Citations 2
Cross-Cancer Genome-Wide Association Study of Endometrial Cancer and Epithelial Ovarian Cancer Identifies Genetic Risk Regions Associated with Risk of Both Cancers
Glubb, Dylan M. , Thompson, Deborah J. , Aben, Katja K.H. , Alsulimani, Ahmad , Amant, Frédéric , Annibali, Daniela , Barricarte, Aurelio , Beckmann, Matthias W. , Bermisheva, Marina , Bernardini, Marcus Q. , Bischof, Katharina , Bodelón, Clara , Brand, Alison H. , Brinton, Louise A. , Bruinsma, Fiona , Burghaus, Stefanie , Cai, Hui , Carney, Michael E. , Chen, Chu , Chen, Xiao Qing, Chen, Zhihua , Cunningham, Julie M. , Vivo, Immaculata De , Dörk, Thilo , Edwards, Todd, Ekici, Arif B. , Ewing, Ailith , Fasching, Peter A. , Ferguson, Sarah, Flanagan, James M. , Fostira, Florentia, Gao, Bo , Gaudet, Mia M. , Gawełko, Jan , Goodman, Marc T. , Harter, Philipp , Hein, Alexander , Hildebrandt, Michelle A.T., Hillemanns, Peter , Høgdall, Claus , Holliday, Elizabeth , Huntsman, David G. , Huzarski, Tomasz , Jones, Michael E. , Kelley, Joseph L., Killeen, Jeffrey , Klapdor, Rüdiger , Köbel, Martin , Konopka, Bożena , Konstantopoulou, Irene , Kopperud, Reidun Kristin, Koti, Madhuri , Lambrechts, Diether , Lele, Shashikant , Lester, Jenny, Li, Andrew J., Liang, Dong , Liebrich, Clemens, Lipworth, Loren , Lissowska, Jolanta , Lu, Karen H., May, Taymaa, McGuire, Valerie , McNeish, Iain A. , Menon, Usha , Moysich, Kirsten B. , Odunsi, Kunle , Olsson, Håkan , Oršulić, Sandra , Osório, Ana , Park‐Simon, Tjoung‐Won , Pearce, Celeste Leigh, Podgórska, Agnieszka , Ramus, Susan J. , Riggan, Marjorie J. , Rothstein, Joseph H. , Runnebaum, Ingo B. , Scott, Rodney J. , Sellers, Thomas A. , Sieh, Weiva , Śpiewankiewicz, Beata, Sutphen, Rebecca , Teo, Soo‐Hwang , Thompson, Pamela J., Titus, Linda , Tone, Alicia , Edwards, Digna Velez, Vergote, Ignace , Wang, Zhaoming , Wang‐Gohrke, Shan , Group, for the OPAL Study, Group, for the AOCS, Whittemore, Alice S. , Wu, Xifeng , Wu, Anna H. , O’Mara, Tracy A. , Lu, Karen H. , Lambrechts, Diether , Barricarte, Aurelio , Bischof, Katharina , Bodelon, Clara , Brenton, James D , Brinton, Louise A , Buchanan, Daniel D , Cunningham, Julie M , De Vivo, Immaculata , Fazio, Anna de , Doherty, Jennifer A , Dörk, Thilo , Dunning, Alison M , Edwards, Todd , Ewing, Ailith , Fasching, Peter A , Flanagan, James M , Friedenreich, Christine M , Gaudet, Mia M , Gawełko, Jan , Gentry‐Maharaj, Aleksandra , Giles, Graham G , Glasspool, Rosalind , Harris, Holly R , Hein, Alexander , Heitz, Florian , Hillemanns, Peter , Jakubowska, Anna , Jones, Michael E , Karlan, Beth Y , Karnezis, Anthony , Kjaer, Susanne K , Klapdor, Rüdiger , Köbel, Martin , Konstantopoulou, Irene , Kupryjanczyk, Jolanta , Lambrechts, Diether , Lissowska, Jolanta , Lu, Lingeng , McAlpine, Jessica N , McNeish, Iain A , Menon, Usha , Nevanlinna, H , Orsulic, Sandra , Palli, Domenico , Park-Simon, Tjoung-Won , Permuth, Jennifer B , Ramus, Susan J , Runnebaum, Ingo B , Sieh, Weiva , Swerdlow, Anthony J , Szafron, Lukasz M , Teo, Soo H , Thompson, Pamela J , Thomsen, Liv Cecilie Vestrheim , Titus, Linda , Tumino, Rosario , Vanderstichele, Adriaan , Vergote, Ignace , Vierkant, Robert A , Webb, Penelope M , Winham, Stacey J , Spurdle, Amanda B , Lambrechts, Diether , Moysich, Kirsten , Wang, Zhaoming , O'Mara, Tracy A , Ekici, Arif B , Amant, Frederic , Høgdall, Claus K , Huzarski, Tomasz , Brand, Alison H , Goodman, Marc T , Attia, John , Berchuck, Andrew , Bjørge, Line , Brenton, James D. , Buchanan, Daniel D. , Bützow, Ralf C. , Chanock, Stephen Jacob , Chen, Xiao Qing, Cook, Linda S. , DeFazio, Anna , Doherty, Jennifer A. , Bois, Andreas du , Dunning, Alison M. , Dürst, Matthias , Fountzilas, George , Giles, Graham G. , Glasspool, Rosalind , Gronwald, Jacek , Harris, Holly R. , Heitz, Florian , Hildebrandt, Michelle A.T. , Høgdall, Estrid , Jakubowska, Anna , Jensen, Allan , Karlan, Beth Y. , Karnezis, Anthony N. , Хуснутдинова, Э. К. , Kjær, Susanne K. , Kraft, Peter , Kupryjańczyk, Jolanta , Larson, Melissa C. , Marchand, Loı̈c Le , Macciotta, Alessandra , Mattiello, Amalia , McAlpine, Jessica N. , Modugno, Francesmary , Nevanlinna, Heli , Palli, Domenico , Pejovic, Tanja B. , Permuth, Jennifer B. , Rebbeck, Timothy R. , Risch, Harvey A. , Senz, Janine , Setiawan, Veronica Wendy , Siddiqui, Nadeem , Swerdlow, Anthony J. , Szafron, Lukasz M. , Thomsen, Liv Cecilie Vestrheim , Tumino, Rosario , Turman, Constance , Vanderstichele, Adriaan , Edwards, Digna R. Velez , Vierkant, Robert A. , Webb, Penelope M. , Group, for the OPAL Study, Group, for the AOCS, White, Emily , Winham, Stacey J. , Yannoukakos, Drakoulis , Spurdle, Amanda B.
Cancer Epidemiology, Biomarkers & Prevention | November 3, 2020 | Volume: 30 | Issue: 1 | Pages: 217-228
Abstract 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.
Investigation of Exomic Variants Associated with Overall Survival in Ovarian Cancer
Winham, Stacey J. , Pirie, Ailith, Chen, Y. Ann , Fogarty, Zachary C. , Earp, Madalene A. , Goodman, Marc T. , Levine, Douglas A. , Menon, Usha , Ness, Roberta B., Pearce, Celeste Leigh, Rossing, Mary Anne, Wentzensen, Nicolas , Bean, Yukie T., Bisogna, Maria, Brinton, Louise A. , Carney, Michael E. , Cunningham, Julie M. , DeFazio, Anna , Dicks, Ed , Edwards, Robert P., Gayther, Simon A. , Gore, Martin, Iversen, Edwin S., Jensen, Allan , Johnatty, Sharon E., Lester, Jenny, Lin, Hui‐Yi , Lissowska, Jolanta , Lubiński, Jan , Menkiszak, Janusz , Moysich, Kirsten B. , Pike, Malcolm C. , Ramus, Susan J. , Song, Honglin , Terry, Kathryn L. , Thompson, Pamela J., Berg, David J. van den , Vierkant, Robert A. , Vitonis, Allison F., Walsh, Christine M. , Wu, Anna H. , Group, Georgia Chenevix-Trench on behalf of Australian Ovarian Cancer Study, Schildkraut, Joellen M. , Permuth‐Wey, Jennifer, Phelan, Catherine M., Sellers, Thomas A. , Goode, Ellen L. , Webb, Penelope M. , Whiteman, David C. , Chenevix‐Trench, Georgia , Bowtell, David D.L. , Ewing, Ailith , Fazio, Anna de , Larson, Melissa C. , Anton‐Culver, Hoda , Bandera, Elisa V. , Cramer, Daniel W. , Doherty, Jennifer A. , Gronwald, Jacek , Karlan, Beth Y. , Kjær, Susanne K. , Pejovic, Tanja B. , Cybulski, Cezary , Gentry‐Maharaj, Aleksandra , Modugno, Francesmary , Orlow, Irene , Tyrer, Jonathan P. , Wilkens, Lynne R. , Yang, Hannah , Ziogas, Argyrios , Berchuck, Andrew , Group, Georgia Chenevix-Trench on behalf of Australian Ovarian Cancer Study, Pharoah, Paul D.P. , Fridley, Brooke L. , Winham, Stacey J , Ramus, Susan J , Webb, Penelope M , Jensen, Allan , Vierkant, Robert A , Menon, Usha , Moysich, Kirsten , Lissowska, Jolanta , Menkiszak, Janusz , Lin, Hui-Yi , Fogarty, Zachary C , Ewing, Ailith , Chenevix-Trench, Georgia , Whiteman, David C , Bowtell, David D , Lubinski, Jan , Goodman, Marc T
Cancer Epidemiology, Biomarkers & Prevention | January 8, 2016 | Volume: 25 | Issue: 3 | Pages: 446-454
Abstract Background: While numerous susceptibility loci for epithelial ovarian cancer (EOC) have been identified, few associations have been reported with overall survival. In the absence of common prognostic genetic markers, we hypothesize that rare coding variants may be associated with overall EOC survival and assessed their contribution in two exome-based genotyping projects of the Ovarian Cancer Association Consortium (OCAC). Methods: The primary patient set (Set 1) included 14 independent EOC studies (4,293 patients) and 227,892 variants, and a secondary patient set (Set 2) included six additional EOC studies (1,744 patients) and 114,620 variants. Because power to detect rare variants individually is reduced, gene-level tests were conducted. Sets were analyzed separately at individual variants and by gene, and then combined with meta-analyses (73,203 variants and 13,163 genes overlapped). Results: No individual variant reached genome-wide statistical significance. A SNP previously implicated to be associated with EOC risk and, to a lesser extent, survival, rs8170, showed the strongest evidence of association with survival and similar effect size estimates across sets (Pmeta = 1.1E−6, HRSet1 = 1.17, HRSet2 = 1.14). Rare variants in ATG2B, an autophagy gene important for apoptosis, were significantly associated with survival after multiple testing correction (Pmeta = 1.1E−6; Pcorrected = 0.01). Conclusions: Common variant rs8170 and rare variants in ATG2B may be associated with EOC overall survival, although further study is needed. Impact: This study represents the first exome-wide association study of EOC survival to include rare variant analyses, and suggests that complementary single variant and gene-level analyses in large studies are needed to identify rare variants that warrant follow-up study. Cancer Epidemiol Biomarkers Prev; 25(3); 446–54. ©2016 AACR.