Epithelial‐Mesenchymal Transition (EMT) Gene Variants and Epithelial Ovarian Cancer (EOC) Risk
Authors: Amankwah Ernest K. , Lin Hui‐Yi , Tyrer Jonathan P. , Lawrenson Kate , Dennis Joe , Chornokur Ganna , Aben Katja K. H. , Anton‐Culver Hoda , Antonenkova Natalia , Bruinsma Fiona , Bandera Elisa V. , Bean Yukie T. , Beckmann Matthias W. , Bisogna Maria , Bjorge Line , Bogdanova Natalia , Brinton Louise A. , Brooks‐Wilson Angela , Bunker Clareann H. , Butzow Ralf , Campbell Ian G. , Carty Karen , Chen Zhihua , Chen Y. Ann , Chang‐Claude Jenny , Cook Linda S. , Cramer Daniel W. , Cunningham Julie M. , Cybulski Cezary , Dansonka‐Mieszkowska Agnieszka , du Bois Andreas , Despierre Evelyn , Dicks Ed , Doherty Jennifer A. , Dörk Thilo , Dürst Matthias , Easton Douglas F. , Eccles Diana M. , Edwards Robert P. , Ekici Arif B. , Fasching Peter A. , Fridley Brooke L. , Gao Yu‐Tang , Gentry‐Maharaj Aleksandra , Giles Graham G. , Glasspool Rosalind , Goodman Marc T. , Gronwald Jacek , Harrington Patricia , Harter Philipp , Hasmad Hanis N. , Hein Alexander , Heitz Florian , Hildebrandt Michelle A. T. , Hillemanns Peter , Hogdall Claus K. , Hogdall Estrid , Hosono Satoyo , Iversen Edwin S. , Jakubowska Anna , Jensen Allan , Ji Bu‐Tian , Karlan Beth Y. , Jim Heather , Kellar Melissa , Kiemeney Lambertus A. , Krakstad Camilla , Kjaer Susanne K. , Kupryjanczyk Jolanta , Lambrechts Diether , Lambrechts Sandrina , Le Nhu D. , Lee Alice W. , Lele Shashi , Leminen Arto , Lester Jenny , Levine Douglas A. , Liang Dong , Lim Boon Kiong , Lissowska Jolanta , Lu Karen , Lubinski Jan , Lundvall Lene , Massuger Leon F. A. G. , Matsuo Keitaro , McGuire Valerie , McLaughlin John R. , McNeish Ian , Menon Usha , Milne Roger L. , Modugno Francesmary , Moysich Kirsten B. , Ness Roberta B. , Nevanlinna Heli , Eilber Ursula , Odunsi Kunle , Olson Sara H. , Orlow Irene , Orsulic Sandra , Weber Rachel Palmieri , Paul James , Pearce Celeste L. , Pejovic Tanja , Pelttari Liisa M. , Permuth‐Wey Jennifer , Pike Malcolm C. , Poole Elizabeth M. , Risch Harvey A. , Rosen Barry , Rossing Mary Anne , Rothstein Joseph H. , Rudolph Anja , Runnebaum Ingo B. , Rzepecka Iwona K. , Salvesen Helga B. , Schernhammer Eva , Schwaab Ira , Shu Xiao‐Ou , Shvetsov Yurii B. , Siddiqui Nadeem , Sieh Weiva , Song Honglin , Southey Melissa C. , Spiewankiewicz Beata , Sucheston‐Campbell Lara , Teo Soo‐Hwang , Terry Kathryn L. , Thompson Pamela J. , Thomsen Lotte , Tangen Ingvild L. , Tworoger Shelley S. , van Altena Anne M. , Vierkant Robert A. , Vergote Ignace , Walsh Christine S. , Wang‐Gohrke Shan , Wentzensen Nicolas , Whittemore Alice S. , Wicklund Kristine G. , Wilkens Lynne R. , Wu Anna H. , Wu Xifeng , Woo Yin‐Ling , Yang Hannah , Zheng Wei , Ziogas Argyrios , Kelemen Linda E. , Berchuck Andrew ,   Georgia Chenevix‐Trench on behalf of the AOCS management group, Schildkraut Joellen M. , Ramus Susan J. , Goode Ellen L. , Monteiro Alvaro N. A. , Gayther Simon A. , Narod Steven A. , Pharoah Paul D. P. , Sellers Thomas A. , Phelan Catherine M. 
Published: September 2015

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.