PT  - JOURNAL ARTICLE
AU  - Glubb, Dylan M
AU  - Thompson, Deborah J
AU  - Aben, Katja KH
AU  - Alsulimani, Ahmad
AU  - Amant, Frédéric
AU  - Annibali, Daniela
AU  - Attia, John
AU  - Barricarte, Aurelio
AU  - Beckmann, Matthias W.
AU  - Berchuck, Andrew
AU  - Bermisheva, Marina
AU  - Bernardini, Marcus Q.
AU  - Bischof, Katharina
AU  - Bjørge, Line
AU  - Bodelon, Clara
AU  - Brand, Alison H
AU  - Brenton, James D.
AU  - Brinton, Louise A.
AU  - Bruinsma, Fiona
AU  - Buchanan, Daniel D.
AU  - Burghaus, Stefanie
AU  - Bützow, Ralf
AU  - Cai, Hui
AU  - Carney, Michael E.
AU  - Chanock, Stephen J.
AU  - Chen, Chu
AU  - Chen, Xiaoqing
AU  - Chen, Zhihua
AU  - Cook, Linda S.
AU  - Cunningham, Julie M.
AU  - De Vivo, Immaculata
AU  - DeFazio, Anna
AU  - Doherty, Jennifer A.
AU  - Dork, Thilo
AU  - du Bois, Andreas
AU  - Dunning, Alison M
AU  - Durst, Matthias
AU  - Edwards, Todd
AU  - Edwards, Robert P.
AU  - Ekici, Arif B.
AU  - Ewing, Ailith
AU  - Fasching, Peter A.
AU  - Ferguson, Sarah
AU  - Flanagan, James M.
AU  - Fostira, Florentia
AU  - Fountzilas, George
AU  - Friedenreich, Christine M.
AU  - Gao, Bo
AU  - Gaudet, Mia M.
AU  - Gawełko, Jan
AU  - Gentry-Maharaj, Aleksandra
AU  - Giles, Graham G.
AU  - Glasspool, Rosalind
AU  - Goodman, Marc T.
AU  - Gronwald, Jacek
AU  - Harris, Holly R
AU  - Harter, Philipp
AU  - Hein, Alexander
AU  - Heitz, Florian
AU  - Hildebrandt, Michelle A.T.
AU  - Hillemanns, Peter
AU  - Høgdall, Estrid
AU  - Høgdall, Claus K.
AU  - Holliday, Elizabeth G
AU  - Huntsman, David G.
AU  - Huzarski, Tomasz
AU  - Jakubowska, Anna
AU  - Jensen, Allan
AU  - Jones, Michael E.
AU  - Karlan, Beth Y.
AU  - Karnezis, Anthony
AU  - Kelley, Joseph L
AU  - Khusnutdinova, Elza
AU  - Killeen, Jeffrey L.
AU  - Kjaer, Susanne K.
AU  - Klapdor, Rüdiger
AU  - Köbel, Martin
AU  - Konopka, Bozena
AU  - Konstantopoulou, Irene
AU  - Kopperud, Reidun K.
AU  - Koti, Madhuri
AU  - Kraft, Peter
AU  - Kupryjanczyk, Jolanta
AU  - Lambrechts, Diether
AU  - Larson, Melissa C.
AU  - Le Marchand, Loic
AU  - Lele, Shashikant
AU  - Lester, Jenny
AU  - Li, Andrew J
AU  - Liang, Dong
AU  - Liebrich, Clemens
AU  - Lipworth, Loren
AU  - Lissowska, Jolanta
AU  - Lu, Lingeng
AU  - Lu, Karen H.
AU  - Macciotta, Alessandra
AU  - Mattiello, Amalia
AU  - May, Taymaa
AU  - McAlpine, Jessica N.
AU  - McGuire, Valerie
AU  - McNeish, Iain A.
AU  - Menon, Usha
AU  - Modugno, Francesmary
AU  - Moysich, Kirsten B.
AU  - Nevanlinna, Heli
AU  - Odunsi, Kunle
AU  - Olsson, Håkan
AU  - Orsulic, Sandra
AU  - Osorio, Ana
AU  - Palli, Domenico
AU  - Park-Simon, Tjoung-Won
AU  - Pearce, Celeste L.
AU  - Pejovic, Tanja
AU  - Permuth, Jennifer B
AU  - Podgorska, Agnieszka
AU  - Ramus, Susan J.
AU  - Rebbeck, Timothy R.
AU  - Riggan, Marjorie J.
AU  - Risch, Harvey A.
AU  - Rothstein, Joseph H.
AU  - Runnebaum, Ingo B.
AU  - Scott, Rodney J.
AU  - Sellers, Thomas A.
AU  - Senz, Janine
AU  - Setiawan, Veronica Wendy
AU  - Siddiqui, Nadeem
AU  - Sieh, Weiva
AU  - Spiewankiewicz, Beata
AU  - Sutphen, Rebecca
AU  - Swerdlow, Anthony J.
AU  - Szafron, Lukasz Michal
AU  - Teo, Soo Hwang
AU  - Thompson, Pamela J
AU  - Thomsen, Liv Cecilie Vestrheim
AU  - Titus, Linda
AU  - Tone, Alicia
AU  - Tumino, Rosario
AU  - Turman, Constance
AU  - Vanderstichele, Adriaan
AU  - Velez Edwards, Digna
AU  - Vergote, Ignace
AU  - Vierkant, Robert A.
AU  - Wang, Zhaoming
AU  - Wang-Gohrke, Shan
AU  - Webb, Penelope M.
AU  - White, Emily
AU  - Whittemore, Alice S.
AU  - Winham, Stacey J.
AU  - Wu, Xifeng
AU  - Wu, Anna H.
AU  - Yannoukakos, Drakoulis
AU  - Spurdle, Amanda B
AU  - O'Mara, Tracy A
TI  - Cross-cancer genome-wide association study of endometrial cancer and epithelial ovarian cancer identifies genetic risk regions associated with risk of both cancers.
AID  - 10.1158/1055-9965.EPI-20-0739
DP  - 2020 Jan 01
TA  - Cancer Epidemiology Biomarkers & Prevention
PG  - cebp.0739.2020
4099  - http://cebp.aacrjournals.org/content/early/2020/11/03/1055-9965.EPI-20-0739.short
4100  - http://cebp.aacrjournals.org/content/early/2020/11/03/1055-9965.EPI-20-0739.full
AB  - Background: Accumulating evidence suggests a relationship between endometrial cancer and ovarian cancer. Independent genome-wide association studies (GWAS) for endometrial cancer and ovarian cancer have identified 16 and 27 risk regions, respectively, four of which overlap between the two cancers. We aimed to identify joint endometrial and ovarian cancer risk loci by performing a meta-analysis of GWAS summary statistics from these two cancers. Methods: Using LDScore regression, we explored the genetic correlation between endometrial cancer and ovarian cancer. To identify loci associated with the risk of both cancers, we implemented a pipeline of statistical genetic analyses (i.e. inverse-variance meta-analysis, co-localization, and M-values), and performed analyses stratified by subtype. Candidate target genes were then prioritized using functional genomic data. Results: Genetic correlation analysis revealed significant genetic correlation between the two cancers (rG = 0.43, P = 2.66 × 10-5). We found seven loci associated with risk for both cancers (PBonferroni < 2.4 × 10-9). In addition, four novel sub-genome wide regions at 7p22.2, 7q22.1, 9p12 and 11q13.3 were identified (P < 5 × 10-7). Promoter-associated HiChIP chromatin loops from immortalized endometrium and ovarian cell lines, and expression quantitative trait loci (eQTL) data highlighted candidate target genes for further investigation. Conclusion: Using cross-cancer GWAS meta-analysis, we have identified several joint endometrial and ovarian cancer risk loci and candidate target genes for future functional analysis. Impact: Our research highlights the shared genetic relationship between endometrial cancer and ovarian cancer. Further studies in larger sample sets are required to confirm our findings.