Identification of nine new susceptibility loci for endometrial cancer

Tracy A. O’Mara, Dylan M. Glubb, Frederic Amant, Daniela Annibali, Katie Ashton, John Attia, Paul L. Auer, Matthias W. Beckmann, Amanda Black, Manjeet K. Bolla, Hiltrud Brauch, Hermann Brenner, Louise Brinton, Daniel D. Buchanan, Barbara Burwinkel, Jenny Chang-Claude, Stephen J. Chanock, Chu Chen, Maxine M. Chen, Timothy H.T. ChengChristine L. Clarke, Mark Clendenning, Linda S. Cook, Fergus J. Couch, Angela Cox, Marta Crous-Bous, Kamila Czene, Felix Day, Joe Dennis, Jeroen Depreeuw, Jennifer Anne Doherty, Thilo Dörk, Sean C. Dowdy, Matthias Dürst, Arif B. Ekici, Peter A. Fasching, Brooke L. Fridley, Christine M. Friedenreich, Lin Fritschi, Jenny Fung, Montserrat García-Closas, Mia M. Gaudet, Graham G. Giles, Ellen L. Goode, Maggie Gorman, Christopher A. Haiman, Per Hall, Susan E. Hankison, Catherine S. Healey, Alexander Hein, Peter Hillemanns, Shirley Hodgson, Erling A. Hoivik, Elizabeth G. Holliday, John L. Hopper, David J. Hunter, Angela Jones, Camilla Krakstad, Vessela N. Kristensen, Diether Lambrechts, Loic Le Marchand, Xiaolin Liang, Annika Lindblom, Jolanta Lissowska, Jirong Long, Lingeng Lu, Anthony M. Magliocco, Lynn Martin, Mark McEvoy, Alfons Meindl, Kyriaki Michailidou, Roger L. Milne, Miriam Mints, Grant W. Montgomery, Rami Nassir, Håkan Olsson, Irene Orlow, Geoffrey Otton, Claire Palles, John R.B. Perry, Julian Peto, Loreall Pooler, Jennifer Prescott, Tony Proietto, Timothy R. Rebbeck, Harvey A. Risch, Peter A.W. Rogers, Matthias Rübner, Ingo Runnebaum, Carlotta Sacerdote, Gloria E. Sarto, Fredrick Schumacher, Rodney J. Scott, V. Wendy Setiawan, Mitul Shah, Xin Sheng, Xiao Ou Shu, Melissa C. Southey, Anthony J. Swerdlow, Emma Tham, Jone Trovik, Constance Turman, Jonathan P. Tyrer, Celine Vachon, David VanDen Berg, Adriaan Vanderstichele, Zhaoming Wang, Penelope M. Webb, Nicolas Wentzensen, Henrica M.J. Werner, Stacey J. Winham, Alicja Wolk, Lucy Xia, Yong Bing Xiang, Hannah P. Yang, Herbert Yu, Wei Zheng, Paul D.P. Pharoah, Alison M. Dunning, Peter Kraft, Immaculata De Vivo, Ian Tomlinson, Douglas F. Easton, Amanda B. Spurdle, Deborah J. Thompson

Research output: Contribution to journalArticle

20 Scopus citations

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.

Original languageEnglish (US)
Article number3166
JournalNature communications
Volume9
Issue number1
DOIs
StatePublished - Dec 1 2018

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Fingerprint Dive into the research topics of 'Identification of nine new susceptibility loci for endometrial cancer'. Together they form a unique fingerprint.

  • Cite this

    O’Mara, T. A., Glubb, D. M., Amant, F., Annibali, D., Ashton, K., Attia, J., Auer, P. L., Beckmann, M. W., Black, A., Bolla, M. K., Brauch, H., Brenner, H., Brinton, L., Buchanan, D. D., Burwinkel, B., Chang-Claude, J., Chanock, S. J., Chen, C., Chen, M. M., ... Thompson, D. J. (2018). Identification of nine new susceptibility loci for endometrial cancer. Nature communications, 9(1), [3166]. https://doi.org/10.1038/s41467-018-05427-7