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Identification of nine new susceptibility loci for endometrial cancer

Endometrial cancer is the most commonly diagnosed cancer of the female reproductive tract in developed countries. Through genome-wide association studies (GWAS), we have previously identified eight risk loci for endometrial cancer. Here, we present an expanded meta-analysis of 12,906 endometrial can...

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Main Authors: Glubb, Dylan M, Amant, Frédéric, Annibali, Daniela, Ashton, Katie, Attia, John, Auer, Paul L, Beckmann, Matthias W, Black, Amanda, Bolla, Manjeet K, Brauch, Hiltrud, Brenner, Hermann, Buchanan, Daniel D, Burwinkel, Barbara, Chang-Claude, Jenny, Chanock, Stephen J, Chen, Chu, Chen, Maxine M, Cheng, Timothy H.T, Clendenning, Mark, Couch, Fergus J, Cox, Angela, Crous-Bous, Marta, Czene, Kamila, Depreeuw, Jeroen, Doherty, Jennifer Anne, Dörk, Thilo, Dürst, Matthias, Ekici, Arif B, Fasching, Peter A, Fridley, Brooke L, Friedenreich, Christine M, García-Closas, Montserrat, Gaudet, Mia M, Giles, Graham G, Goode, Ellen L, Gorman, Maggie, Haiman, Christopher A, Hall, Per, Hankison, Susan E, Healey, Catherine S, Hein, Alexander, Hillemanns, Peter, Hodgson, Shirley, Høivik, Erling Andre, Holliday, Elizabeth G, Hopper, John L, Jones, Angela, Kristensen, Vessela N, Lambrechts, Diether, Marchand, Loic Le, Lindblom, Annika, Lissowska, Jolanta, Lu, Lingeng, Magliocco, Anthony M, Martin, Lynn, McEvoy, Mark, Meindl, Alfons, Michailidou, Kyriaki, Milne, Roger L, Mints, Miriam, Montgomery, Grant W, Nassir, Rami, Olsson, Håkan, Otton, Geoffrey, Palles, Claire, Peto, Julian, Pooler, Loreall, Prescott, Jennifer, Rebbeck, Timothy R, Risch, Harvey A, Rogers, Peter A.W, Rübner, Matthias, Runnebaum, Ingo, Sacerdote, Carlotta, Sarto, Gloria E, Schumacher, Fredrick, Scott, Rodney J, Setiawan, V. Wendy, Shah, Mitul, Sheng, Xin, Shu, Xiao-Ou, Tham, Emma, Trovik, Jone, Turman, Constance, Tyrer, Jonathan P, Vachon, Celine, VanDen Berg, David, Vanderstichele, Adriaan, Wang, Zhaoming, Winham, Stacey J, Wolk, Alicja, Xia, Lucy, Yang, Hannah P, Yu, Herbert, Zheng, Wei, Pharoah, Paul D.P, Kraft, Peter, Tomlinson, Ian, Easton, Douglas F, Thompson, Deborah J
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Language:English
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Summary:Endometrial cancer is the most commonly diagnosed cancer of the female reproductive tract in developed countries. Through genome-wide association studies (GWAS), we have previously identified eight risk loci for endometrial cancer. Here, we present an expanded meta-analysis of 12,906 endometrial cancer cases and 108,979 controls (including new genotype data for 5624 cases) and identify nine novel genome-wide significant loci, including a locus on 12q24.12 previously identified by meta-GWAS of endometrial and colorectal cancer. At five loci, expression quantitative trait locus (eQTL) analyses identify candidate causal genes; risk alleles at two of these loci associate with decreased expression of genes, which encode negative regulators of oncogenic signal transduction proteins (SH2B3 (12q24.12) and NF1 (17q11.2)). In summary, this study has doubled the number of known endometrial cancer risk loci and revealed candidate causal genes for future study.