Citations 3
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.
Evaluation of vitamin D biosynthesis and pathway target genes reveals UGT2A1/2 and EGFR polymorphisms associated with epithelial ovarian cancer in African American Women
Grant, Delores J. , Alberg, Anthony J. , Barnholtz‐Sloan, Jill S. , Bondy, Melissa L. , Funkhouser, Ellen, Moorman, Patricia G. , Peres, Lauren C. , Peters, Edward , Schwartz, Ann G. , Terry, Paul , Wang, Xin‐Qun, Hoyo, Cathrine , Sandler, Dale P. , Taylor, Jack A. , Edwards, Todd L., Beeghly‐Fadiel, Alicia, Wentzensen, Nicolas , Pearce, Celeste Leigh , Wu, Anna H. , Whittemore, Alice S. , McGuire, Valerie , Sieh, Weiva , Rothstein, Joseph H. , Ness, Roberta B., Moysich, Kirsten B. , Rossing, Mary Anne, Sellers, Thomas A. , Monteiro, Álvaro N.A. , Levine, Douglas A. , Haiman, Christopher A. , Menon, Usha , Ramus, Susan J. , Gayther, Simon A. , Terry, Kathryn L. , Goode, Ellen L. , Cannioto, Rikki , Odunsi, Kunle , Etter, John Lewis , Huang, Ruea‐Yea , Bernardini, Marcus Q. , Tone, Alicia , May, Taymaa, Goodman, Marc T. , Thompson, Pamela J., Carney, Michael E. , Tworoger, Shelley S. , Lambrechts, Diether , Vergote, Ignace , Nieuwenhuysen, Els Van , Salvensen, Helga B., Massuger, Leon F.A.G. , Bruegl, Amanda , Moffitt, Melissa , Le, Nhu D. , Brooks‐Wilson, Angela , Kelemen, Linda E. , Song, Honglin , Eccles, Diana , DeFazio, Anna , Kennedy, Catherine J. , Schildkraut, Joellen M. , Lambrechts, Diether , Barnholtz-Sloan, Jill S , Moysich, Kirsten , Permuth, Jennifer B , Cramer, Daniel W , Fazio, Anna de , Lambrechts, Diether , Ramus, Susan J , Sandler, Dale P , Tworoger, Shelley S , Eccles, Diana , Menon, Usha , Monteiro, Alvaro N , Brooks-Wilson, Angela R , Kennedy, Catherine J , Lambrechts, Diether , Sieh, Weiva , Taylor, Jack A , Goodman, Marc T , Manichaikul, Ani , Bandera, Elisa V. , Coté, Michele L. , Keku, Temitope O , Berchuck, Andrew , O’Brien, Katie M. , Edwards, Digna R. Velez , Beeghly‐Fadiel, Alicia , Modugno, Francesmary , Doherty, Jennifer A. , Permuth, Jennifer B. , Setiawan, Veronica Wendy , Marchand, Loı̈c Le , Wilkens, Lynne R. , Karlan, Beth Y. , Gentry‐Maharaj, Aleksandra , Cramer, Daniel W. , Larson, Melissa C. , Kaufmann, Scott H. , Poole, Elizabeth M. , Vanderstichele, Adriaan , Anton‐Culver, Hoda , Ziogas, Argyrios , Brenton, James D. , Bjørge, Line , Kiemeney, Lambertus A. , Pejovic, Tanja B. , Cook, Linda S. , Pharoah, Paul D.P. , Campbell, Ian
Cancer Medicine | April 19, 2019 | Volume: 8 | Issue: 5 | Pages: 2503-2513
AbstractAn association between genetic variants in the vitamin D receptor (VDR) gene and epithelial ovarian cancer (EOC) was previously reported in women of African ancestry (AA). We sought to examine associations between genetic variants in VDR and additional genes from vitamin D biosynthesis and pathway targets (EGFR, UGT1A, UGT2A1/2, UGT2B, CYP3A4/5, CYP2R1, CYP27B1, CYP24A1, CYP11A1, and GC). Genotyping was performed using the custom‐designed 533,631 SNP Illumina OncoArray with imputation to the 1,000 Genomes Phase 3 v5 reference set in 755 EOC cases, including 537 high‐grade serous (HGSOC), and 1,235 controls. All subjects are of African ancestry (AA). Logistic regression was performed to estimate odds ratios (OR) and 95% confidence intervals (CI). We further evaluated statistical significance of selected SNPs using the Bayesian False Discovery Probability (BFDP). A significant association with EOC was identified in the UGT2A1/2 region for the SNP rs10017134 (per allele OR = 1.4, 95% CI = 1.2‐1.7, P = 1.2 × 10−6, BFDP = 0.02); and an association with HGSOC was identified in the EGFR region for the SNP rs114972508 (per allele OR = 2.3, 95% CI = 1.6‐3.4, P = 1.6 × 10−5, BFDP = 0.29) and in the UGT2A1/2 region again for rs1017134 (per allele OR = 1.4, 95% CI = 1.2‐1.7, P = 2.3 × 10−5, BFDP = 0.23). Genetic variants in the EGFR and UGT2A1/2 may increase susceptibility of EOC in AA women. Future studies to validate these findings are warranted. Alterations in EGFR and UGT2A1/2 could perturb enzyme efficacy, proliferation in ovaries, impact and mark susceptibility to EOC.
Analyses of germline variants associated with ovarian cancer survival identify functional candidates at the 1q22 and 19p12 outcome loci
Glubb, Dylan M. , Group, the AGO Study, Johnatty, Sharon E. , Quinn, Michael C. , O’Mara, Tracy A. , Gao, Bo , Fasching, Peter A. , Beckmann, Matthias W. , Lambrechts, Diether , Vergote, Ignace , Beeghly‐Fadiel, Alicia, Benı́tez, Javier , García, María J. , Goodman, Marc T. , Thompson, Pamela J., Dörk, Thilo , Modungo, Francesmary, Moysich, Kirsten B. , Heitz, Florian , Pfisterer, Jacobus , Hillemanns, Peter , Lester, Jenny, Goode, Ellen L. , Cunningham, Julie M. , McCauley, Bryan M. , Jensen, Allan , Schildkraut, Joellen M. , Terry, Kathryn L. , Salvesen, Helga B., Webb, Penny M., Grant, Peter J. , Moffitt, Melissa , Høgdall, Claus , Paul, James, Bernardini, Marcus Q. , Tone, Alicia , Huntsman, David, Woo, Michelle, Group, AOCS, DeFazio, Anna , Kennedy, Catherine J. , MacGregor, Stuart , Chenevix‐Trench, Georgia , Webb, Penelope M. , Bowtell, David D.L. , Lambrechts, Diether , Winham, Stacey J. , Fazio, Anna de , Group, the AGO Study, Tyrer, Jonathan P. , Edwards, Digna R. Velez , Beeghly‐Fadiel, Alicia , Dürst, Matthias , Bois, Andreas du , Karlan, Beth Y. , Larson, Melissa C. , Kjær, Susanne K. , Berchuck, Andrew , Cramer, Daniel W. , Bjørge, Line , Webb, Penny M., Pejovic, Tanja B. , Høgdall, Estrid , Glasspool, Rosalind , Group, AOCS, Pharoah, Paul D.P. , Dörk, Thilo , Lambrechts, Diether , Webb, Penelope M , Hillemanns, Peter , Jensen, Allan , Moysich, Kirsten , Kennedy, Catherine J , O'Mara, Tracy A , Heitz, Florian , Lambrechts, Diether , Quinn, Michael C J , MacGregor, Stuart , Benitez, Javier , Chenevix-Trench, Georgia , Høgdall, Claus K , Bowtell, David D , Goodman, Marc T
Oncotarget | June 15, 2017 | Volume: 8 | Issue: 39 | Pages: 64670-64684