Cross-Cancer Genome-Wide Association Study of Endometrial Cancer and Epithelial Ovarian Cancer Identifies Genetic Risk Regions Associated with Risk of Both Cancers

Autor: Ana Osorio, Fiona Bruinsma, Andrew J. Li, Janine Senz, Stacey J. Winham, Michael E. Carney, Deborah J. Thompson, Xifeng Wu, Susan J. Ramus, Alicia A. Tone, Robert P. Edwards, Chu Chen, Daniel D. Buchanan, Rüdiger Klapdor, Diether Lambrechts, Anthony N. Karnezis, Ralf Bützow, Graham G. Giles, Jolanta Kupryjanczyk, James D. Brenton, Pamela J. Thompson, Joseph L. Kelley, Hui Cai, Dylan M. Glubb, Peter Hillemanns, Veronica Wendy Setiawan, Reidun K. Kopperud, Francesmary Modugno, Rodney J. Scott, Karen H. Lu, Andreas du Bois, Weiva Sieh, Clara Bodelon, Katharina Bischof, Sarah E. Ferguson, Ignace Vergote, Todd L. Edwards, Nadeem Siddiqui, Jennifer A. Doherty, Celeste Leigh Pearce, David G. Huntsman, Håkan Olsson, Ailith Ewing, Tjoung-Won Park-Simon, Harvey A. Risch, Taymaa May, Soo Hwang Teo, Elizabeth G. Holliday, Penelope M. Webb, Lukasz Michael Szafron, Alexander Hein, Martin Köbel, Marjorie J. Riggan, Madhuri Koti, Ahmad Alsulimani, Matthias W. Beckmann, Heli Nevanlinna, Domenico Palli, Melissa C. Larson, Emily White, Ingo B. Runnebaum, Robert A. Vierkant, Elza Khusnutdinova, Jolanta Lissowska, Andrew Berchuck, Rosalind Glasspool, Drakoulis Yannoukakos, Alison M. Dunning, Rosario Tumino, Mia M. Gaudet, Alice S. Whittemore, Anna Jakubowska, Marcus Q. Bernardini, Jennifer B. Permuth, Kunle Odunsi, Aleksandra Gentry-Maharaj, Florentia Fostira, Philipp Harter, Rebecca Sutphen, Sandra Orsulic, Beata Spiewankiewicz, Susanne K. Kjaer, Jessica N. McAlpine, Valerie McGuire, Julie M. Cunningham, Jeffrey Killeen, Christine M. Friedenreich, Estrid Høgdall, George Fountzilas, Michelle A.T. Hildebrandt, Katja K.H. Aben, Tomasz Huzarski, Frédéric Amant, Zhaoming Wang, James M. Flanagan, Timothy R. Rebbeck, Joseph H. Rothstein, Clemens Liebrich, Immaculata De Vivo, Linda Titus, Anna deFazio, Jan Gawełko, Irene Konstantopoulou, Adriaan Vanderstichele, Stephen J. Chanock, Jenny Lester, Amanda B. Spurdle, Allan Jensen, Claus Høgdall, Daniela Annibali, Amalia Mattiello, Peter Kraft, Loic Le Marchand, Line Bjørge, Marina Bermisheva, Agnieszka Podgorska, John Attia, Tracy A. O'Mara, Shashikant Lele, Thomas A. Sellers, Bo Gao, Holly R. Harris, Shan Wang-Gohrke, Lingeng Lu, Louise A. Brinton, Alessandra Macciotta, Digna R. Velez Edwards, Peter A. Fasching, Marc T. Goodman, Linda S. Cook, Constance Turman, Jacek Gronwald, Liv Cecilie Vestrheim Thomsen, Matthias Dürst, Kirsten B. Moysich, Usha Menon, Dong Liang, Arif B. Ekici, Bozena Konopka, Aurelio Barricarte, Thilo Dörk, Stefanie Burghaus, Michael Jones, Loren Lipworth, Zhihua Chen, Xiaoqing Chen, Alison Brand, Iain A. McNeish, Tanja Pejovic, Florian Heitz, Beth Y. Karlan, Anthony J. Swerdlow, Anna H. Wu
Přispěvatelé: Obstetrics and Gynaecology, CCA - Cancer biology and immunology, Amsterdam Reproduction & Development (AR&D)
Rok vydání: 2021
Předmět:
Zdroj: Cancer Epidemiology, Biomarkers & Prevention, 30, 1, pp. 217-228
Cancer Epidemiology, Biomarkers & Prevention, 30, 217-228
Cancer epidemiology, biomarkers & prevention, 30(1), 217-228. American Association for Cancer Research Inc.
Glubb, D M, Thompson, D J, Aben, K K, Alsulimani, A, Amant, F, Annibali, D, Attia, J, Barricarte, A, Beckmann, M W, Berchuck, A, Bermisheva, M, Bernardini, M Q, Bischof, K, Bjørge, L, Bodelon, C, Brand, A H, Brenton, J D, Brinton, L A, Bruinsma, F, Buchanan, D D, Burghaus, S, Bützow, R, Cai, H, Carney, M E, Chanock, S J, Chen, C, Chen, X, Chen, Z, Cook, L S, Cunningham, J M, De Vivo, I, Defazio, A, Doherty, J A, Dork, T, Du Bois, A, Dunning, A M, Durst, M, Edwards, T, Edwards, R P, Ekici, A B, Ewing, A, Fasching, P A, Ferguson, S, Flanagan, J M, Fostira, F, Fountzilas, G, Friedenreich, C M, Gao, B, Gaudet, M M, Gawełko, J, Gentry-maharaj, A, Giles, G G, Glasspool, R, Goodman, M T, Gronwald, J, Harris, H R, Harter, P, Hein, A, Heitz, F, Hildebrandt, M A T, Hillemanns, P, Høgdall, E, Høgdall, C K, Holliday, E G, Huntsman, D G, Huzarski, T, Jakubowska, A, Jensen, A, Jones, M E, Karlan, B Y, Karnezis, A, Kelley, J L, Khusnutdinova, E, Killeen, J L, Kjaer, S K, Klapdor, R, Köbel, M, Konopka, B, Konstantopoulou, I, Kopperud, R K, Koti, M, Kraft, P, Kupryjanczyk, J, Lambrechts, D, Larson, M C, Le Marchand, L, Lele, S, Lester, J, Li, A J, Liang, D, Liebrich, C, Lipworth, L, Lissowska, J, Lu, L, Lu, K H, Macciotta, A, Mattiello, A, May, T, Mcalpine, J N, Mcguire, V, Mcneish, I A, Menon, U, Modugno, F, Moysich, K B, Nevanlinna, H, Odunsi, K, Olsson, H, Orsulic, S, Osorio, A, Palli, D, Park-simon, T, Pearce, C L, Pejovic, T, Permuth, J B, Podgorska, A, Ramus, S J, Rebbeck, T R, Riggan, M J, Risch, H A, Rothstein, J H, Runnebaum, I B, Scott, R J, Sellers, T A, Senz, J, Setiawan, V W, Siddiqui, N, Sieh, W, Spiewankiewicz, B, Sutphen, R, Swerdlow, A J, Szafron, L M, Teo, S H, Thompson, P J, Thomsen, L C V, Titus, L, Tone, A, Tumino, R, Turman, C, Vanderstichele, A, Velez Edwards, D, Vergote, I, Vierkant, R A, Wang, Z, Wang-gohrke, S, Webb, P M, White, E, Whittemore, A S, Winham, S J, Wu, X, Wu, A H, Yannoukakos, D, Spurdle, A B & O'mara, T A 2021, ' Cross-cancer genome-wide association study of endometrial cancer and epithelial ovarian cancer identifies genetic risk regions associated with risk of both cancers. ', Cancer Epidemiology, Biomarkers & Prevention, vol. 30, no. 1, cebp.0739.2020, pp. 217-228 . https://doi.org/10.1158/1055-9965.EPI-20-0739
ISSN: 1055-9965
Popis: 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, colocalization, 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 subgenome-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 data highlighted candidate target genes for further investigation. Conclusions: 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.
Databáze: OpenAIRE
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