Citations 2
Epithelial‐Mesenchymal Transition (EMT) Gene Variants and Epithelial Ovarian Cancer (EOC) Risk
Amankwah, Ernest K. , Lin, Hui‐Yi , Lawrenson, Kate , Chornokur, Ganna , Aben, Katja K.H. , Antonenkova, Natalia, Bruinsma, Fiona , Bean, Yukie T., Beckmann, Matthias W. , Bisogna, Maria, Bogdanova, Natalia , Brinton, Louise A. , Campbell, Ian , Chen, Zhihua , Chen, Y. Ann , Chang‐Claude, Jenny, Cunningham, Julie M. , Dansonka‐Mieszkowska, Agnieszka , Despierre, Evelyn, Dicks, Ed , Dörk, Thilo , Easton, Douglas F. , Eccles, Diana M., Edwards, Robert P., Ekici, Arif B. , Fasching, Peter A. , Gao, Yu‐Tang , Giles, Graham G. , Glasspool, Rosalind , Goodman, Marc T. , Harrington, Patricia, Harter, Philipp , Hasmad, Hanis Nazihah, Hein, Alexander , Heitz, Florian , Hildebrandt, Michelle A.T., Hillemanns, Peter , Høgdall, Claus , Høgdall, Estrid , Hosono, Satoyo , Iversen, Edwin S., Jakubowska, Anna , Jensen, Allan , Ji, Bu‐Tian , Kellar, Melissa, Kiemeney, Lambertus A. , Krakstad, Camilla , Kupryjańczyk, 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, Lubiński, Jan , Lundvall, Lene, Massuger, Leon F.A.G. , Matsuo, Keitaro , McGuire, Valerie , McLaughlin, John R., McNeish, Iain A. , Menon, Usha , Moysich, Kirsten B., Ness, Roberta B., Eilber, Ursula, Odunsi, Kunle , Olson, Sara H. , Orlow, Irene , Oršulić, Sandra , Weber, Rachel Palmieri , Pearce, Celeste Leigh, Pelttari, Liisa M. , Permuth‐Wey, Jennifer, Pike, Malcolm C., Rossing, Mary Anne, Rothstein, Joseph H. , Runnebaum, Ingo B. , Rzepecka, Iwona K. , Salvesen, Helga B., Schernhammer, Eva , Schwaab, Ira, Shu, Xiao‐Ou, Shvetsov, Yurii B. , Sieh, Weiva , Song, Honglin , Southey, Melissa C. , Śpiewankiewicz, Beata, Sucheston‐Campbell, Lara, Teo, Soo‐Hwang , Terry, Kathryn L. , Thompson, Pamela J., Tangen, Ingvild L. , Tworoger, Shelley S. , Altena, Anne M. van , Vierkant, Robert A. , Vergote, Ignace , Walsh, Christine , Wang‐Gohrke, Shan , Wentzensen, Nicolas, Whittemore, Alice S. , Wicklund, Kristine G. , Wu, Anna H. , Wu, Xifeng , Woo, Yin Ling , Zheng, Wei , Kelemen, Linda E. , group, Georgia Chenevix‐Trench on behalf of the AOCS management, Schildkraut, Joellen M. , Ramus, Susan J. , Goode, Ellen L. , Monteiro, Álvaro N.A. , Gayther, Simon A. , Narod, Steven A., Sellers, Thomas A. , Phelan, Catherine M., Lu, Karen H. , Eccles, Diana , Lambrechts, Diether , Tyrer, Jonathan P. , Dennis, Joe , Anton‐Culver, Hoda , Bandera, Elisa V. , Bjørge, Line , Brooks‐Wilson, Angela , Bunker, Clareann H. , Bützow, Ralf C. , Carty, Karen , Cook, Linda S. , Cramer, Daniel W. , Cybulski, Cezary , Bois, Andreas du , Doherty, Jennifer A. , Dürst, Matthias , Eccles, Diana M., Fridley, Brooke L. , Gentry‐Maharaj, Aleksandra , Gronwald, Jacek , Hildebrandt, Michelle A.T. , Karlan, Beth Y. , Jim, Heather , Kjær, Susanne K. , Lu, Karen, McLaughlin, John R., Milne, Roger L. , Modugno, Francesmary , Nevanlinna, Heli , Paul, James , Pejovic, Tanja B. , Poole, Elizabeth M. , Risch, Harvey A. , Rosen, Barry P. , Rudolph, Anja , Siddiqui, Nadeem , Thomsen, Lotte Nedergaard , Wentzensen, Nicolas , Wilkens, Lynne R. , Yang, Hannah , Ziogas, Argyrios , Berchuck, Andrew , group, Georgia Chenevix‐Trench on behalf of the AOCS management, Pharoah, Paul D.P. , Pelttari, L M , Dörk, Thilo , Lambrechts, Diether , Giles, Graham G , Kiemeney, Lambertus A , McNeish, Iain A , Ramus, Susan J , Teo, Soo H , Tworoger, Shelley S , Hein, Alexander , Hillemanns, Peter , Jensen, Allan , Vierkant, Robert A , Eccles, Diana , Menon, Usha , Lawrenson, Kate , Monteiro, Alvaro N , Moysich, Kirsten , Orlow, Irene , Lissowska, Jolanta , Campbell, Ian G , Southey, Melissa C , Glasspool, Rosalind , Lin, Hui-Yi , Matsuo, Keitaro , Heitz, Florian , Jakubowska, Anna , Kupryjanczyk, Jolanta , Lambrechts, Diether , Sieh, Weiva , Ekici, Arif B , Bogdanova, Natalia V , Zheng, Wei , Høgdall, Estrid , Høgdall, Claus K , Lubinski, Jan , Goodman, Marc T
Genetic Epidemiology | September 24, 2015 | Volume: 39 | Issue: 8 | Pages: 689-697
ABSTRACTEpithelial‐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.
Biomarker-Based Ovarian Carcinoma Typing: A Histologic Investigation in the Ovarian Tumor Tissue Analysis Consortium
Köbel, Martin , Lee, Sandra , Kelemen, Linda E. , Prentice, Leah , Kalli, Kimberly R., Visscher, Daniel W., Keeney, Gary L., Vierkant, Robert A. , Cunningham, Julie M. , Ness, Roberta B., Moysich, Kirsten B., Wozniak, Eva , Gayther, Simon A. , Menon, Usha , Gilks, C. Blake, Huntsman, David G. , Ramus, Susan J. , Goode, Ellen L. , Kalloger, Steve E. , Duggan, Máire A. , Fridley, Brooke L. , Chow, Christine S. , Edwards, Todd , Modugno, Francesmary , Bunker, Clareann H. , Benjamin, Elizabeth , Gentry‐Maharaj, Aleksandra , Ramus, Susan J , Köbel, Martin , Vierkant, Robert A , Menon, Usha , Moysich, Kirsten
Cancer Epidemiology, Biomarkers & Prevention | July 24, 2013 | Volume: 22 | Issue: 10 | Pages: 1677-1686
Abstract Background: Ovarian carcinoma is composed of five major histologic types, which associate with outcome and predict therapeutic response. Our aim was to evaluate histologic type assessments across the centers participating in the Ovarian Tumor Tissue Analysis (OTTA) consortium using an immunohistochemical (IHC) prediction model. Methods: Tissue microarrays (TMA) and clinical data were available for 524 pathologically confirmed ovarian carcinomas. Centralized IHC was conducted for ARID1A, CDKN2A, DKK1, HNF1B, MDM2, PGR, TP53, TFF3, VIM, and WT1, and three histologic type assessments were compared: the original pathologic type, an IHC-based calculated type (termed TB_COSPv2), and a WT1-assisted TMA core review. Results: The concordance between TB_COSPv2 type and original type was 73%. Applying WT1-assisted core review, the remaining 27% discordant cases subdivided into unclassifiable (6%), TB_COSPv2 error (6%), and original type error (15%). The largest discordant subgroup was classified as endometrioid carcinoma by original type and as high-grade serous carcinoma (HGSC) by TB_COSPv2. When TB_COSPv2 classification was used, the difference in overall survival of endometrioid carcinoma compared with HGSC became significant [RR 0.60; 95% confidence interval (CI), 0.37–0.93; P = 0.021], consistent with previous reports. In addition, 71 cases with unclear original type could be histologically classified by TB_COSPv2. Conclusions: Research cohorts, particularly those across different centers within consortia, show significant variability in original histologic type diagnosis. Our IHC-based reclassification produced more homogeneous types with respect to outcome than original type. Impact: Biomarker-based classification of ovarian carcinomas is feasible, improves comparability of results across research studies, and can reclassify cases which lack reliable original pathology. Cancer Epidemiol Biomarkers Prev; 22(10); 1677–86. ©2013 AACR.