culver Natalia Antonenkova Fiona Bruinsma Elisa V Bandera Yukie T Bean Matthias W Beckmann Maria Bisogna Line Bjorge Natalia Bogdanova Louise A Brinton Angela Brooks-Wilson Clareann H Bunker Ralf Butzow Ian G Campbell Karen Carty Zhihua Chen Y Ann Chen Jenny Chang-Claude Linda S Cook Daniel W Cramer Julie M Cunningham Cezary Cybulski Agnieszka Dansonka-Mieszkowska Andreas du Bois Evelyn Despierre Ed Dicks Jennifer A Doherty Thilo Dörk Matthias Dürst Douglas F Easton Diana M Eccles Robert P Edwards Arif B Ekici Peter A Fasching Brooke L Fridley Yu-Tang Gao Aleksandra Gentry-Maharaj Graham G Giles Rosalind Glasspool Marc T Goodman Jacek Gronwald Patricia Harrington Philipp Harter Hanis N Hasmad Alexander Hein Florian Heitz Michelle A T Hildebrandt Peter Hillemanns Claus K Hogdall Estrid Hogdall Satoyo Hosono Edwin S Iversen Anna Jakubowska Allan Jensen Bu-Tian Ji Beth Y Karlan Heather Jim Melissa Kellar Lambertus A Kiemeney Camilla Krakstad Susanne K Kjaer Jolanta Kupryjanczyk Diether Lambrechts Sandrina Lambrechts Nhu D Le Alice W Lee Shashi Lele Arto Leminen Jenny Lester Douglas A Levine Dong Liang Boon Kiong Lim Jolanta Lissowska Karen Lu Jan Lubinski Lene Lundvall Leon F A G Massuger Keitaro Matsuo Valerie McGuire John R McLaughlin Ian McNeish Usha Menon Roger L Milne Francesmary Modugno Kirsten B Moysich Roberta B Ness Heli Nevanlinna Ursula Eilber Kunle Odunsi Sara H Olson Irene Orlow Sandra Orsulic Rachel Palmieri Weber James Paul Celeste L Pearce Tanja Pejovic Liisa M Pelttari Jennifer Permuth-Wey Malcolm C Pike Elizabeth M Poole Harvey A Risch Barry Rosen Mary Anne Rossing Joseph H Rothstein Anja Rudolph Ingo B Runnebaum Iwona K Rzepecka Helga B Salvesen Eva Schernhammer Ira Schwaab Xiao-Ou Shu Yurii B Shvetsov Nadeem Siddiqui Weiva Sieh Honglin Song Melissa C Southey Beata Spiewankiewicz Lara Sucheston-Campbell Soo-Hwang Teo Kathryn L Terry Pamela J Thompson Lotte Thomsen Ingvild L Tangen Shelley S Tworoger Anne M van Altena Robert A Vierkant Ignace Vergote Christine S Walsh Shan Wang-Gohrke Nicolas Wentzensen Alice S Whittemore Kristine G Wicklund Lynne R Wilkens Anna H Wu Xifeng Wu Yin-Ling Woo Hannah Yang Wei Zheng Argyrios Ziogas Linda E Kelemen Andrew Berchuck Joellen M Schildkraut Susan J Ramus Ellen L Goode Alvaro N A Monteiro Simon A Gayther Steven A Narod Paul D P Pharoah Thomas A Sellers Catherine M Phelan

Genet Epidemiol 2015 Dec 24;39(8):689-97. Epub 2015 Sep 24.

Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, Florida, United States of America.

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.

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Source
http://dx.doi.org/10.1002/gepi.21921DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4721602PMC
December 2015
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