Identification of nine new susceptibility loci for endometrial cancer.

Tracy A. O’Mara, Dylan M. Glubb, Amant F, Daniela Annibali, Ashton K, John Attia, Auer PL, Beckmann MW, Black A, Bolla MK, Hiltrud Brauch, Hermann Brenner, Brinton L, Daniel D. Buchanan, Burwinkel B, Chang-Claude J, Chanock SJ, Chen C, Chen MM, Cheng THT, Clarke CL, Clendenning M, Cook LS, Couch FJ, Angela Cox, Crous-Bous M, Czene K, Felix R. Day, Joe Dennis, Depreeuw J, Doherty JA, Thilo Dörk, Dowdy SC, Dürst M, Arif B. Ekici, Peter A. Fasching, Fridley BL, Friedenreich CM, Fritschi L, Fung J, Garcia-Closas M, Gaudet MM, Giles GG, Goode EL, Gorman M, Haiman CA, Hall P, Hankison SE, Healey CS, Alexander Hein, Peter Hillemanns, Hodgson S, Erling A. Høivik, Holliday EG, Hopper JL, Hunter DJ, Jones A, Camilla Krakstad, Kristensen VN, Diether Lambrechts, Marchand LL, Liang X, Annika Lindblom, Jolanta Lissowska, Jirong Long, Lu L, Magliocco AM, Lynn Martin, Mark McEvoy, Meindl A, Kyriaki Michailidou, Roger L Milne, Mints M, Grant W. Montgomery, Nassir R, Olsson H, Orlow I, Otton G, Palles C, Perry JRB, Peto J, Pooler L, Prescott J, Proietto T, Rebbeck TR, Risch HA, Peter A. W. Rogers, Rübner M, Runnebaum I, Sacerdote C, Sarto GE, Schumacher FR, Scott RJ, Setiawan VW, Shah M, Sheng X, Shu XO, Southey MC, Anthony J. Swerdlow, Emma Tham, Trovik J, Turman C, Tyrer JP, Vachon C, VanDen Berg D, Vanderstichele A, Wang Z, Penelope M. Webb, Wentzensen N, Henrica M.J. Werner, Winham SJ, Alicja Wolk, Xia L, Xiang YB, Yang HP, Yu H, Zheng W, Wei Zheng, Paul D.P. Pharoah, Dunning AM, Peter Kraft, Immaculata De Vivo, Ian Tomlinson, Douglas F. Easton, Spurdle AB, Deborah J. Thompson
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Abstract

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.

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License: CC-BY-4.0