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1. Results of a randomised Phase II trial of olaparib, chemotherapy or olaparib and cediranib in patients with platinum-resistant ovarian cancer

Author: Nicum, Shibani, McGregor, Naomi, Austin, Rachel, Collins, Linda, Dutton, Susan, McNeish, Iain, Glasspool, Rosalind, Hall, Marcia, Roux, Rene, Michael, Agnieszka, Clamp, Andrew, Jayson, Gordon, Kristeleit, Rebecca, Banerjee, Susana, and Mansouri, Anita
Published: 2024
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2. Efficacy and safety of rucaparib treatment in patients with BRCA-mutated, relapsed ovarian cancer: final results from Study 10.

Author: Kristeleit, Rebecca, Drew, Yvette, Oza, Amit, Domchek, Susan, Banerjee, Susana, Glasspool, Rosalind, Balmaña, Judith, Chen, Lee-may, Patel, Manish, Burris, Howard, Safra, Tamar, Borrow, Jennifer, Lin, Kevin, Goble, Sandra, Maloney, Lara, and Shapira-Frommer, Ronnie
Subjects: Humans, Female, BRCA2 Protein, Poly(ADP-ribose) Polymerase Inhibitors, Ovarian Neoplasms, Carcinoma, Ovarian Epithelial, Platinum, Neoplasm Recurrence, Local
Abstract: BACKGROUND: Study 10, a four-part Phase 1/2 study, evaluated oral rucaparib monotherapy in patients with advanced solid tumours. Here we report the final efficacy and safety results in heavily pretreated patients with ovarian cancer who received rucaparib in Study 10 Parts 2A and 2B. METHODS: Parts 2A and 2B (Phase 2 portions) enrolled patients with relapsed, high-grade, platinum-sensitive or platinum-resistant, BRCA-mutated ovarian cancer who had received 2-4 (Part 2A) or 3-4 (Part 2B) prior chemotherapies. Patients received oral rucaparib 600 mg twice daily (starting dose). The primary endpoint was the investigator-assessed objective response rate (ORR) by RECIST v1.1. RESULTS: Fifty-four patients were enrolled: 42 in Part 2A (all had platinum-sensitive disease) and 12 in Part 2B (4 with platinum-sensitive disease; 8 with platinum-resistant disease). ORR was 59.3% (95% CI 45.0-72.4%). The median time to onset of the most common nonhaematological treatment-emergent adverse events (TEAEs) was typically early (
Published: 2023

3. CA-125 Levels Are Predictive of Survival in Low-Grade Serous Ovarian Cancer—A Multicenter Analysis

Author: Wohlmuth, Christoph, Djedovic, Vladimir, Kjaer, Susanne K, Jensen, Allan, Glasspool, Rosalind, Roxburgh, Patricia, DeFazio, Anna, Johnatty, Sharon E, Webb, Penelope M, Modugno, Francesmary, Lambrechts, Diether, Schildkraut, Joellen M, Berchuck, Andrew, Thomsen, Liv Cecilie Vestrheim, Bjorge, Line, Høgdall, Estrid, Høgdall, Claus K, Goode, Ellen L, Winham, Stacey J, Matsuo, Keitaro, Karlan, Beth Y, Lester, Jenny, Goodman, Marc T, Thompson, Pamela J, Pejovic, Tanja, Riggan, Marjorie J, Lajkosz, Katherine, Tone, Alicia, and May, Taymaa
Subjects: Cancer, Prevention, Clinical Research, Rare Diseases, Ovarian Cancer, ovarian cancer, low-grade serous cancer, CA-125, survival, Oncology and Carcinogenesis
Abstract: ObjectiveStudies on low-grade serous ovarian cancer (LGSC) are limited by a low number of cases. The aim of this study was to define the prognostic significance of age, stage, and CA-125 levels on survival in a multi-institutional cohort of women with pathologically confirmed LGSC.MethodsWomen with LGSC were identified from the collaborative Ovarian Cancer Association Consortium (OCAC). Cases of newly diagnosed primary LGSC were included if peri-operative CA-125 levels were available. Age at diagnosis, FIGO stage, pre- and post-treatment CA-125 levels, residual disease, adjuvant chemotherapy, disease recurrence, and vital status were collected by the participating institutions. Progression-free (PFS) and overall survival (OS) were calculated. Multivariable (MVA) Cox proportional hazard models were used and hazard ratios (HR) calculated.ResultsA total of 176 women with LGSC were included in this study; 82% had stage III/IV disease. The median PFS was 2.3 years and the median OS was 6.4 years. Age at diagnosis was not significantly associated with worse PFS (p = 0.23) or OS (p = 0.3) (HR per year: 0.99; 95%CI, 0.96-1.01 and 0.98; 95%CI 0.95-1.01). FIGO stage III/IV was independently associated with PFS (HR 4.26, 95%CI 1.43-12.73) and OS (HR 1.69, 95%CI 0.56-5.05). Elevated CA-125 (≥35 U/mL) at diagnosis was not significantly associated with worse PFS (p = 0.87) or OS (p = 0.78) in MVA. Elevated CA-125 (≥35 U/mL) after completion of primary treatment was independently associated with worse PFS (HR 2.81, 95%CI 1.36-5.81) and OS (HR 6.62, 95%CI 2.45-17.92). In the MVA, residual disease was independently associated with PFS (0.022), but not OS (0.85).ConclusionAdvanced LGSC was associated with poor long-term prognosis. FIGO stage and abnormal post-treatment CA-125 level are key prognostic factors inversely associated with PFS and OS.Highlights1. Through a multi-center collaborative effort, data from 176 women with low-grade serous ovarian cancer were analyzed. 2. Although low-grade serous ovarian cancer is often considered indolent, the progression-free and overall survival are poor. 3. Elevated post-treatment CA-125 levels are independently associated with poor survival.
Published: 2022

4. Identification of a Locus Near ULK1 Associated With Progression-Free Survival in Ovarian Cancer

Author: Quinn, Michael CJ, McCue, Karen, Shi, Wei, Johnatty, Sharon E, Beesley, Jonathan, Civitarese, Andrew, O'Mara, Tracy A, Glubb, Dylan M, Tyrer, Jonathan P, Armasu, Sebastian M, Ong, Jue-Sheng, Gharahkhani, Puya, Lu, Yi, Gao, Bo, Patch, Ann-Marie, Fasching, Peter A, Beckmann, Matthias W, Lambrechts, Diether, Vergote, Ignace, Edwards, Digna R Velez, Beeghly-Fadiel, Alicia, Benitez, Javier, Garcia, Maria J, Goodman, Marc T, Dörk, Thilo, Dürst, Matthias, Modugno, Francesmary, Moysich, Kirsten, du Bois, Andreas, Pfisterer, Jacobus, Bauman, Klaus, Group, for the AGO Study, Karlan, Beth Y, Lester, Jenny, Cunningham, Julie M, Larson, Melissa C, McCauley, Bryan M, Kjaer, Susanne K, Jensen, Allan, Hogdall, Claus K, Hogdall, Estrid, Schildkraut, Joellen M, Riggan, Marjorie J, Berchuck, Andrew, Cramer, Daniel W, Terry, Kathryn L, Bjorge, Line, Webb, Penelope M, Group, for the OPAL Study, Friedlander, Michael, Pejovic, Tanja, Moffitt, Melissa, Glasspool, Rosalind, May, Taymaa, Ene, Gabrielle EV, Huntsman, David G, Woo, Michelle, Carney, Michael E, Hinsley, Samantha, Heitz, Florian, Fereday, Sian, Kennedy, Catherine J, Edwards, Stacey L, Winham, Stacey J, deFazio, Anna, Group, for Australian Ovarian Cancer Study, Pharoah, Paul DP, Goode, Ellen L, MacGregor, Stuart, and Chenevix-Trench, Georgia
Subjects: Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Prevention, Human Genome, Cancer, Genetics, Ovarian Cancer, Rare Diseases, Aetiology, 2.1 Biological and endogenous factors, Autophagy-Related Protein-1 Homolog, Biomarkers, Tumor, Carcinoma, Ovarian Epithelial, Female, Gene Knockout Techniques, Genome-Wide Association Study, Humans, Intracellular Signaling Peptides and Proteins, Ovarian Neoplasms, Polymorphism, Single Nucleotide, Progression-Free Survival, AGO Study Group, OPAL Study Group, for Australian Ovarian Cancer Study Group, Medical and Health Sciences, Epidemiology, Biomedical and clinical sciences, Health sciences
Abstract: BackgroundMany loci have been found to be associated with risk of epithelial ovarian cancer (EOC). However, although there is considerable variation in progression-free survival (PFS), no loci have been found to be associated with outcome at genome-wide levels of significance.MethodsWe carried out a genome-wide association study (GWAS) of PFS in 2,352 women with EOC who had undergone cytoreductive surgery and standard carboplatin/paclitaxel chemotherapy.ResultsWe found seven SNPs at 12q24.33 associated with PFS (P < 5 × 10-8), the top SNP being rs10794418 (HR = 1.24; 95% CI, 1.15-1.34; P = 1.47 × 10-8). High expression of a nearby gene, ULK1, is associated with shorter PFS in EOC, and with poor prognosis in other cancers. SNP rs10794418 is also associated with expression of ULK1 in ovarian tumors, with the allele associated with shorter PFS being associated with higher expression, and chromatin interactions were detected between the ULK1 promoter and associated SNPs in serous and endometrioid EOC cell lines. ULK1 knockout ovarian cancer cell lines showed significantly increased sensitivity to carboplatin in vitro.ConclusionsThe locus at 12q24.33 represents one of the first genome-wide significant loci for survival for any cancer. ULK1 is a plausible candidate for the target of this association.ImpactThis finding provides insight into genetic markers associated with EOC outcome and potential treatment options.See related commentary by Peres and Monteiro, p. 1604.
Published: 2021

5. Survival and modelled cancer antigen-125 ELIMination rate constant K score in ovarian cancer patients in first-line before poly(ADP-ribose) polymerase inhibitor era: A Gynaecologic Cancer Intergroup meta-analysis

Author: Corbaux, Pauline, You, Benoit, Glasspool, Rosalind M., Yanaihara, Nozomu, Tinker, Anna V., Lindemann, Kristina, Ray-Coquard, Isabelle L., Mirza, Mansoor R., Subtil, Fabien, Colomban, Olivier, Péron, Julien, Karamouza, Eleni, McNeish, Iain, Kelly, Caroline, Kagimura, Tatsuo, Welch, Stephen, Lewsley, Liz-Anne, Paoletti, Xavier, and Cook, Adrian
Published: 2023
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6. Cross-Cancer Genome-Wide Association Study of Endometrial Cancer and Epithelial Ovarian Cancer Identifies Genetic Risk Regions Associated with Risk of Both Cancers

Author: Glubb, Dylan M, Thompson, Deborah J, Aben, Katja KH, Alsulimani, Ahmad, Amant, Frederic, Annibali, Daniela, Attia, John, Barricarte, Aurelio, Beckmann, Matthias W, Berchuck, Andrew, Bermisheva, Marina, Bernardini, Marcus Q, Bischof, Katharina, Bjorge, Line, Bodelon, Clara, Brand, Alison H, Brenton, James D, Brinton, Louise A, Bruinsma, Fiona, Buchanan, Daniel D, Burghaus, Stefanie, Butzow, Ralf, Cai, Hui, Carney, Michael E, Chanock, Stephen J, Chen, Chu, Chen, Xiao Qing, Chen, Zhihua, Cook, Linda S, Cunningham, Julie M, De Vivo, Immaculata, deFazio, Anna, Doherty, Jennifer A, Dörk, Thilo, du Bois, Andreas, Dunning, Alison M, Dürst, Matthias, Edwards, Todd, Edwards, Robert P, Ekici, Arif B, Ewing, Ailith, Fasching, Peter A, Ferguson, Sarah, Flanagan, James M, Fostira, Florentia, Fountzilas, George, Friedenreich, Christine M, Gao, Bo, Gaudet, Mia M, Gawełko, Jan, Gentry-Maharaj, Aleksandra, Giles, Graham G, Glasspool, Rosalind, Goodman, Marc T, Gronwald, Jacek, Harris, Holly R, Harter, Philipp, Hein, Alexander, Heitz, Florian, Hildebrandt, Michelle AT, Hillemanns, Peter, Høgdall, Estrid, Høgdall, Claus K, Holliday, Elizabeth G, Huntsman, David G, Huzarski, Tomasz, Jakubowska, Anna, Jensen, Allan, Jones, Michael E, Karlan, Beth Y, Karnezis, Anthony, Kelley, Joseph L, Khusnutdinova, Elza, Killeen, Jeffrey L, Kjaer, Susanne K, Klapdor, Rüdiger, Köbel, Martin, Konopka, Bozena, Konstantopoulou, Irene, Kopperud, Reidun K, Koti, Madhuri, Kraft, Peter, Kupryjanczyk, Jolanta, Lambrechts, Diether, Larson, Melissa C, Le Marchand, Loic, Lele, Shashikant, Lester, Jenny, Li, Andrew J, Liang, Dong, Liebrich, Clemens, Lipworth, Loren, Lissowska, Jolanta, Lu, Lingeng, Lu, Karen H, Macciotta, Alessandra, Mattiello, Amalia, May, Taymaa, McAlpine, Jessica N, and McGuire, Valerie
Subjects: Epidemiology, Biomedical and Clinical Sciences, Health Sciences, Oncology and Carcinogenesis, Human Genome, Uterine Cancer, Genetics, Biotechnology, Ovarian Cancer, Prevention, Cancer, Rare Diseases, 2.1 Biological and endogenous factors, Aetiology, Carcinoma, Ovarian Epithelial, Endometrial Neoplasms, Female, Genome-Wide Association Study, Humans, Ovarian Neoplasms, Quantitative Trait Loci, Risk Factors, OPAL Study Group, AOCS Group, Medical and Health Sciences, Biomedical and clinical sciences, Health sciences
Abstract: BackgroundAccumulating 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.MethodsUsing 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.ResultsGenetic 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 (P Bonferroni < 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.ConclusionsUsing cross-cancer GWAS meta-analysis, we have identified several joint endometrial and ovarian cancer risk loci and candidate target genes for future functional analysis.ImpactOur research highlights the shared genetic relationship between endometrial cancer and ovarian cancer. Further studies in larger sample sets are required to confirm our findings.
Published: 2021

7. Development and Validation of the Gene Expression Predictor of High-grade Serous Ovarian Carcinoma Molecular SubTYPE (PrOTYPE)

Author: Talhouk, Aline, George, Joshy, Wang, Chen, Budden, Timothy, Tan, Tuan Zea, Chiu, Derek S, Kommoss, Stefan, San Leong, Huei, Chen, Stephanie, Intermaggio, Maria P, Gilks, Blake, Nazeran, Tayyebeh M, Volchek, Mila, Elatre, Wafaa, Bentley, Rex C, Senz, Janine, Lum, Amy, Chow, Veronica, Sudderuddin, Hanwei, Mackenzie, Robertson, Leong, Samuel CY, Liu, Geyi, Johnson, Dustin, Chen, Billy, Group, AOCS, Alsop, Jennifer, Banerjee, Susana N, Behrens, Sabine, Bodelon, Clara, Brand, Alison H, Brinton, Louise, Carney, Michael E, Chiew, Yoke-Eng, Cushing-Haugen, Kara L, Cybulski, Cezary, Ennis, Darren, Fereday, Sian, Fortner, Renée T, García-Donas, Jesús, Gentry-Maharaj, Aleksandra, Glasspool, Rosalind, Goranova, Teodora, Greene, Casey S, Haluska, Paul, Harris, Holly R, Hendley, Joy, Hernandez, Brenda Y, Herpel, Esther, Jimenez-Linan, Mercedes, Karpinskyj, Chloe, Kaufmann, Scott H, Keeney, Gary L, Kennedy, Catherine J, Köbel, Martin, Koziak, Jennifer M, Larson, Melissa C, Lester, Jenny, Lewsley, Liz-Anne, Lissowska, Jolanta, Lubiński, Jan, Luk, Hugh, Macintyre, Geoff, Mahner, Sven, McNeish, Iain A, Menkiszak, Janusz, Nevins, Nikilyn, Osorio, Ana, Oszurek, Oleg, Palacios, José, Hinsley, Samantha, Pearce, Celeste L, Pike, Malcolm C, Piskorz, Anna M, Ray-Coquard, Isabelle, Rhenius, Valerie, Rodriguez-Antona, Cristina, Sharma, Raghwa, Sherman, Mark E, De Silva, Dilrini, Singh, Naveena, Sinn, Peter, Slamon, Dennis, Song, Honglin, Steed, Helen, Stronach, Euan A, Thompson, Pamela J, Tołoczko, Aleksandra, Trabert, Britton, Traficante, Nadia, Tseng, Chiu-Chen, Widschwendter, Martin, Wilkens, Lynne R, Winham, Stacey J, Winterhoff, Boris, Beeghly-Fadiel, Alicia, Benitez, Javier, Berchuck, Andrew, Brenton, James D, Brown, Robert, and Chang-Claude, Jenny
Subjects: Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Rare Diseases, Orphan Drug, Genetics, Ovarian Cancer, Women's Health, Cancer Genomics, Precision Medicine, Cancer, Human Genome, 4.2 Evaluation of markers and technologies, Good Health and Well Being, Aged, Algorithms, Cystadenoma, Serous, Female, Gene Expression Regulation, Neoplastic, Humans, Lymphocytes, Tumor-Infiltrating, Middle Aged, Neoplasm Grading, Neoplasm Proteins, Neoplasm, Residual, Ovarian Neoplasms, Transcriptome, Oncology & Carcinogenesis, Clinical sciences, Oncology and carcinogenesis
Abstract: PurposeGene expression-based molecular subtypes of high-grade serous tubo-ovarian cancer (HGSOC), demonstrated across multiple studies, may provide improved stratification for molecularly targeted trials. However, evaluation of clinical utility has been hindered by nonstandardized methods, which are not applicable in a clinical setting. We sought to generate a clinical grade minimal gene set assay for classification of individual tumor specimens into HGSOC subtypes and confirm previously reported subtype-associated features.Experimental designAdopting two independent approaches, we derived and internally validated algorithms for subtype prediction using published gene expression data from 1,650 tumors. We applied resulting models to NanoString data on 3,829 HGSOCs from the Ovarian Tumor Tissue Analysis consortium. We further developed, confirmed, and validated a reduced, minimal gene set predictor, with methods suitable for a single-patient setting.ResultsGene expression data were used to derive the predictor of high-grade serous ovarian carcinoma molecular subtype (PrOTYPE) assay. We established a de facto standard as a consensus of two parallel approaches. PrOTYPE subtypes are significantly associated with age, stage, residual disease, tumor-infiltrating lymphocytes, and outcome. The locked-down clinical grade PrOTYPE test includes a model with 55 genes that predicted gene expression subtype with >95% accuracy that was maintained in all analytic and biological validations.ConclusionsWe validated the PrOTYPE assay following the Institute of Medicine guidelines for the development of omics-based tests. This fully defined and locked-down clinical grade assay will enable trial design with molecular subtype stratification and allow for objective assessment of the predictive value of HGSOC molecular subtypes in precision medicine applications.See related commentary by McMullen et al., p. 5271.
Published: 2020

8. Cross-cancer genome-wide association study of endometrial cancer and epithelial ovarian cancer identifies genetic risk regions associated with risk of both cancers

Author: Glubb, Dylan M, Thompson, Deborah J, Aben, Katja KH, Alsulimani, Ahmad, Amant, Frederic, Annibali, Daniela, Attia, John, Barricarte, Aurelio, Beckmann, Matthias W, Berchuck, Andrew, Bermisheva, Marina, Bernardini, Marcus Q, Bischof, Katharina, Bjorge, Line, Bodelon, Clara, Brand, Alison H, Brenton, James D, Brinton, Louise, Bruinsma, Fiona, Buchanan, Daniel D, Burghaus, Stefanie, Butzow, Ralf, Cai, Hui, Carney, Michael E, Chanock, Stephen J, Chen, Chu, Chen, Xiao Qing, Chen, Zhihua, Cook, Linda S, Cunningham, Julie M, De Vivo, Immaculata, deFazio, Anna, Doherty, Jennifer A, Dörk, Thilo, du Bois, Andreas, Dunning, Alison M, Dürst, Matthias, Edwards, Todd, Edwards, Robert P, Ekici, Arif B, Ewing, Ailith, Fasching, Peter A, Ferguson, Sarah, Flanagan, James M, Fostira, Florentia, Fountzilas, George, Friedenreich, Christine M, Gao, Bo, Gaudet, Mia M, Gawełko, Jan, Gentry-Maharaj, Aleksandra, Giles, Graham G, Glasspool, Rosalind, Goodman, Marc T, Gronwald, Jacek, Group, OPAL Study, Group, AOCS, Harris, Holly R, Harter, Philipp, Hein, Alexander, Heitz, Florian, Hildebrandt, Michelle AT, Hillemanns, Peter, Høgdall, Estrid, Høgdall, Claus K, Holliday, Elizabeth G, Huntsman, David G, Huzarski, Tomasz, Jakubowska, Anna, Jensen, Allan, Jones, Michael E, Karlan, Beth Y, Karnezis, Anthony, Kelley, Joseph L, Khusnutdinova, Elza, Killeen, Jeffrey L, Kjaer, Susanne K, Klapdor, Rüdiger, Köbel, Martin, Konopka, Bozena, Konstantopoulou, Irene, Kopperud, Reidun K, Koti, Madhuri, Kraft, Peter, Kupryjanczyk, Jolanta, Lambrechts, Diether, Larson, Melissa C, Le Marchand, Loic, Lele, Shashikant B, Lester, Jenny, Li, Andrew J, Liang, Dong, Liebrich, Clemens, Lipworth, Loren, Lissowska, Jolanta, Lu, Lingeng, Lu, Karen H, Macciotta, Alessandra, Mattiello, Amalia, and May, Taymaa
Subjects: Biological Sciences, Biomedical and Clinical Sciences, Genetics, Epidemiology, Health Sciences, Statistics, Mathematical Sciences, Oncology and Carcinogenesis, Aging, Rare Diseases, Human Genome, Cancer, Uterine Cancer, Ovarian Cancer, Prevention, Biotechnology, Aetiology, 2.1 Biological and endogenous factors
Abstract: Abstract: Accumulating evidence suggests a relationship between endometrial cancer and epithelial ovarian cancer. For example, endometrial cancer and epithelial ovarian cancer share epidemiological risk factors and molecular features observed across histotypes are held in common (e.g. serous, endometrioid and clear cell). Independent genome-wide association studies (GWAS) for endometrial cancer and epithelial ovarian cancer have identified 16 and 27 risk regions, respectively, four of which overlap between the two cancers. Using GWAS summary statistics, we explored the shared genetic etiology between endometrial cancer and epithelial ovarian cancer. Genetic correlation analysis using LD Score regression revealed significant genetic correlation between the two cancers (rG = 0.43, P = 2.66 × 10−5). 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 by stratified by subtype. We found seven loci associated with risk for both cancers (PBonferroni < 2.4 × 10−9). In addition, four novel regions at 7p22.2, 7q22.1, 9p12 and 11q13.3 were identified at a sub-genome wide threshold (P < 5 × 10−7). Integration with promoter-associated HiChIP chromatin loops from immortalized endometrium and epithelial ovarian cell lines, and expression quantitative trait loci (eQTL) data highlighted candidate target genes for further investigation.
Published: 2020

9. Genetic Data from Nearly 63,000 Women of European Descent Predicts DNA Methylation Biomarkers and Epithelial Ovarian Cancer Risk

Author: Yang, Yaohua, Wu, Lang, Shu, Xiang, Lu, Yingchang, Shu, Xiao-Ou, Cai, Qiuyin, Beeghly-Fadiel, Alicia, Li, Bingshan, Ye, Fei, Berchuck, Andrew, Anton-Culver, Hoda, Banerjee, Susana, Benitez, Javier, Bjørge, Line, Brenton, James D, Butzow, Ralf, Campbell, Ian G, Chang-Claude, Jenny, Chen, Kexin, Cook, Linda S, Cramer, Daniel W, deFazio, Anna, Dennis, Joe, Doherty, Jennifer A, Dörk, Thilo, Eccles, Diana M, Edwards, Digna Velez, Fasching, Peter A, Fortner, Renée T, Gayther, Simon A, Giles, Graham G, Glasspool, Rosalind M, Goode, Ellen L, Goodman, Marc T, Gronwald, Jacek, Harris, Holly R, Heitz, Florian, Hildebrandt, Michelle A, Høgdall, Estrid, Høgdall, Claus K, Huntsman, David G, Kar, Siddhartha P, Karlan, Beth Y, Kelemen, Linda E, Kiemeney, Lambertus A, Kjaer, Susanne K, Koushik, Anita, Lambrechts, Diether, Le, Nhu D, Levine, Douglas A, Massuger, Leon F, Matsuo, Keitaro, May, Taymaa, McNeish, Iain A, Menon, Usha, Modugno, Francesmary, Monteiro, Alvaro N, Moorman, Patricia G, Moysich, Kirsten B, Ness, Roberta B, Nevanlinna, Heli, Olsson, Håkan, Onland-Moret, N Charlotte, Park, Sue K, Paul, James, Pearce, Celeste L, Pejovic, Tanja, Phelan, Catherine M, Pike, Malcolm C, Ramus, Susan J, Riboli, Elio, Rodriguez-Antona, Cristina, Romieu, Isabelle, Sandler, Dale P, Schildkraut, Joellen M, Setiawan, Veronica W, Shan, Kang, Siddiqui, Nadeem, Sieh, Weiva, Stampfer, Meir J, Sutphen, Rebecca, Swerdlow, Anthony J, Szafron, Lukasz M, Teo, Soo Hwang, Tworoger, Shelley S, Tyrer, Jonathan P, Webb, Penelope M, Wentzensen, Nicolas, White, Emily, Willett, Walter C, Wolk, Alicja, Woo, Yin Ling, Wu, Anna H, Yan, Li, Yannoukakos, Drakoulis, Chenevix-Trench, Georgia, Sellers, Thomas A, Pharoah, Paul DP, Zheng, Wei, and Long, Jirong
Subjects: Biological Sciences, Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Genetics, Biotechnology, Rare Diseases, Ovarian Cancer, Cancer Genomics, Prevention, Women's Health, Cancer, Clinical Research, Human Genome, 2.1 Biological and endogenous factors, Biomarkers, Tumor, Carcinoma, Ovarian Epithelial, Cohort Studies, DNA Methylation, Female, Genetic Predisposition to Disease, Humans, Models, Genetic, Ovarian Neoplasms, Predictive Value of Tests, Risk, White People, Oncology & Carcinogenesis, Biochemistry and cell biology, Oncology and carcinogenesis
Abstract: DNA methylation is instrumental for gene regulation. Global changes in the epigenetic landscape have been recognized as a hallmark of cancer. However, the role of DNA methylation in epithelial ovarian cancer (EOC) remains unclear. In this study, high-density genetic and DNA methylation data in white blood cells from the Framingham Heart Study (N = 1,595) were used to build genetic models to predict DNA methylation levels. These prediction models were then applied to the summary statistics of a genome-wide association study (GWAS) of ovarian cancer including 22,406 EOC cases and 40,941 controls to investigate genetically predicted DNA methylation levels in association with EOC risk. Among 62,938 CpG sites investigated, genetically predicted methylation levels at 89 CpG were significantly associated with EOC risk at a Bonferroni-corrected threshold of P < 7.94 × 10-7. Of them, 87 were located at GWAS-identified EOC susceptibility regions and two resided in a genomic region not previously reported to be associated with EOC risk. Integrative analyses of genetic, methylation, and gene expression data identified consistent directions of associations across 12 CpG, five genes, and EOC risk, suggesting that methylation at these 12 CpG may influence EOC risk by regulating expression of these five genes, namely MAPT, HOXB3, ABHD8, ARHGAP27, and SKAP1. We identified novel DNA methylation markers associated with EOC risk and propose that methylation at multiple CpG may affect EOC risk via regulation of gene expression. SIGNIFICANCE: Identification of novel DNA methylation markers associated with EOC risk suggests that methylation at multiple CpG may affect EOC risk through regulation of gene expression.
Published: 2019

10. Weekly dose-dense chemotherapy in first-line epithelial ovarian, fallopian tube, or primary peritoneal cancer treatment (ICON8): overall survival results from an open-label, randomised, controlled, phase 3 trial

Author: Clamp, Andrew R, James, Elizabeth C, McNeish, Iain A, Dean, Andrew, Kim, Jae-Won, O'Donnell, Dearbhaile M, Gallardo-Rincon, Dolores, Blagden, Sarah, Brenton, James, Perren, Tim J, Sundar, Sudha, Lord, Rosemary, Dark, Graham, Hall, Marcia, Banerjee, Susana, Glasspool, Rosalind M, Hanna, C Louise, Williams, Sarah, Scatchard, Kate M, Nam, Helena, Essapen, Sharadah, Parkinson, Christine, McAvan, Lucy, Swart, Ann Marie, Popoola, Babasola, Schiavone, Francesca, Badrock, Jonathan, Fananapazir, Fuad, Cook, Adrian D, Parmar, Mahesh, Kaplan, Richard, and Ledermann, Jonathan A
Published: 2022
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11. Adult height is associated with increased risk of ovarian cancer: a Mendelian randomisation study

Author: Dixon-Suen, Suzanne C, Nagle, Christina M, Thrift, Aaron P, Pharoah, Paul DP, Ewing, Ailith, Pearce, Celeste Leigh, Zheng, Wei, Australian Ovarian Cancer Study Group, Chenevix-Trench, Georgia, Fasching, Peter A, Beckmann, Matthias W, Lambrechts, Diether, Vergote, Ignace, Lambrechts, Sandrina, Van Nieuwenhuysen, Els, Rossing, Mary Anne, Doherty, Jennifer A, Wicklund, Kristine G, Chang-Claude, Jenny, Jung, Audrey Y, Moysich, Kirsten B, Odunsi, Kunle, Goodman, Marc T, Wilkens, Lynne R, Thompson, Pamela J, Shvetsov, Yurii B, Dörk, Thilo, Park-Simon, Tjoung-Won, Hillemanns, Peter, Bogdanova, Natalia, Butzow, Ralf, Nevanlinna, Heli, Pelttari, Liisa M, Leminen, Arto, Modugno, Francesmary, Ness, Roberta B, Edwards, Robert P, Kelley, Joseph L, Heitz, Florian, du Bois, Andreas, Harter, Philipp, Schwaab, Ira, Karlan, Beth Y, Lester, Jenny, Orsulic, Sandra, Rimel, Bobbie J, Kjær, Susanne K, Høgdall, Estrid, Jensen, Allan, Goode, Ellen L, Fridley, Brooke L, Cunningham, Julie M, Winham, Stacey J, Giles, Graham G, Bruinsma, Fiona, Milne, Roger L, Southey, Melissa C, Hildebrandt, Michelle AT, Wu, Xifeng, Lu, Karen H, Liang, Dong, Levine, Douglas A, Bisogna, Maria, Schildkraut, Joellen M, Berchuck, Andrew, Cramer, Daniel W, Terry, Kathryn L, Bandera, Elisa V, Olson, Sara H, Salvesen, Helga B, Thomsen, Liv Cecilie Vestrheim, Kopperud, Reidun K, Bjorge, Line, Kiemeney, Lambertus A, Massuger, Leon FAG, Pejovic, Tanja, Bruegl, Amanda, Cook, Linda S, Le, Nhu D, Swenerton, Kenneth D, Brooks-Wilson, Angela, Kelemen, Linda E, Lubiński, Jan, Huzarski, Tomasz, Gronwald, Jacek, Menkiszak, Janusz, Wentzensen, Nicolas, Brinton, Louise, Yang, Hannah, Lissowska, Jolanta, Høgdall, Claus K, Lundvall, Lene, Song, Honglin, Tyrer, Jonathan P, Campbell, Ian, Eccles, Diana, Paul, James, Glasspool, Rosalind, Siddiqui, Nadeem, and Whittemore, Alice S
Subjects: Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Genetics, Rare Diseases, Cancer, Ovarian Cancer, Women's Health, Prevention, 2.1 Biological and endogenous factors, Adolescent, Adult, Aged, Aged, 80 and over, Body Height, Carcinoma, Ovarian Epithelial, Case-Control Studies, Female, Genetic Predisposition to Disease, Geography, Humans, Mendelian Randomization Analysis, Middle Aged, Ovarian Neoplasms, Risk Factors, Young Adult, Australian Ovarian Cancer Study Group, Ovarian Cancer Association Consortium, Public Health and Health Services, Oncology & Carcinogenesis, Oncology and carcinogenesis
Abstract: BackgroundObservational studies suggest greater height is associated with increased ovarian cancer risk, but cannot exclude bias and/or confounding as explanations for this. Mendelian randomisation (MR) can provide evidence which may be less prone to bias.MethodsWe pooled data from 39 Ovarian Cancer Association Consortium studies (16,395 cases; 23,003 controls). We applied two-stage predictor-substitution MR, using a weighted genetic risk score combining 609 single-nucleotide polymorphisms. Study-specific odds ratios (OR) and 95% confidence intervals (CI) for the association between genetically predicted height and risk were pooled using random-effects meta-analysis.ResultsGreater genetically predicted height was associated with increased ovarian cancer risk overall (pooled-OR (pOR) = 1.06; 95% CI: 1.01-1.11 per 5 cm increase in height), and separately for invasive (pOR = 1.06; 95% CI: 1.01-1.11) and borderline (pOR = 1.15; 95% CI: 1.02-1.29) tumours.ConclusionsWomen with a genetic propensity to being taller have increased risk of ovarian cancer. This suggests genes influencing height are involved in pathways promoting ovarian carcinogenesis.
Published: 2018

12. Variants in genes encoding small GTPases and association with epithelial ovarian cancer susceptibility

Author: Earp, Madalene, Tyrer, Jonathan P, Winham, Stacey J, Lin, Hui-Yi, Chornokur, Ganna, Dennis, Joe, Aben, Katja KH, Anton‐Culver, Hoda, Antonenkova, Natalia, Bandera, Elisa V, Bean, Yukie T, Beckmann, Matthias W, Bjorge, Line, Bogdanova, Natalia, Brinton, Louise A, Brooks-Wilson, Angela, Bruinsma, Fiona, Bunker, Clareann H, Butzow, Ralf, Campbell, Ian G, Carty, Karen, Chang-Claude, Jenny, Cook, Linda S, Cramer, Daniel W, Cunningham, Julie M, Cybulski, Cezary, Dansonka-Mieszkowska, Agnieszka, Despierre, Evelyn, Doherty, Jennifer A, Dörk, Thilo, du Bois, Andreas, Dürst, Matthias, Easton, Douglas F, Eccles, Diana M, Edwards, Robert P, Ekici, Arif B, Fasching, Peter A, Fridley, Brooke L, Gentry-Maharaj, Aleksandra, Giles, Graham G, Glasspool, Rosalind, Goodman, Marc T, Gronwald, Jacek, Harter, Philipp, Hein, Alexander, Heitz, Florian, Hildebrandt, Michelle AT, Hillemanns, Peter, Hogdall, Claus K, Høgdall, Estrid, Hosono, Satoyo, Iversen, Edwin S, Jakubowska, Anna, Jensen, Allan, Ji, Bu-Tian, Jung, Audrey Y, Karlan, Beth Y, Kellar, Melissa, Kiemeney, Lambertus A, Lim, Boon Kiong, Kjaer, Susanne K, Krakstad, Camilla, Kupryjanczyk, Jolanta, Lambrechts, Diether, Lambrechts, Sandrina, Le, Nhu D, Lele, Shashi, Lester, Jenny, Levine, Douglas A, Li, Zheng, Liang, Dong, Lissowska, Jolanta, Lu, Karen, Lubinski, Jan, Lundvall, Lene, Massuger, Leon FAG, Matsuo, Keitaro, McGuire, Valerie, McLaughlin, John R, McNeish, Iain, Menon, Usha, Milne, Roger L, Modugno, Francesmary, Moysich, Kirsten B, Ness, Roberta B, Nevanlinna, Heli, Odunsi, Kunle, Olson, Sara H, Orlow, Irene, Orsulic, Sandra, Paul, James, Pejovic, Tanja, Pelttari, Liisa M, Permuth, Jenny B, Pike, Malcolm C, Poole, Elizabeth M, Rosen, Barry, Rossing, Mary Anne, Rothstein, Joseph H, and Runnebaum, Ingo B
Subjects: Biochemistry and Cell Biology, Biomedical and Clinical Sciences, Biological Sciences, Genetics, Oncology and Carcinogenesis, Biotechnology, Ovarian Cancer, Cancer, Human Genome, Rare Diseases, 2.1 Biological and endogenous factors, Aetiology, A Kinase Anchor Proteins, Carcinoma, Ovarian Epithelial, Female, Genetic Association Studies, Genetic Predisposition to Disease, Genotype, Humans, Monomeric GTP-Binding Proteins, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Rho Guanine Nucleotide Exchange Factors, Risk Factors, General Science & Technology
Abstract: Epithelial ovarian cancer (EOC) is the fifth leading cause of cancer mortality in American women. Normal ovarian physiology is intricately connected to small GTP binding proteins of the Ras superfamily (Ras, Rho, Rab, Arf, and Ran) which govern processes such as signal transduction, cell proliferation, cell motility, and vesicle transport. We hypothesized that common germline variation in genes encoding small GTPases is associated with EOC risk. We investigated 322 variants in 88 small GTPase genes in germline DNA of 18,736 EOC patients and 26,138 controls of European ancestry using a custom genotype array and logistic regression fitting log-additive models. Functional annotation was used to identify biofeatures and expression quantitative trait loci that intersect with risk variants. One variant, ARHGEF10L (Rho guanine nucleotide exchange factor 10 like) rs2256787, was associated with increased endometrioid EOC risk (OR = 1.33, p = 4.46 x 10-6). Other variants of interest included another in ARHGEF10L, rs10788679, which was associated with invasive serous EOC risk (OR = 1.07, p = 0.00026) and two variants in AKAP6 (A-kinase anchoring protein 6) which were associated with risk of invasive EOC (rs1955513, OR = 0.90, p = 0.00033; rs927062, OR = 0.94, p = 0.00059). Functional annotation revealed that the two ARHGEF10L variants were located in super-enhancer regions and that AKAP6 rs927062 was associated with expression of GTPase gene ARHGAP5 (Rho GTPase activating protein 5). Inherited variants in ARHGEF10L and AKAP6, with potential transcriptional regulatory function and association with EOC risk, warrant investigation in independent EOC study populations.
Published: 2018

13. Incorporating patient centered benefits as endpoints in randomized trials of maintenance therapies in advanced ovarian cancer: A position paper from the GCIG symptom benefit committee

Author: Kurtz, Jean-Emmanuel, Gebski, Val, Sukhin, Vladyslav, Carey, Mark, Kong, Iwa, Glasspool, Rosalind M., Berek, Jonathan S., de Paiva Batista, Mariana, Hall, Marcia, Kim, Jae-Weon, Yeoshoua, Effi, Fujiwara, Noriko, Nam, Byung-Ho, Polleis, Sandra, Lee, Jung-Yun, Strojna, Aleksandra, Farrelly, Laura, Schwameis, Richard, Fossati, Roldano, Darlington, Anne-Sophie, Lai, Chyong-Huey, Wright, Alexi A., Rosenblat, Orgad, Harter, Phillip, Roxburgh, Patricia, Chowdhury, Rahul Roy, Chang, Ting-Chang, Paoletti, Xavier, and Friedlander, Michael
Published: 2021
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14. Objective responses to first-line neoadjuvant carboplatin–paclitaxel regimens for ovarian, fallopian tube, or primary peritoneal carcinoma (ICON8): post-hoc exploratory analysis of a randomised, phase 3 trial

Author: Morgan, Robert D, McNeish, Iain A, Cook, Adrian D, James, Elizabeth C, Lord, Rosemary, Dark, Graham, Glasspool, Rosalind M, Krell, Jonathan, Parkinson, Christine, Poole, Christopher J, Hall, Marcia, Gallardo-Rincón, Dolores, Lockley, Michelle, Essapen, Sharadah, Summers, Jeff, Anand, Anjana, Zachariah, Abel, Williams, Sarah, Jones, Rachel, Scatchard, Kate, Walther, Axel, Kim, Jae-Weon, Sundar, Sudha, Jayson, Gordon C, Ledermann, Jonathan A, and Clamp, Andrew R
Published: 2021
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15. Analyses of germline variants associated with ovarian cancer survival identify functional candidates at the 1q22 and 19p12 outcome loci

Author: Glubb, Dylan M, Johnatty, Sharon E, Quinn, Michael CJ, O’Mara, Tracy A, Tyrer, Jonathan P, Gao, Bo, Fasching, Peter A, Beckmann, Matthias W, Lambrechts, Diether, Vergote, Ignace, Velez Edwards, Digna R, Beeghly-Fadiel, Alicia, Benitez, Javier, Garcia, Maria J, Goodman, Marc T, Thompson, Pamela J, Dörk, Thilo, Dürst, Matthias, Modungo, Francesmary, Moysich, Kirsten, Heitz, Florian, du Bois, Andreas, Pfisterer, Jacobus, Hillemanns, Peter, Karlan, Beth Y, Lester, Jenny, Goode, Ellen L, Cunningham, Julie M, Winham, Stacey J, Larson, Melissa C, McCauley, Bryan M, Kjær, Susanne Krüger, Jensen, Allan, Schildkraut, Joellen M, Berchuck, Andrew, Cramer, Daniel W, Terry, Kathryn L, Salvesen, Helga B, Bjorge, Line, Webb, Penny M, Grant, Peter, Pejovic, Tanja, Moffitt, Melissa, Hogdall, Claus K, Hogdall, Estrid, Paul, James, Glasspool, Rosalind, Bernardini, Marcus, Tone, Alicia, Huntsman, David, Woo, Michelle, Group, AOCS, deFazio, Anna, Kennedy, Catherine J, Pharoah, Paul DP, MacGregor, Stuart, and Chenevix-Trench, Georgia
Subjects: Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Orphan Drug, Cancer, Rare Diseases, Prevention, Genetics, Ovarian Cancer, Aetiology, 2.1 Biological and endogenous factors, ovarian cancer outcome, genetic association, gene regulation, meta-analysis, Oncology and carcinogenesis
Abstract: We previously identified associations with ovarian cancer outcome at five genetic loci. To identify putatively causal genetic variants and target genes, we prioritized two ovarian outcome loci (1q22 and 19p12) for further study. Bioinformatic and functional genetic analyses indicated that MEF2D and ZNF100 are targets of candidate outcome variants at 1q22 and 19p12, respectively. At 19p12, the chromatin interaction of a putative regulatory element with the ZNF100 promoter region correlated with candidate outcome variants. At 1q22, putative regulatory elements enhanced MEF2D promoter activity and haplotypes containing candidate outcome variants modulated these effects. In a public dataset, MEF2D and ZNF100 expression were both associated with ovarian cancer progression-free or overall survival time. In an extended set of 6,162 epithelial ovarian cancer patients, we found that functional candidates at the 1q22 and 19p12 loci, as well as other regional variants, were nominally associated with patient outcome; however, no associations reached our threshold for statistical significance (p
Published: 2017

16. No Evidence That Genetic Variation in the Myeloid-Derived Suppressor Cell Pathway Influences Ovarian Cancer Survival

Author: Sucheston-Campbell, Lara E, Cannioto, Rikki, Clay, Alyssa I, Etter, John Lewis, Eng, Kevin H, Liu, Song, Battaglia, Sebastiano, Hu, Qiang, Szender, J Brian, Minlikeeva, Albina, Joseph, Janine M, Mayor, Paul, Abrams, Scott I, Segal, Brahm H, Wallace, Paul K, Soh, Kah Teong, Zsiros, Emese, Anton-Culver, Hoda, Bandera, Elisa V, Beckmann, Matthias W, Berchuck, Andrew, Bjorge, Line, Bruegl, Amanda, Campbell, Ian G, Campbell, Shawn Patrice, Chenevix-Trench, Georgia, Study, on behalf of the Australian Ovarian Cancer, Cramer, Daniel W, Dansonka-Mieszkowska, Agnieszka, Dao, Fanny, Diergaarde, Brenda, Doerk, Thilo, Doherty, Jennifer A, du Bois, Andreas, Eccles, Diana, Engelholm, Svend Aage, Fasching, Peter A, Gayther, Simon A, Gentry-Maharaj, Aleksandra, Glasspool, Rosalind M, Goodman, Marc T, Gronwald, Jacek, Harter, Philipp, Hein, Alexander, Heitz, Florian, Hillemmanns, Peter, Høgdall, Claus, Høgdall, Estrid VS, Huzarski, Tomasz, Jensen, Allan, Johnatty, Sharon E, Jung, Audrey, Karlan, Beth Y, Klapdor, Reudiger, Kluz, Tomasz, Konopka, Bożena, Kjær, Susanne Krüger, Kupryjanczyk, Jolanta, Lambrechts, Diether, Lester, Jenny, Lubiński, Jan, Levine, Douglas A, Lundvall, Lene, McGuire, Valerie, McNeish, Iain A, Menon, Usha, Modugno, Francesmary, Ness, Roberta B, Orsulic, Sandra, Paul, James, Pearce, Celeste Leigh, Pejovic, Tanja, Pharoah, Paul, Ramus, Susan J, Rothstein, Joseph, Rossing, Mary Anne, Rübner, Matthias, Schildkraut, Joellen M, Schmalfeldt, Barbara, Schwaab, Ira, Siddiqui, Nadeem, Sieh, Weiva, Sobiczewski, Piotr, Song, Honglin, Terry, Kathryn L, Van Nieuwenhuysen, Els, Vanderstichele, Adriaan, Vergote, Ignace, Walsh, Christine S, Webb, Penelope M, Wentzensen, Nicolas, Whittemore, Alice S, Wu, Anna H, Ziogas, Argyrios, Odunsi, Kunle, Chang-Claude, Jenny, Goode, Ellen L, and Moysich, Kirsten B
Subjects: Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Immunology, Clinical Research, Cancer, Ovarian Cancer, Rare Diseases, Prevention, Genetics, Genetic Testing, 2.1 Biological and endogenous factors, Aetiology, Carcinoma, Ovarian Epithelial, Female, Genetic Association Studies, Genetic Variation, Humans, Myeloid-Derived Suppressor Cells, Neoplasms, Glandular and Epithelial, Ovarian Neoplasms, Australian Ovarian Cancer Study, Medical and Health Sciences, Epidemiology, Biomedical and clinical sciences, Health sciences
Abstract: Background: The precise mechanism by which the immune system is adversely affected in cancer patients remains poorly understood, but the accumulation of immunosuppressive/protumorigenic myeloid-derived suppressor cells (MDSCs) is thought to be a prominent mechanism contributing to immunologic tolerance of malignant cells in epithelial ovarian cancer (EOC). To this end, we hypothesized genetic variation in MDSC pathway genes would be associated with survival after EOC diagnoses.Methods: We measured the hazard of death due to EOC within 10 years of diagnosis, overall and by invasive subtype, attributable to SNPs in 24 genes relevant in the MDSC pathway in 10,751 women diagnosed with invasive EOC. Versatile Gene-based Association Study and the admixture likelihood method were used to test gene and pathway associations with survival.Results: We did not identify individual SNPs that were significantly associated with survival after correction for multiple testing (P < 3.5 × 10-5), nor did we identify significant associations between the MDSC pathway overall, or the 24 individual genes and EOC survival.Conclusions: In this well-powered analysis, we observed no evidence that inherited variations in MDSC-associated SNPs, individual genes, or the collective genetic pathway contributed to EOC survival outcomes.Impact: Common inherited variation in genes relevant to MDSCs was not associated with survival in women diagnosed with invasive EOC. Cancer Epidemiol Biomarkers Prev; 26(3); 420-4. ©2016 AACR.
Published: 2017

17. Bevacizumab and platinum-based combinations for recurrent ovarian cancer: a randomised, open-label, phase 3 trial

Author: Ackermann, Sven, Anthuber, Christoph, Aydogdu, Mustafa, Baldauf, Angelika, Bauer, Wolfgang, Behringer, Dirk, Belau, Antje, Bender, Alexandra, Brucker, Cosima, Burges, Alexander, Canzler, Ulrich, Daabach, Trygve, Denschlag, Dominik, Deryal, Mustafa, Dörfel, Steffen, Ebert, Juliane, El-Balat, Ahmed, Fehm, Tanja, Feidicker, Susanne Maria, Feisel-Schwickardi, Gabriele, Felberbaum, Ricardo, Frank, Matthias, Gebauer, Gerhard, Gerber, Bernd, Gerhardt, Axel, Grafe, Andrea, Griesshammer, Martin, Grischke, Eva-Maria, Gröll, Isolde, Gropp-Meier, Martina, Hager, Dietrich, Hanf, Volker, Hannig, Carla Verena, Hantschmann, Peer, Harter, Philipp, Hauzenberger, Tanja, Herwig, Uwe, Heubner, Martin, Hielscher, Carsten, Hilpert, Felix, Hitschold, Thomas, Hofmann, Manfred, Jackisch, Christian, Janni, Wolfgang, Kiesel, Ludwig, Ko, Yon-Dschun, Koch, Hans-Joachim, Krabisch, Petra, Krieger, Peter, Kubin, Thomas, Kühn, Thorsten, Lampe, Björn, Ledwon, Peter, Lemster, Sabine, Lex, Benno, Liebrich, Clemens, Lorenz, Ralf, Lück, Hans-Joachim, Mahner, Sven, Mallmann, Peter, Marmé, Frederik, Meier, Werner, Meinerz, Wolfgang, Menke, Götz, Möbus, Volker, Müller, Thomas, Müller, Volker, Neunhöffer, Tanja, Ober, Angelika, Oskay-Özcelik, Gülten, Ostertag, Horst, Park-Simon, Tjoung-Won, Pölcher, Martin, Rautenberg, Beate, Rein, Daniel, Reiter, Wilhelm, Rempen, Andreas, Runnebaum, Ingo, Schmalfeldt, Barbara, Schmidt, Marcus, Schnohr, Sabine, Scholz, Heinz, Schröder, Willibald, Sehouli, Jalid, Simon, Eike, Sperfeld, Antje, Steckkönig, Annette, Strauß, Hans-Georg, Stuth, Ronaldo, Terhaag, Jürgen, Thiel, Falk, Thill, Marc, Tomé, Oliver, Uleer, Christoph, Vogel, Susanne, Voß, Hermann, Weigel, Michael, Winkler, Ulrich, Wischnik, Arthur, Zeiser, Tobias, Zorr, Andreas, Glasspool, Ros, Hudson, Emma, Jones, Rachel, Lafleur, Judith, Marth, Christian, Petru, Edgar, Reinthaller, Alexander, Antill, Yoland, Azer, Mary, Baron-Hay, Sally, Beale, Philip, Begbie, Stephen, Black, Allison, Briscoe, Karen, Dean, Andrew, Goh, Jeffrey, Harvey, Sandra, Lee, Chee, Matos, Marco, Meniawy, Tarek, Olesen, Inger, Shannon, Catherine, Vasey, Paul, Abadie-Lacourtoisie, Sophie, Arsene, Olivier, Barthier, Sophie, Becuwe-Roemer, Célia, Berton-Rigaud, Dominique, Cappiello-Bataller, Maria, Catala, Stéphanie, Costan, Cristina, Del Piano, Francesco, Deplanque, Gaël, Despax, Raymond, Dohollou, Nadine, Garnier-Tixidré, Claire, Grenier, Julien, Guardiola, Emmanuel, Hardy-Bessard, Anne-Claire, Joly, Florence, Kurtz, Jean-Emmanuel, Lefeuvre-Plesse, Claudia, Leheurteur, Marianne, Lesoin, Anne, Levache, Charles-Briac, L'Haridon, Tifenn, Longo, Raffaele, Lortholary, Alain, Meunier, Jérôme, Mouret-Reynier, Marie-Ange, Petit, Thierry, Raban, Nadia, Romano, Olivier, Vannetzel, Jean-Michel, Zannetti, Alain, Pfisterer, Jacobus, Shannon, Catherine M, Baumann, Klaus, Rau, Joern, Dean, Andrew P, Hein, Alexander, Zeimet, Alain G, Hanker, Lars C, Glasspool, Rosalind, de Gregorio, Nikolaus, Meniawy, Tarek M, Goh, Jeffrey C, Baron Hay, Sally, Kommoss, Stefan, and du Bois, Andreas
Published: 2020
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18. Assessment of variation in immunosuppressive pathway genes reveals TGFBR2 to be associated with risk of clear cell ovarian cancer

Author: Hampras, Shalaka S, Sucheston-Campbell, Lara E, Cannioto, Rikki, Chang-Claude, Jenny, Modugno, Francesmary, Dörk, Thilo, Hillemanns, Peter, Preus, Leah, Knutson, Keith L, Wallace, Paul K, Hong, Chi-Chen, Friel, Grace, Davis, Warren, Nesline, Mary, Pearce, Celeste L, Kelemen, Linda E, Goodman, Marc T, Bandera, Elisa V, Terry, Kathryn L, Schoof, Nils, Eng, Kevin H, Clay, Alyssa, Singh, Prashant K, Joseph, Janine M, Aben, Katja KH, Anton-Culver, Hoda, Antonenkova, Natalia, Baker, Helen, Bean, Yukie, Beckmann, Matthias W, Bisogna, Maria, Bjorge, Line, Bogdanova, Natalia, Brinton, Louise A, Brooks-Wilson, Angela, Bruinsma, Fiona, Butzow, Ralf, Campbell, Ian G, Carty, Karen, Cook, Linda S, Cramer, Daniel W, Cybulski, Cezary, Dansonka-Mieszkowska, Agnieszka, Dennis, Joe, Despierre, Evelyn, Dicks, Ed, Doherty, Jennifer A, du Bois, Andreas, Dürst, Matthias, Easton, Doug, Eccles, Diana, Edwards, Robert P, Ekici, Arif B, Fasching, Peter A, Fridley, Brooke L, Gao, Yu-Tang, Gentry-Maharaj, Aleksandra, Giles, Graham G, Glasspool, Rosalind, Gronwald, Jacek, Harrington, Patricia, Harter, Philipp, Hasmad, Hanis Nazihah, Hein, Alexander, Heitz, Florian, Hildebrandt, Michelle AT, Hogdall, Claus, Hogdall, Estrid, Hosono, Satoyo, Iversen, Edwin S, Jakubowska, Anna, Jensen, Allan, Ji, Bu-Tian, Karlan, Beth Y, Kellar, Melissa, Kelley, Joseph L, Kiemeney, Lambertus A, Klapdor, Rüdiger, Kolomeyevskaya, Nonna, Krakstad, Camilla, Kjaer, Susanne K, Kruszka, Bridget, Kupryjanczyk, Jolanta, Lambrechts, Diether, Lambrechts, Sandrina, Le, Nhu D, Lee, Alice W, Lele, Shashikant, Leminen, Arto, Lester, Jenny, Levine, Douglas A, Liang, Dong, Lissowska, Jolanta, Liu, Song, Lu, Karen, Lubinski, Jan, Lundvall, Lene, Massuger, Leon FAG, Matsuo, Keitaro, and McGuire, Valeria
Subjects: Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Immunology, Ovarian Cancer, Rare Diseases, Cancer, Genetics, 2.1 Biological and endogenous factors, Aetiology, Adenocarcinoma, Clear Cell, Adult, Aged, Carcinoma, Ovarian Epithelial, Female, Gene Expression Regulation, Neoplastic, Gene Frequency, Genetic Predisposition to Disease, Genotype, Humans, Middle Aged, Neoplasms, Glandular and Epithelial, Ovarian Neoplasms, Polymorphism, Single Nucleotide, Protein Serine-Threonine Kinases, Receptor, Transforming Growth Factor-beta Type II, Receptors, Transforming Growth Factor beta, Risk Factors, T-Lymphocytes, Regulatory, ovarian cancer, immunosuppression, biomarkers, genetic variation, TGFBR2, TGFBR2, Oncology and carcinogenesis
Abstract: BackgroundRegulatory T (Treg) cells, a subset of CD4+ T lymphocytes, are mediators of immunosuppression in cancer, and, thus, variants in genes encoding Treg cell immune molecules could be associated with ovarian cancer.MethodsIn a population of 15,596 epithelial ovarian cancer (EOC) cases and 23,236 controls, we measured genetic associations of 1,351 SNPs in Treg cell pathway genes with odds of ovarian cancer and tested pathway and gene-level associations, overall and by histotype, for the 25 genes, using the admixture likelihood (AML) method. The most significant single SNP associations were tested for correlation with expression levels in 44 ovarian cancer patients.ResultsThe most significant global associations for all genes in the pathway were seen in endometrioid ( p = 0.082) and clear cell ( p = 0.083), with the most significant gene level association seen with TGFBR2 ( p = 0.001) and clear cell EOC. Gene associations with histotypes at p < 0.05 included: IL12 ( p = 0.005 and p = 0.008, serous and high-grade serous, respectively), IL8RA ( p = 0.035, endometrioid and mucinous), LGALS1 ( p = 0.03, mucinous), STAT5B ( p = 0.022, clear cell), TGFBR1 ( p = 0.021 endometrioid) and TGFBR2 ( p = 0.017 and p = 0.025, endometrioid and mucinous, respectively).ConclusionsCommon inherited gene variation in Treg cell pathways shows some evidence of germline genetic contribution to odds of EOC that varies by histologic subtype and may be associated with mRNA expression of immune-complex receptor in EOC patients.
Published: 2016

19. Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus.

Author: Lawrenson, Kate, Kar, Siddhartha, McCue, Karen, Kuchenbaeker, Karoline, Michailidou, Kyriaki, Tyrer, Jonathan, Beesley, Jonathan, Ramus, Susan J, Li, Qiyuan, Delgado, Melissa K, Lee, Janet M, Aittomäki, Kristiina, Andrulis, Irene L, Anton-Culver, Hoda, Arndt, Volker, Arun, Banu K, Arver, Brita, Bandera, Elisa V, Barile, Monica, Barkardottir, Rosa B, Barrowdale, Daniel, Beckmann, Matthias W, Benitez, Javier, Berchuck, Andrew, Bisogna, Maria, Bjorge, Line, Blomqvist, Carl, Blot, William, Bogdanova, Natalia, Bojesen, Anders, Bojesen, Stig E, Bolla, Manjeet K, Bonanni, Bernardo, Børresen-Dale, Anne-Lise, Brauch, Hiltrud, Brennan, Paul, Brenner, Hermann, Bruinsma, Fiona, Brunet, Joan, Buhari, Shaik Ahmad, Burwinkel, Barbara, Butzow, Ralf, Buys, Saundra S, Cai, Qiuyin, Caldes, Trinidad, Campbell, Ian, Canniotto, Rikki, Chang-Claude, Jenny, Chiquette, Jocelyne, Choi, Ji-Yeob, Claes, Kathleen BM, GEMO Study Collaborators, Cook, Linda S, Cox, Angela, Cramer, Daniel W, Cross, Simon S, Cybulski, Cezary, Czene, Kamila, Daly, Mary B, Damiola, Francesca, Dansonka-Mieszkowska, Agnieszka, Darabi, Hatef, Dennis, Joe, Devilee, Peter, Diez, Orland, Doherty, Jennifer A, Domchek, Susan M, Dorfling, Cecilia M, Dörk, Thilo, Dumont, Martine, Ehrencrona, Hans, Ejlertsen, Bent, Ellis, Steve, EMBRACE, Engel, Christoph, Lee, Eunjung, Evans, D Gareth, Fasching, Peter A, Feliubadalo, Lidia, Figueroa, Jonine, Flesch-Janys, Dieter, Fletcher, Olivia, Flyger, Henrik, Foretova, Lenka, Fostira, Florentia, Foulkes, William D, Fridley, Brooke L, Friedman, Eitan, Frost, Debra, Gambino, Gaetana, Ganz, Patricia A, Garber, Judy, García-Closas, Montserrat, Gentry-Maharaj, Aleksandra, Ghoussaini, Maya, Giles, Graham G, Glasspool, Rosalind, Godwin, Andrew K, Goldberg, Mark S, and Goldgar, David E
Subjects: GEMO Study Collaborators, EMBRACE, Hereditary Breast and Ovarian Cancer Research Group Netherlands, KConFab Investigators, Australian Ovarian Cancer Study Group, Chromosomes, Human, Pair 19, Humans, Breast Neoplasms, Ovarian Neoplasms, Genetic Predisposition to Disease, RNA, Messenger, Genotype, Polymorphism, Single Nucleotide, Alleles, African Continental Ancestry Group, Asian Continental Ancestry Group, Female, Genome-Wide Association Study, Chromosomes, Human, Pair 19, RNA, Messenger, Polymorphism, Single Nucleotide, Prevention, Breast Cancer, Ovarian Cancer, Cancer, Rare Diseases, Genetics, 2.1 Biological and endogenous factors
Abstract: A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10(-20)), ER-negative BC (P=1.1 × 10(-13)), BRCA1-associated BC (P=7.7 × 10(-16)) and triple negative BC (P-diff=2 × 10(-5)). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P=2 × 10(-3)) and ABHD8 (P
Published: 2016

20. Analysis of Anxiety, Depression and Fear of Progression at 12 Months Post-Cytoreductive Surgery in the SOCQER-2 (Surgery in Ovarian Cancer—Quality of Life Evaluation Research) Prospective, International, Multicentre Study

Author: Lakhiani, Aarti, primary, Cummins, Carole, additional, Kumar, Satyam, additional, Long, Joanna, additional, Arora, Vivek, additional, Balega, Janos, additional, Broadhead, Tim, additional, Duncan, Timothy, additional, Edmondson, Richard, additional, Fotopoulou, Christina, additional, Glasspool, Rosalind, additional, Kolomainen, Desiree, additional, Manchanda, Ranjit, additional, McNally, Orla, additional, Morrison, Jo, additional, Mukhopadhyay, Asima, additional, Naik, Raj, additional, Wood, Nick, additional, and Sundar, Sudha, additional
Published: 2023
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21. Genome-wide Analysis Identifies Novel Loci Associated with Ovarian Cancer Outcomes: Findings from the Ovarian Cancer Association Consortium

Author: Johnatty, Sharon E, Group, on behalf of the Australian Ovarian Cancer Study, Tyrer, Jonathan P, Kar, Siddhartha, Beesley, Jonathan, Lu, Yi, Gao, Bo, Fasching, Peter A, Hein, Alexander, Ekici, Arif B, Beckmann, Matthias W, Lambrechts, Diether, Van Nieuwenhuysen, Els, Vergote, Ignace, Lambrechts, Sandrina, Rossing, Mary Anne, Doherty, Jennifer A, Chang-Claude, Jenny, Modugno, Francesmary, Ness, Roberta B, Moysich, Kirsten B, Levine, Douglas A, Kiemeney, Lambertus A, Massuger, Leon FAG, Gronwald, Jacek, Lubiński, Jan, Jakubowska, Anna, Cybulski, Cezary, Brinton, Louise, Lissowska, Jolanta, Wentzensen, Nicolas, Song, Honglin, Rhenius, Valerie, Campbell, Ian, Eccles, Diana, Sieh, Weiva, Whittemore, Alice S, McGuire, Valerie, Rothstein, Joseph H, Sutphen, Rebecca, Anton-Culver, Hoda, Ziogas, Argyrios, Gayther, Simon A, Gentry-Maharaj, Aleksandra, Menon, Usha, Ramus, Susan J, Pearce, Celeste L, Pike, Malcolm C, Stram, Daniel O, Wu, Anna H, Kupryjanczyk, Jolanta, Dansonka-Mieszkowska, Agnieszka, Rzepecka, Iwona K, Spiewankiewicz, Beata, Goodman, Marc T, Wilkens, Lynne R, Carney, Michael E, Thompson, Pamela J, Heitz, Florian, du Bois, Andreas, Schwaab, Ira, Harter, Philipp, Pisterer, Jacobus, Hillemanns, Peter, Group, on behalf of the AGO Study, Karlan, Beth Y, Walsh, Christine, Lester, Jenny, Orsulic, Sandra, Winham, Stacey J, Earp, Madalene, Larson, Melissa C, Fogarty, Zachary C, Høgdall, Estrid, Jensen, Allan, Kjaer, Susanne Kruger, Fridley, Brooke L, Cunningham, Julie M, Vierkant, Robert A, Schildkraut, Joellen M, Iversen, Edwin S, Terry, Kathryn L, Cramer, Daniel W, Bandera, Elisa V, Orlow, Irene, Pejovic, Tanja, Bean, Yukie, Høgdall, Claus, Lundvall, Lene, McNeish, Ian, Paul, James, Carty, Karen, Siddiqui, Nadeem, Glasspool, Rosalind, Sellers, Thomas, Kennedy, Catherine, Chiew, Yoke-Eng, Berchuck, Andrew, MacGregor, Stuart, and Pharoah, Paul DP
Subjects: Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Orphan Drug, Genetics, Human Genome, Precision Medicine, Rare Diseases, Women's Health, Cancer Genomics, Ovarian Cancer, Cancer, 2.1 Biological and endogenous factors, Aetiology, Alleles, Carcinoma, Ovarian Epithelial, Computational Biology, Female, Genome-Wide Association Study, Genotype, Humans, Kaplan-Meier Estimate, Meta-Analysis as Topic, Neoplasms, Glandular and Epithelial, Ovarian Neoplasms, Patient Outcome Assessment, Polymorphism, Single Nucleotide, Prognosis, Quantitative Trait Loci, AGO Study Group, Australian Ovarian Cancer Study Group, Oncology & Carcinogenesis, Clinical sciences, Oncology and carcinogenesis
Abstract: PurposeChemotherapy resistance remains a major challenge in the treatment of ovarian cancer. We hypothesize that germline polymorphisms might be associated with clinical outcome.Experimental designWe analyzed approximately 2.8 million genotyped and imputed SNPs from the iCOGS experiment for progression-free survival (PFS) and overall survival (OS) in 2,901 European epithelial ovarian cancer (EOC) patients who underwent first-line treatment of cytoreductive surgery and chemotherapy regardless of regimen, and in a subset of 1,098 patients treated with ≥ 4 cycles of paclitaxel and carboplatin at standard doses. We evaluated the top SNPs in 4,434 EOC patients, including patients from The Cancer Genome Atlas. In addition, we conducted pathway analysis of all intragenic SNPs and tested their association with PFS and OS using gene set enrichment analysis.ResultsFive SNPs were significantly associated (P ≤ 1.0 × 10(-5)) with poorer outcomes in at least one of the four analyses, three of which, rs4910232 (11p15.3), rs2549714 (16q23), and rs6674079 (1q22), were located in long noncoding RNAs (lncRNAs) RP11-179A10.1, RP11-314O13.1, and RP11-284F21.8, respectively (P ≤ 7.1 × 10(-6)). ENCODE ChIP-seq data at 1q22 for normal ovary show evidence of histone modification around RP11-284F21.8, and rs6674079 is perfectly correlated with another SNP within the super-enhancer MEF2D, expression levels of which were reportedly associated with prognosis in another solid tumor. YAP1- and WWTR1 (TAZ)-stimulated gene expression and high-density lipoprotein (HDL)-mediated lipid transport pathways were associated with PFS and OS, respectively, in the cohort who had standard chemotherapy (pGSEA ≤ 6 × 10(-3)).ConclusionsWe have identified SNPs in three lncRNAs that might be important targets for novel EOC therapies.
Published: 2015

22. Epithelial-Mesenchymal Transition (EMT) Gene Variants and Epithelial Ovarian Cancer (EOC) Risk.

Author: Amankwah, Ernest K, Lin, Hui-Yi, Tyrer, Jonathan P, Lawrenson, Kate, Dennis, Joe, Chornokur, Ganna, Aben, Katja KH, Anton-Culver, Hoda, Antonenkova, Natalia, Bruinsma, Fiona, Bandera, Elisa V, Bean, Yukie T, Beckmann, Matthias W, Bisogna, Maria, Bjorge, Line, Bogdanova, Natalia, Brinton, Louise A, Brooks-Wilson, Angela, Bunker, Clareann H, Butzow, Ralf, Campbell, Ian G, Carty, Karen, Chen, Zhihua, Chen, Y Ann, Chang-Claude, Jenny, Cook, Linda S, Cramer, Daniel W, Cunningham, Julie M, Cybulski, Cezary, Dansonka-Mieszkowska, Agnieszka, du Bois, Andreas, Despierre, Evelyn, Dicks, Ed, Doherty, Jennifer A, Dörk, Thilo, Dürst, Matthias, Easton, Douglas F, Eccles, Diana M, Edwards, Robert P, Ekici, Arif B, Fasching, Peter A, Fridley, Brooke L, Gao, Yu-Tang, Gentry-Maharaj, Aleksandra, Giles, Graham G, Glasspool, Rosalind, Goodman, Marc T, Gronwald, Jacek, Harrington, Patricia, Harter, Philipp, Hasmad, Hanis N, Hein, Alexander, Heitz, Florian, Hildebrandt, Michelle AT, Hillemanns, Peter, Hogdall, Claus K, Hogdall, Estrid, Hosono, Satoyo, Iversen, Edwin S, Jakubowska, Anna, Jensen, Allan, Ji, Bu-Tian, Karlan, Beth Y, Jim, Heather, Kellar, Melissa, Kiemeney, Lambertus A, Krakstad, Camilla, Kjaer, Susanne K, Kupryjanczyk, Jolanta, Lambrechts, Diether, Lambrechts, Sandrina, Le, Nhu D, Lee, Alice W, Lele, Shashi, Leminen, Arto, Lester, Jenny, Levine, Douglas A, Liang, Dong, Lim, Boon Kiong, Lissowska, Jolanta, Lu, Karen, Lubinski, Jan, Lundvall, Lene, Massuger, Leon FAG, Matsuo, Keitaro, McGuire, Valerie, McLaughlin, John R, McNeish, Ian, Menon, Usha, Milne, Roger L, Modugno, Francesmary, Moysich, Kirsten B, Ness, Roberta B, Nevanlinna, Heli, Eilber, Ursula, Odunsi, Kunle, Olson, Sara H, Orlow, Irene, Orsulic, Sandra, and Weber, Rachel Palmieri
Subjects: Georgia Chenevix-Trench on behalf of the AOCS management group, Humans, Neoplasms, Glandular and Epithelial, Ovarian Neoplasms, Genetic Predisposition to Disease, Odds Ratio, Risk, Genotype, Polymorphism, Single Nucleotide, Adult, Aged, Middle Aged, European Continental Ancestry Group, Female, Genome-Wide Association Study, Epithelial-Mesenchymal Transition, Carcinoma, Ovarian Epithelial, epithelial-mesenchymal transition, ovarian cancer, single-nucleotide polymorphisms, Neoplasms, Glandular and Epithelial, Polymorphism, Single Nucleotide, Carcinoma, Ovarian Epithelial, Epidemiology, Public Health and Health Services, Genetics
Abstract: Epithelial-mesenchymal transition (EMT) is a process whereby epithelial cells assume mesenchymal characteristics to facilitate cancer metastasis. However, EMT also contributes to the initiation and development of primary tumors. Prior studies that explored the hypothesis that EMT gene variants contribute to epithelial ovarian carcinoma (EOC) risk have been based on small sample sizes and none have sought replication in an independent population. We screened 15,816 single-nucleotide polymorphisms (SNPs) in 296 genes in a discovery phase using data from a genome-wide association study of EOC among women of European ancestry (1,947 cases and 2,009 controls) and identified 793 variants in 278 EMT-related genes that were nominally (P < 0.05) associated with invasive EOC. These SNPs were then genotyped in a larger study of 14,525 invasive-cancer patients and 23,447 controls. A P-value
Published: 2015

23. Common variants at the CHEK2 gene locus and risk of epithelial ovarian cancer

Author: Lawrenson, Kate, Iversen, Edwin S, Tyrer, Jonathan, Weber, Rachel Palmieri, Concannon, Patrick, Hazelett, Dennis J, Li, Qiyuan, Marks, Jeffrey R, Berchuck, Andrew, Lee, Janet M, Aben, Katja KH, Anton-Culver, Hoda, Antonenkova, Natalia, Bandera, Elisa V, Bean, Yukie, Beckmann, Matthias W, Bisogna, Maria, Bjorge, Line, Bogdanova, Natalia, Brinton, Louise A, Brooks-Wilson, Angela, Bruinsma, Fiona, Butzow, Ralf, Campbell, Ian G, Carty, Karen, Chang-Claude, Jenny, Chenevix-Trench, Georgia, Chen, Ann, Chen, Zhihua, Cook, Linda S, Cramer, Daniel W, Cunningham, Julie M, Cybulski, Cezary, Plisiecka-Halasa, Joanna, Dennis, Joe, Dicks, Ed, Doherty, Jennifer A, Dörk, Thilo, du Bois, Andreas, Eccles, Diana, Easton, Douglas T, Edwards, Robert P, Eilber, Ursula, Ekici, Arif B, Fasching, Peter A, Fridley, Brooke L, Gao, Yu-Tang, Gentry-Maharaj, Aleksandra, Giles, Graham G, Glasspool, Rosalind, Goode, Ellen L, Goodman, Marc T, Gronwald, Jacek, Harter, Philipp, Hasmad, Hanis Nazihah, Hein, Alexander, Heitz, Florian, Hildebrandt, Michelle AT, Hillemanns, Peter, Hogdall, Estrid, Hogdall, Claus, Hosono, Satoyo, Jakubowska, Anna, Paul, James, Jensen, Allan, Karlan, Beth Y, Kjaer, Susanne Kruger, Kelemen, Linda E, Kellar, Melissa, Kelley, Joseph L, Kiemeney, Lambertus A, Krakstad, Camilla, Lambrechts, Diether, Lambrechts, Sandrina, Le, Nhu D, Lee, Alice W, Cannioto, Rikki, Leminen, Arto, Lester, Jenny, Levine, Douglas A, Liang, Dong, Lissowska, Jolanta, Lu, Karen, Lubinski, Jan, Lundvall, Lene, Massuger, Leon FAG, Matsuo, Keitaro, McGuire, Valerie, McLaughlin, John R, Nevanlinna, Heli, McNeish, Iain, Menon, Usha, Modugno, Francesmary, Moysich, Kirsten B, Narod, Steven A, Nedergaard, Lotte, Ness, Roberta B, Azmi, Mat Adenan Noor, Odunsi, Kunle, and Olson, Sara H
Subjects: Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Clinical Research, Biotechnology, Cancer, Human Genome, Ovarian Cancer, Prevention, Rare Diseases, Genetic Testing, Genetics, Aetiology, 2.1 Biological and endogenous factors, Carcinoma, Ovarian Epithelial, Case-Control Studies, Checkpoint Kinase 2, Female, Genetic Loci, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Neoplasms, Glandular and Epithelial, Ovarian Neoplasms, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Risk Factors, Australian Cancer Study, Australian Ovarian Cancer Study Group, Oncology & Carcinogenesis, Oncology and carcinogenesis
Abstract: Genome-wide association studies have identified 20 genomic regions associated with risk of epithelial ovarian cancer (EOC), but many additional risk variants may exist. Here, we evaluated associations between common genetic variants [single nucleotide polymorphisms (SNPs) and indels] in DNA repair genes and EOC risk. We genotyped 2896 common variants at 143 gene loci in DNA samples from 15 397 patients with invasive EOC and controls. We found evidence of associations with EOC risk for variants at FANCA, EXO1, E2F4, E2F2, CREB5 and CHEK2 genes (P ≤ 0.001). The strongest risk association was for CHEK2 SNP rs17507066 with serous EOC (P = 4.74 x 10(-7)). Additional genotyping and imputation of genotypes from the 1000 genomes project identified a slightly more significant association for CHEK2 SNP rs6005807 (r (2) with rs17507066 = 0.84, odds ratio (OR) 1.17, 95% CI 1.11-1.24, P = 1.1×10(-7)). We identified 293 variants in the region with likelihood ratios of less than 1:100 for representing the causal variant. Functional annotation identified 25 candidate SNPs that alter transcription factor binding sites within regulatory elements active in EOC precursor tissues. In The Cancer Genome Atlas dataset, CHEK2 gene expression was significantly higher in primary EOCs compared to normal fallopian tube tissues (P = 3.72×10(-8)). We also identified an association between genotypes of the candidate causal SNP rs12166475 (r (2) = 0.99 with rs6005807) and CHEK2 expression (P = 2.70×10(-8)). These data suggest that common variants at 22q12.1 are associated with risk of serous EOC and CHEK2 as a plausible target susceptibility gene.
Published: 2015

24. Network-Based Integration of GWAS and Gene Expression Identifies a HOX-Centric Network Associated with Serous Ovarian Cancer Risk.

Author: Kar, Siddhartha P, Tyrer, Jonathan P, Li, Qiyuan, Lawrenson, Kate, Aben, Katja KH, Anton-Culver, Hoda, Antonenkova, Natalia, Chenevix-Trench, Georgia, Australian Cancer Study, Australian Ovarian Cancer Study Group, Baker, Helen, Bandera, Elisa V, Bean, Yukie T, Beckmann, Matthias W, Berchuck, Andrew, Bisogna, Maria, Bjørge, Line, Bogdanova, Natalia, Brinton, Louise, Brooks-Wilson, Angela, Butzow, Ralf, Campbell, Ian, Carty, Karen, Chang-Claude, Jenny, Chen, Yian Ann, Chen, Zhihua, Cook, Linda S, Cramer, Daniel, Cunningham, Julie M, Cybulski, Cezary, Dansonka-Mieszkowska, Agnieszka, Dennis, Joe, Dicks, Ed, Doherty, Jennifer A, Dörk, Thilo, du Bois, Andreas, Dürst, Matthias, Eccles, Diana, Easton, Douglas F, Edwards, Robert P, Ekici, Arif B, Fasching, Peter A, Fridley, Brooke L, Gao, Yu-Tang, Gentry-Maharaj, Aleksandra, Giles, Graham G, Glasspool, Rosalind, Goode, Ellen L, Goodman, Marc T, Grownwald, Jacek, Harrington, Patricia, Harter, Philipp, Hein, Alexander, Heitz, Florian, Hildebrandt, Michelle AT, Hillemanns, Peter, Hogdall, Estrid, Hogdall, Claus K, Hosono, Satoyo, Iversen, Edwin S, Jakubowska, Anna, Paul, James, Jensen, Allan, Ji, Bu-Tian, Karlan, Beth Y, Kjaer, Susanne K, Kelemen, Linda E, Kellar, Melissa, Kelley, Joseph, Kiemeney, Lambertus A, Krakstad, Camilla, Kupryjanczyk, Jolanta, Lambrechts, Diether, Lambrechts, Sandrina, Le, Nhu D, Lee, Alice W, Lele, Shashi, Leminen, Arto, Lester, Jenny, Levine, Douglas A, Liang, Dong, Lissowska, Jolanta, Lu, Karen, Lubinski, Jan, Lundvall, Lene, Massuger, Leon, Matsuo, Keitaro, McGuire, Valerie, McLaughlin, John R, McNeish, Iain A, Menon, Usha, Modugno, Francesmary, Moysich, Kirsten B, Narod, Steven A, Nedergaard, Lotte, Ness, Roberta B, Nevanlinna, Heli, Odunsi, Kunle, Olson, Sara H, and Orlow, Irene
Subjects: Australian Cancer Study, Australian Ovarian Cancer Study Group, Humans, Cystadenocarcinoma, Serous, Ovarian Neoplasms, Genetic Predisposition to Disease, Nuclear Proteins, Transcription Factors, DNA, Neoplasm, Morbidity, Risk Factors, Gene Expression Regulation, Neoplastic, Genotype, Female, Genome-Wide Association Study, Global Health, Ovarian Cancer, Biotechnology, Cancer, Genetics, Rare Diseases, Prevention, Human Genome, 2.1 Biological and endogenous factors, Epidemiology, Medical and Health Sciences
Abstract: BackgroundGenome-wide association studies (GWAS) have so far reported 12 loci associated with serous epithelial ovarian cancer (EOC) risk. We hypothesized that some of these loci function through nearby transcription factor (TF) genes and that putative target genes of these TFs as identified by coexpression may also be enriched for additional EOC risk associations.MethodsWe selected TF genes within 1 Mb of the top signal at the 12 genome-wide significant risk loci. Mutual information, a form of correlation, was used to build networks of genes strongly coexpressed with each selected TF gene in the unified microarray dataset of 489 serous EOC tumors from The Cancer Genome Atlas. Genes represented in this dataset were subsequently ranked using a gene-level test based on results for germline SNPs from a serous EOC GWAS meta-analysis (2,196 cases/4,396 controls).ResultsGene set enrichment analysis identified six networks centered on TF genes (HOXB2, HOXB5, HOXB6, HOXB7 at 17q21.32 and HOXD1, HOXD3 at 2q31) that were significantly enriched for genes from the risk-associated end of the ranked list (P < 0.05 and FDR < 0.05). These results were replicated (P < 0.05) using an independent association study (7,035 cases/21,693 controls). Genes underlying enrichment in the six networks were pooled into a combined network.ConclusionWe identified a HOX-centric network associated with serous EOC risk containing several genes with known or emerging roles in serous EOC development.ImpactNetwork analysis integrating large, context-specific datasets has the potential to offer mechanistic insights into cancer susceptibility and prioritize genes for experimental characterization.
Published: 2015

25. Cis-eQTL analysis and functional validation of candidate susceptibility genes for high-grade serous ovarian cancer.

Author: Lawrenson, Kate, Li, Qiyuan, Kar, Siddhartha, Seo, Ji-Heui, Tyrer, Jonathan, Spindler, Tassja J, Lee, Janet, Chen, Yibu, Karst, Alison, Drapkin, Ronny, Aben, Katja KH, Anton-Culver, Hoda, Antonenkova, Natalia, Australian Ovarian Cancer Study Group, Baker, Helen, Bandera, Elisa V, Bean, Yukie, Beckmann, Matthias W, Berchuck, Andrew, Bisogna, Maria, Bjorge, Line, Bogdanova, Natalia, Brinton, Louise A, Brooks-Wilson, Angela, Bruinsma, Fiona, Butzow, Ralf, Campbell, Ian G, Carty, Karen, Chang-Claude, Jenny, Chenevix-Trench, Georgia, Chen, Anne, Chen, Zhihua, Cook, Linda S, Cramer, Daniel W, Cunningham, Julie M, Cybulski, Cezary, Dansonka-Mieszkowska, Agnieszka, Dennis, Joe, Dicks, Ed, Doherty, Jennifer A, Dörk, Thilo, du Bois, Andreas, Dürst, Matthias, Eccles, Diana, Easton, Douglas T, Edwards, Robert P, Eilber, Ursula, Ekici, Arif B, Fasching, Peter A, Fridley, Brooke L, Gao, Yu-Tang, Gentry-Maharaj, Aleksandra, Giles, Graham G, Glasspool, Rosalind, Goode, Ellen L, Goodman, Marc T, Grownwald, Jacek, Harrington, Patricia, Harter, Philipp, Hasmad, Hanis Nazihah, Hein, Alexander, Heitz, Florian, Hildebrandt, Michelle AT, Hillemanns, Peter, Hogdall, Estrid, Hogdall, Claus, Hosono, Satoyo, Iversen, Edwin S, Jakubowska, Anna, James, Paul, Jensen, Allan, Ji, Bu-Tian, Karlan, Beth Y, Kruger Kjaer, Susanne, Kelemen, Linda E, Kellar, Melissa, Kelley, Joseph L, Kiemeney, Lambertus A, Krakstad, Camilla, Kupryjanczyk, Jolanta, Lambrechts, Diether, Lambrechts, Sandrina, Le, Nhu D, Lee, Alice W, Lele, Shashi, Leminen, Arto, Lester, Jenny, Levine, Douglas A, Liang, Dong, Lissowska, Jolanta, Lu, Karen, Lubinski, Jan, Lundvall, Lene, Massuger, Leon FAG, Matsuo, Keitaro, McGuire, Valerie, McLaughlin, John R, Nevanlinna, Heli, McNeish, Ian, and Menon, Usha
Subjects: Australian Ovarian Cancer Study Group, Cell Line, Tumor, Humans, Neoplasms, Glandular and Epithelial, Ovarian Neoplasms, Genetic Predisposition to Disease, Homeodomain Proteins, Neoplasm Proteins, Gene Expression Regulation, Neoplastic, Protein Binding, Quantitative Trait Loci, Female, Nuchal Cord, Genetic Association Studies, Carcinoma, Ovarian Epithelial, Cell Line, Tumor, Neoplasms, Glandular and Epithelial, Gene Expression Regulation, Neoplastic, Carcinoma, Ovarian Epithelial, Rare Diseases, Prevention, Ovarian Cancer, Biotechnology, Human Genome, Cancer, Genetics, 2.1 Biological and endogenous factors
Abstract: Genome-wide association studies have reported 11 regions conferring risk of high-grade serous epithelial ovarian cancer (HGSOC). Expression quantitative trait locus (eQTL) analyses can identify candidate susceptibility genes at risk loci. Here we evaluate cis-eQTL associations at 47 regions associated with HGSOC risk (P≤10(-5)). For three cis-eQTL associations (P
Published: 2015

26. Genome-wide significant risk associations for mucinous ovarian carcinoma (vol 47, pg 888, 2015)

Author: Kelemen, Linda E, Lawrenson, Kate, Tyrer, Jonathan, Li, Qiyuan, Lee, Janet M, Seo, Ji-Heui, Phelan, Catherine M, Beesley, Jonathan, Chen, Xiaoqing, Spindler, Tassja J, Aben, Katja KH, Anton-Culver, Hoda, Antonenkova, Natalia, Baker, Helen, Bandera, Elisa V, Bean, Yukie, Beckmann, Matthias W, Bisogna, Maria, Bjorge, Line, Bogdanova, Natalia, Brinton, Louise A, Brooks-Wilson, Angela, Bruinsma, Fiona, Butzow, Ralf, Campbell, Ian G, Carty, Karen, Chang-Claude, Jenny, Chen, Y Ann, Chen, Zhihua, Cook, Linda S, Cramer, Daniel W, Cunningham, Julie M, Cybulski, Cezary, Dansonka-Mieszkowska, Agnieszka, Dennis, Joe, Dicks, Ed, Doherty, Jennifer A, Doerk, Thilo, du Bois, Andreas, Duerst, Matthias, Eccles, Diana, Easton, Douglas T, Edwards, Robert P, Eilber, Ursula, Ekici, Arif B, Engelholm, Svend Aage, Fasching, Peter A, Fridley, Brooke L, Gao, Yu-Tang, Gentry-Maharaj, Aleksandra, Giles, Graham G, Glasspool, Rosalind, Goode, Ellen L, Goodman, Marc T, Grownwald, Jacek, Harrington, Patricia, Harter, Philipp, Hasmad, Hanis Nazihah, Hein, Alexander, Heitz, Florian, Hildebrandt, Michelle AT, Hillemanns, Peter, Hogdall, Estrid, Hogdall, Claus, Hosono, Satoyo, Iversen, Edwin S, Jakubowska, Anna, Jensen, Allan, Ji, Bu-Tian, Karlan, Beth Y, Kellar, Melissa, Kelley, Joseph L, Kiemeney, Lambertus A, Krakstad, Camilla, Kjaer, Susanne K, Kupryjanczyk, Jolanta, Lambrechts, Diether, Lambrechts, Sandrina, Le, Nhu D, Lee, Alice W, Lele, Shashi, Leminen, Arto, Lester, Jenny, Levine, Douglas A, Liang, Dong, Lissowska, Jolanta, Lu, Karen, Lubinski, Jan, Lundvall, Lene, Massuger, Leon FAG, Matsuo, Keitaro, McGuire, Valerie, McLaughlin, John R, McNeish, Iain, Menon, Usha, Modugno, Francesmary, Moes-Sosnowska, Joanna, Moysich, Kirsten B, Narod, Steven A, and Nedergaard, Lotte
Subjects: Developmental Biology, Medical and Health Sciences, Biological Sciences
Published: 2015

27. Cell-type-specific enrichment of risk-associated regulatory elements at ovarian cancer susceptibility loci

Author: Coetzee, Simon G, Shen, Howard C, Hazelett, Dennis J, Lawrenson, Kate, Kuchenbaecker, Karoline, Tyrer, Jonathan, Rhie, Suhn K, Levanon, Keren, Karst, Alison, Drapkin, Ronny, Ramus, Susan J, Consortium, The Consortium of Investigators of Modifiers of BRCA1 2 The Ovarian Cancer Association, Couch, Fergus J, Offit, Kenneth, Chenevix-Trench, Georgia, Monteiro, Alvaro NA, Antoniou, Antonis, Freedman, Matthew, Coetzee, Gerhard A, Pharoah, Paul DP, Noushmehr, Houtan, Gayther, Simon A, Anton-Culver, Hoda, Antonenkova, Natalia, Baker, Helen, Bandera, Elisa V, Bean, Yukie, Beckmann, Matthias W, Berchuck, Andrew, Bisogna, Maria, Bjorge, Line, Bogdanova, Natalia, Brinton, Louise A, Brooks-Wilson, Angela, Bruinsma, Fiona, Butzow, Ralf, Campbell, Ian G, Carty, Karen, Chang-Claude, Jenny, Chen, Ann, Chen, Zhihua, Cook, Linda S, Cramer, Daniel W, Cunningham, Julie M, Cybulski, Cezary, Dansonka-Mieszkowska, Agnieszka, Dennis, Joe, Dicks, Ed, Doherty, Jennifer A, Dörk, Thilo, du Bois, Andreas, Dürst, Matthias, Eccles, Diana, Easton, Douglas F, Edwards, Robert P, Eilber, Ursula, Ekici, Arif B, Fasching, Peter A, Fridley, Brooke L, Gao, Yu-Tang, Gentry-Maharaj, Aleksandra, Giles, Graham G, Glasspool, Rosalind, Goode, Ellen L, Goodman, Marc T, Grownwald, Jacek, Harrington, Patricia, Harter, Philipp, Hasmad, Hanis Nazihah, Hein, Alexander, Heitz, Florian, Hildebrandt, Michelle AT, Hillemanns, Peter, Hogdall, Estrid, Hogdall, Claus, Hosono, Satoyo, Iversen, Edwin S, Jakubowska, Anna, James, Paul, Jensen, Allan, Ji, Bu-Tian, Karlan, Beth Y, Kjaer, Susanne Kruger, Kelemen, Linda E, Kellar, Melissa, Kelley, Joseph L, Kiemeney, Lambertus A, Krakstad, Camilla, Kupryjanczyk, Jolanta, Lambrechts, Diether, Lambrechts, Sandrina, Le, Nhu D, Lele, Shashi, Leminen, Arto, Lester, Jenny, Levine, Douglas A, Liang, Dong, and Lissowska, Jolanta
Subjects: Biological Sciences, Genetics, Rare Diseases, Prevention, Human Genome, Ovarian Cancer, Biotechnology, Cancer, 2.1 Biological and endogenous factors, Underpinning research, Aetiology, 1.1 Normal biological development and functioning, Chromatin, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Histones, Humans, Organ Specificity, Ovarian Neoplasms, Polymorphism, Single Nucleotide, Regulatory Sequences, Nucleic Acid, Ovarian Cancer Association Consortium, The Consortium of Investigators of Modifiers of BRCA1/2, Ovarian Cancer Association Consortium The Consortium of Investigators of Modifiers of BRCA1/2, Medical and Health Sciences, Genetics & Heredity
Abstract: Understanding the regulatory landscape of the human genome is a central question in complex trait genetics. Most single-nucleotide polymorphisms (SNPs) associated with cancer risk lie in non-protein-coding regions, implicating regulatory DNA elements as functional targets of susceptibility variants. Here, we describe genome-wide annotation of regions of open chromatin and histone modification in fallopian tube and ovarian surface epithelial cells (FTSECs, OSECs), the debated cellular origins of high-grade serous ovarian cancers (HGSOCs) and in endometriosis epithelial cells (EECs), the likely precursor of clear cell ovarian carcinomas (CCOCs). The regulatory architecture of these cell types was compared with normal human mammary epithelial cells and LNCaP prostate cancer cells. We observed similar positional patterns of global enhancer signatures across the three different ovarian cancer precursor cell types, and evidence of tissue-specific regulatory signatures compared to non-gynecological cell types. We found significant enrichment for risk-associated SNPs intersecting regulatory biofeatures at 17 known HGSOC susceptibility loci in FTSECs (P = 3.8 × 10(-30)), OSECs (P = 2.4 × 10(-23)) and HMECs (P = 6.7 × 10(-15)) but not for EECs (P = 0.45) or LNCaP cells (P = 0.88). Hierarchical clustering of risk SNPs conditioned on the six different cell types indicates FTSECs and OSECs are highly related (96% of samples using multi-scale bootstrapping) suggesting both cell types may be precursors of HGSOC. These data represent the first description of regulatory catalogues of normal precursor cells for different ovarian cancer subtypes, and provide unique insights into the tissue specific regulatory variation with respect to the likely functional targets of germline genetic susceptibility variants for ovarian cancer.
Published: 2015

28. Common Genetic Variation In Cellular Transport Genes and Epithelial Ovarian Cancer (EOC) Risk

Author: Chornokur, Ganna, Lin, Hui-Yi, Tyrer, Jonathan P, Lawrenson, Kate, Dennis, Joe, Amankwah, Ernest K, Qu, Xiaotao, Tsai, Ya-Yu, Jim, Heather SL, Chen, Zhihua, Chen, Ann Y, Permuth-Wey, Jennifer, Aben, Katja KH, Anton-Culver, Hoda, Antonenkova, Natalia, Bruinsma, Fiona, Bandera, Elisa V, Bean, Yukie T, Beckmann, Matthias W, Bisogna, Maria, Bjorge, Line, Bogdanova, Natalia, Brinton, Louise A, Brooks-Wilson, Angela, Bunker, Clareann H, Butzow, Ralf, Campbell, Ian G, Carty, Karen, Chang-Claude, Jenny, Cook, Linda S, Cramer, Daniel W, Cunningham, Julie M, Cybulski, Cezary, Dansonka-Mieszkowska, Agnieszka, du Bois, Andreas, Despierre, Evelyn, Dicks, Ed, Doherty, Jennifer A, Dörk, Thilo, Dürst, Matthias, Easton, Douglas F, Eccles, Diana M, Edwards, Robert P, Ekici, Arif B, Fasching, Peter A, Fridley, Brooke L, Gao, Yu-Tang, Gentry-Maharaj, Aleksandra, Giles, Graham G, Glasspool, Rosalind, Goodman, Marc T, Gronwald, Jacek, Harrington, Patricia, Harter, Philipp, Hein, Alexander, Heitz, Florian, Hildebrandt, Michelle AT, Hillemanns, Peter, Hogdall, Claus K, Hogdall, Estrid, Hosono, Satoyo, Jakubowska, Anna, Jensen, Allan, Ji, Bu-Tian, Karlan, Beth Y, Kelemen, Linda E, Kellar, Mellissa, Kiemeney, Lambertus A, Krakstad, Camilla, Kjaer, Susanne K, Kupryjanczyk, Jolanta, Lambrechts, Diether, Lambrechts, Sandrina, Le, Nhu D, Lee, Alice W, Lele, Shashi, Leminen, Arto, Lester, Jenny, Levine, Douglas A, Liang, Dong, Lim, Boon Kiong, Lissowska, Jolanta, Lu, Karen, Lubinski, Jan, Lundvall, Lene, Massuger, Leon FAG, Matsuo, Keitaro, McGuire, Valerie, McLaughlin, John R, McNeish, Iain, Menon, Usha, Milne, Roger L, Modugno, Francesmary, Moysich, Kirsten B, Ness, Roberta B, Nevanlinna, Heli, Eilber, Ursula, Odunsi, Kunle, Olson, Sara H, and Orlow, Irene
Subjects: Biological Sciences, Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Genetics, Cancer, Ovarian Cancer, Rare Diseases, 2.1 Biological and endogenous factors, Aetiology, Black or African American, Alleles, Asian, Biological Transport, Carcinoma, Ovarian Epithelial, Carrier Proteins, Case-Control Studies, Female, Genetic Association Studies, Genetic Predisposition to Disease, Genetic Variation, Humans, Neoplasms, Glandular and Epithelial, Odds Ratio, Ovarian Neoplasms, Polymorphism, Single Nucleotide, Risk, Georgia Chenevix-Trench, AOCS management group, General Science & Technology
Abstract: BackgroundDefective cellular transport processes can lead to aberrant accumulation of trace elements, iron, small molecules and hormones in the cell, which in turn may promote the formation of reactive oxygen species, promoting DNA damage and aberrant expression of key regulatory cancer genes. As DNA damage and uncontrolled proliferation are hallmarks of cancer, including epithelial ovarian cancer (EOC), we hypothesized that inherited variation in the cellular transport genes contributes to EOC risk.MethodsIn total, DNA samples were obtained from 14,525 case subjects with invasive EOC and from 23,447 controls from 43 sites in the Ovarian Cancer Association Consortium (OCAC). Two hundred seventy nine SNPs, representing 131 genes, were genotyped using an Illumina Infinium iSelect BeadChip as part of the Collaborative Oncological Gene-environment Study (COGS). SNP analyses were conducted using unconditional logistic regression under a log-additive model, and the FDR q
Published: 2015

29. Common Genetic Variation in Circadian Rhythm Genes and Risk of Epithelial Ovarian Cancer (EOC)

Author: Jim, Heather SL, Lin, Hui-Yi, Tyrer, Jonathan P, Lawrenson, Kate, Dennis, Joe, Chornokur, Ganna, Chen, Zhihua, Chen, Ann Y, Permuth-Wey, Jennifer, Aben, Katja KH, Anton-Culver, Hoda, Antonenkova, Natalia, Bruinsma, Fiona, Bandera, Elisa V, Bean, Yukie T, Beckmann, Matthias W, Bisogna, Maria, Bjorge, Line, Bogdanova, Natalia, Brinton, Louise A, Brooks-Wilson, Angela, Bunker, Clareann H, Butzow, Ralf, Campbell, Ian G, Carty, Karen, Chang-Claude, Jenny, Cook, Linda S, Cramer, Daniel W, Cunningham, Julie M, Cybulski, Cezary, Dansonka-Mieszkowska, Agnieszka, du Bois, Andreas, Despierre, Evelyn, Sieh, Weiva, Doherty, Jennifer A, Dörk, Thilo, Dürst, Matthias, Easton, Douglas F, Eccles, Diana M, Edwards, Robert P, Ekici, Arif B, Fasching, Peter A, Fridley, Brooke L, Gao, Yu-Tang, Gentry-Maharaj, Aleksandra, Giles, Graham G, Glasspool, Rosalind, Goodman, Marc T, Gronwald, Jacek, Harter, Philipp, Hasmad, Hanis N, Hein, Alexander, Heitz, Florian, Hildebrandt, Michelle AT, Hillemanns, Peter, Hogdall, Claus K, Hogdall, Estrid, Hosono, Satoyo, Iversen, Edwin S, Jakubowska, Anna, Jensen, Allan, Ji, Bu-Tian, Karlan, Beth Y, Kellar, Melissa, Kiemeney, Lambertus A, Krakstad, Camilla, Kjaer, Susanne K, Kupryjanczyk, Jolanta, Vierkant, Robert A, Lambrechts, Diether, Lambrechts, Sandrina, Le, Nhu D, Lee, Alice W, Lele, Shashi, Leminen, Arto, Lester, Jenny, Levine, Douglas A, Liang, Dong, Lim, Boon Kiong, Lissowska, Jolanta, Lu, Karen, Lubinski, Jan, Lundvall, Lene, Massuger, Leon FAG, Matsuo, Keitaro, McGuire, Valerie, McLaughlin, John R, McNeish, Ian, Menon, Usha, Milne, Roger L, Modugno, Francesmary, Thomsen, Lotte, Moysich, Kirsten B, Ness, Roberta B, Nevanlinna, Heli, Eilber, Ursula, Odunsi, Kunle, Olson, Sara H, Orlow, Irene, and Orsulic, Sandra
Subjects: Biological Sciences, Biomedical and Clinical Sciences, Genetics, Health Services and Systems, Health Sciences, Oncology and Carcinogenesis, Cancer, Orphan Drug, Prevention, Sleep Research, Rare Diseases, Ovarian Cancer, Aetiology, 2.1 Biological and endogenous factors, Georgia Chenevix-Trench on behalf of the AOCS management group 95, 96
Abstract: Disruption in circadian gene expression, whether due to genetic variation or environmental factors (e.g., light at night, shiftwork), is associated with increased incidence of breast, prostate, gastrointestinal and hematologic cancers and gliomas. Circadian genes are highly expressed in the ovaries where they regulate ovulation; circadian disruption is associated with several ovarian cancer risk factors (e.g., endometriosis). However, no studies have examined variation in germline circadian genes as predictors of ovarian cancer risk and invasiveness. The goal of the current study was to examine single nucleotide polymorphisms (SNPs) in circadian genes BMAL1, CRY2, CSNK1E, NPAS2, PER3, REV1 and TIMELESS and downstream transcription factors KLF10 and SENP3 as predictors of risk of epithelial ovarian cancer (EOC) and histopathologic subtypes. The study included a test set of 3,761 EOC cases and 2,722 controls and a validation set of 44,308 samples including 18,174 (10,316 serous) cases and 26,134 controls from 43 studies participating in the Ovarian Cancer Association Consortium (OCAC). Analysis of genotype data from 36 genotyped SNPs and 4600 imputed SNPs indicated that the most significant association was rs117104877 in BMAL1 (OR = 0.79, 95% CI = 0.68-0.90, p = 5.59 × 10-4]. Functional analysis revealed a significant down regulation of BMAL1 expression following cMYC overexpression and increasing transformation in ovarian surface epithelial (OSE) cells as well as alternative splicing of BMAL1 exons in ovarian and granulosa cells. These results suggest that variation in circadian genes, and specifically BMAL1, may be associated with risk of ovarian cancer, likely through disruption of hormonal pathways.
Published: 2015

30. Maintenance olaparib in patients with platinum-sensitive relapsed ovarian cancer: Outcomes by somatic and germline BRCA and other homologous recombination repair gene mutation status in the ORZORA trial

Author: Pignata, Sandro, Oza, Amit, Hall, Geoff, Pardo, Beatriz, Madry, Radoslaw, Cibula, David, Klat, Jaroslav, Montes Worboys, Ana, Glasspool, Rosalind, Colombo, Nicoletta, Pete, Imre, Herrero Ibáñez, Ana, Romeo Marín, Margarita, Ilieva, Rumyana, Timcheva, Constanta, Maio, Massimo di, Blakeley, Christopher, Taylor, Rosie, Barnicle, Alan, Clamp, Andrew, Pignata, S, Oza, A, Hall, G, Pardo, B, Madry, R, Cibula, D, Klat, J, Montes, A, Glasspool, R, Colombo, N, Pete, I, Herrero Ibáñez, A, Marín, M, Ilieva, R, Timcheva, C, Di Maio, M, Blakeley, C, Taylor, R, Barnicle, A, and Clamp, A
Subjects: Olaparib, Oncology, Maintenance, Ovarian cancer, BRCA mutation, Càncer d'ovari, Genetics, Obstetrics and Gynecology, HRR, Genètica
Abstract: Background: The open-label, single-arm, multicenter ORZORA trial (NCT02476968) evaluated the efficacy and safety of maintenance olaparib in patients with platinum-sensitive relapsed ovarian cancer (PSR OC) who had tumor BRCA mutations (BRCAm) of germline (g) or somatic (s) origin or non-BRCA homologous recombination repair mutations (HRRm) and were in response to their most recent platinum-based chemotherapy after ≥2 lines of treatment. Methods: Patients received maintenance olaparib capsules (400mg twice daily) until disease progression. Prospective central testing at screening determined tumor BRCAm status and subsequent testing determined gBRCAm or sBRCAm status. Patients with predefined non-BRCA HRRm were assigned to an exploratory cohort. The co-primary endpoints were investigator-assessed progression-free survival (PFS; modified Response Evaluation Criteria in Solid Tumors v1.1) in BRCAm and sBRCAm cohorts. Secondary endpoints included health-related quality of life (HRQoL) and tolerability. Results: 177 patients received olaparib. At the primary data cut-off (17 April 2020), the median follow-up for PFS in the BRCAm cohort was 22.3months. The median PFS (95% CI) in BRCAm, sBRCAm, gBRCAm and non-BRCA HRRm cohorts was 18.0 (14.3-22.1), 16.6 (12.4-22.2), 19.3 (14.3-27.6) and 16.4 (10.9-19.3) months, respectively. Most patients with BRCAm reported improvements (21.8%) or no change (68.7%) in HRQoL and the safety profile was as expected. Conclusions: Maintenance olaparib had similar clinical activity in PSR OC patients with sBRCAm and those with any BRCAm. Activity was also observed in patients with a non-BRCA HRRm. ORZORA further supports use of maintenance olaparib in all patients with BRCA-mutated, including sBRCA-mutated, PSR OC.
Published: 2023

31. Pathological chemotherapy response score is prognostic in tubo-ovarian high-grade serous carcinoma: A systematic review and meta-analysis of individual patient data

Author: Aggarwal, Simi, Bronger, Holger, Brown, Elizabeth B., Buck, Martin, Bukhari, Syed A., Coghlan, Edwina, Cope, Nichola, de Almeida, Michelle Samora, De Kroon, Cornelius D., Dean, Andrew, Devlin, Michael-John, Ditzel, Helena M., Drecoll, Enken, Ebata, Takahiro, Fagotti, Anna, Faruqi, Asma, Feeney, Laura, Gupta, Kavita, Harley, Ian, Inzani, Frediano, Jeyarajah, Arjun R., Koay, M.H. Eleanor, Kroep, Judith R., Lee, Jung-Yun, Leung, Yee, Lockley, Michelle, Loft, Alice R., MaGee, Daniel, Manchanda, Ranjit, McKenna, Sarah, Midha, Divya, Millan, David, Millar, Joanne, Miller, Rowan, Mohan, Ganendra R., Mughal, Sohail, Mukhopadhyay, Asima, Nicolau, Sergio Mancini, Nevin, James, Oakley, Abigail S., Quigley, Mary, Rai, Bhavana, Rajwanshi, Arvind, Salfinger, Stuart G., Scambia, Giovanni, Scatchard, Kate, Schmalfeldt, Barbara, Simcock, Bryony, Singh, Priya, Strickland, Kyle C., Suri, Vainta, Syed, Sheeba, Sykes, Peter, Tamura, Kenji, Tan, Adeline, Tan, Jason, Thompson, Emily, Tinker, Anna V., Trevisan, Georgia, Uyeda, Maria Gabriela Baumgarten Kuster, Vaughan, Michelle M., Weichert, Wilko, Williams, Anthony, Williams, Sarah, Yoshida, Hiroshi, Zorzato, Pier Carlo, Cohen, Paul A., Powell, Aime, Böhm, Steffen, Gilks, C. Blake, Stewart, Colin J.R., Meniawy, Tarek M., Bulsara, Max, Avril, Stefanie, Brockbank, Eleanor C., Bosse, Tjalling, de Azevedo Focchi, Gustavo Rubino, Ganesan, Raji, Glasspool, Rosalind M., Howitt, Brooke E., Kim, Hyun-Soo, Le, Nhu D., Mandalia, Trupti, McCluggage, W. Glenn, McNeish, Iain, Srinivasan, Radhika, Tan, Yun Yi, van der Griend, Rachael, Yunokawa, Mayu, Zannoni, Gian F., and Singh, Naveena
Published: 2019
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32. Consortium analysis of gene and gene-folate interactions in purine and pyrimidine metabolism pathways with ovarian carcinoma risk.

Author: Kelemen, Linda E, Terry, Kathryn L, Goodman, Marc T, Webb, Penelope M, Bandera, Elisa V, McGuire, Valerie, Rossing, Mary Anne, Wang, Qinggang, Dicks, Ed, Tyrer, Jonathan P, Song, Honglin, Kupryjanczyk, Jolanta, Dansonka-Mieszkowska, Agnieszka, Plisiecka-Halasa, Joanna, Timorek, Agnieszka, Menon, Usha, Gentry-Maharaj, Aleksandra, Gayther, Simon A, Ramus, Susan J, Narod, Steven A, Risch, Harvey A, McLaughlin, John R, Siddiqui, Nadeem, Glasspool, Rosalind, Paul, James, Carty, Karen, Gronwald, Jacek, Lubiński, Jan, Jakubowska, Anna, Cybulski, Cezary, Kiemeney, Lambertus A, Massuger, Leon FAG, van Altena, Anne M, Aben, Katja KH, Olson, Sara H, Orlow, Irene, Cramer, Daniel W, Levine, Douglas A, Bisogna, Maria, Giles, Graham G, Southey, Melissa C, Bruinsma, Fiona, Kjaer, Susanne K, Høgdall, Estrid, Jensen, Allan, Høgdall, Claus K, Lundvall, Lene, Engelholm, Svend-Aage, Heitz, Florian, du Bois, Andreas, Harter, Philipp, Schwaab, Ira, Butzow, Ralf, Nevanlinna, Heli, Pelttari, Liisa M, Leminen, Arto, Thompson, Pamela J, Lurie, Galina, Wilkens, Lynne R, Lambrechts, Diether, Van Nieuwenhuysen, Els, Lambrechts, Sandrina, Vergote, Ignace, Beesley, Jonathan, AOCS Study Group/ACS Investigators, Fasching, Peter A, Beckmann, Matthias W, Hein, Alexander, Ekici, Arif B, Doherty, Jennifer A, Wu, Anna H, Pearce, Celeste L, Pike, Malcolm C, Stram, Daniel, Chang-Claude, Jenny, Rudolph, Anja, Dörk, Thilo, Dürst, Matthias, Hillemanns, Peter, Runnebaum, Ingo B, Bogdanova, Natalia, Antonenkova, Natalia, Odunsi, Kunle, Edwards, Robert P, Kelley, Joseph L, Modugno, Francesmary, Ness, Roberta B, Karlan, Beth Y, Walsh, Christine, Lester, Jenny, Orsulic, Sandra, Fridley, Brooke L, Vierkant, Robert A, Cunningham, Julie M, Wu, Xifeng, Lu, Karen, Liang, Dong, Hildebrandt, Michelle AT, Weber, Rachel Palmieri, and Iversen, Edwin S
Subjects: AOCS Study Group/ACS Investigators, Humans, Carcinoma, Ovarian Neoplasms, Folic Acid Deficiency, Genetic Predisposition to Disease, Folic Acid, Dihydrouracil Dehydrogenase (NADP), Neoplasm Proteins, Diet, Multivariate Analysis, Risk Factors, Case-Control Studies, Energy Intake, Polymorphism, Single Nucleotide, Dietary Supplements, European Continental Ancestry Group, Female, Genome-Wide Association Study, Global Health, Case-control, Dihydropyrimidine dehydrogenase, Folate, Polymorphism, Serine hydroxymethyltransferase 1, Rare Diseases, Cancer, Ovarian Cancer, Genetics, Nutrition, 2.1 Biological and endogenous factors, Nutrition & Dietetics, Food Science, Food Sciences, Nutrition and Dietetics, Public Health and Health Services
Abstract: ScopeWe reevaluated previously reported associations between variants in pathways of one-carbon (1-C) (folate) transfer genes and ovarian carcinoma (OC) risk, and in related pathways of purine and pyrimidine metabolism, and assessed interactions with folate intake.Methods and resultsOdds ratios (OR) for 446 genetic variants were estimated among 13,410 OC cases and 22,635 controls, and among 2281 cases and 3444 controls with folate information. Following multiple testing correction, the most significant main effect associations were for dihydropyrimidine dehydrogenase (DPYD) variants rs11587873 (OR = 0.92; p = 6 × 10⁻⁵) and rs828054 (OR = 1.06; p = 1 × 10⁻⁴). Thirteen variants in the pyrimidine metabolism genes, DPYD, DPYS, PPAT, and TYMS, also interacted significantly with folate in a multivariant analysis (corrected p = 9.9 × 10⁻⁶) but collectively explained only 0.2% of OC risk. Although no other associations were significant after multiple testing correction, variants in SHMT1 in 1-C transfer, previously reported with OC, suggested lower risk at higher folate (p(interaction) = 0.03-0.006).ConclusionVariation in pyrimidine metabolism genes, particularly DPYD, which was previously reported to be associated with OC, may influence risk; however, stratification by folate intake is unlikely to modify disease risk appreciably in these women. SHMT1 SNP-by-folate interactions are plausible but require further validation. Polymorphisms in selected genes in purine metabolism were not associated with OC.
Published: 2014

33. Supplementary Data from Epithelial-to-Mesenchymal Transition Supports Ovarian Carcinosarcoma Tumorigenesis and Confers Sensitivity to Microtubule Targeting with Eribulin

Author: Ho, Gwo Yaw, primary, Kyran, Elizabeth L., primary, Bedo, Justin, primary, Wakefield, Matthew J., primary, Ennis, Darren P., primary, Mirza, Hasan B., primary, Vandenberg, Cassandra J., primary, Lieschke, Elizabeth, primary, Farrell, Andrew, primary, Hadla, Anthony, primary, Lim, Ratana, primary, Dall, Genevieve, primary, Vince, James E., primary, Chua, Ngee Kiat, primary, Kondrashova, Olga, primary, Upstill-Goddard, Rosanna, primary, Bailey, Ulla-Maja, primary, Dowson, Suzanne, primary, Roxburgh, Patricia, primary, Glasspool, Rosalind M., primary, Bryson, Gareth, primary, Biankin, Andrew V., primary, Cooke, Susanna L., primary, Ratnayake, Gayanie, primary, McNally, Orla, primary, Traficante, Nadia, primary, DeFazio, Anna, primary, Weroha, S. John, primary, Bowtell, David D., primary, McNeish, Iain A., primary, Papenfuss, Anthony T., primary, Scott, Clare L., primary, and Barker, Holly E., primary
Published: 2023
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34. Data from Epithelial-to-Mesenchymal Transition Supports Ovarian Carcinosarcoma Tumorigenesis and Confers Sensitivity to Microtubule Targeting with Eribulin

Author: Ho, Gwo Yaw, primary, Kyran, Elizabeth L., primary, Bedo, Justin, primary, Wakefield, Matthew J., primary, Ennis, Darren P., primary, Mirza, Hasan B., primary, Vandenberg, Cassandra J., primary, Lieschke, Elizabeth, primary, Farrell, Andrew, primary, Hadla, Anthony, primary, Lim, Ratana, primary, Dall, Genevieve, primary, Vince, James E., primary, Chua, Ngee Kiat, primary, Kondrashova, Olga, primary, Upstill-Goddard, Rosanna, primary, Bailey, Ulla-Maja, primary, Dowson, Suzanne, primary, Roxburgh, Patricia, primary, Glasspool, Rosalind M., primary, Bryson, Gareth, primary, Biankin, Andrew V., primary, Cooke, Susanna L., primary, Ratnayake, Gayanie, primary, McNally, Orla, primary, Traficante, Nadia, primary, DeFazio, Anna, primary, Weroha, S. John, primary, Bowtell, David D., primary, McNeish, Iain A., primary, Papenfuss, Anthony T., primary, Scott, Clare L., primary, and Barker, Holly E., primary
Published: 2023
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35. #402 Implementation of scottish national ovarian cancer quality performance indicators – the process and the outcomes

Author: Mccormick, Aiste, primary, Burton, Kevin, additional, Martin, Cameron, additional, Gurumurthy, Mahalakshmi, additional, Cairns, Mary, additional, and Glasspool, Rosalind, additional
Published: 2023
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36. Identification and molecular characterization of a new ovarian cancer susceptibility locus at 17q21.31

Author: Permuth-Wey, Jennifer, Lawrenson, Kate, Shen, Howard C, Velkova, Aneliya, Tyrer, Jonathan P, Chen, Zhihua, Lin, Hui-Yi, Ann Chen, Y, Tsai, Ya-Yu, Qu, Xiaotao, Ramus, Susan J, Karevan, Rod, Lee, Janet, Lee, Nathan, Larson, Melissa C, Aben, Katja K, Anton-Culver, Hoda, Antonenkova, Natalia, Antoniou, Antonis C, Armasu, Sebastian M, Bacot, François, Baglietto, Laura, Bandera, Elisa V, Barnholtz-Sloan, Jill, Beckmann, Matthias W, Birrer, Michael J, Bloom, Greg, Bogdanova, Natalia, Brinton, Louise A, Brooks-Wilson, Angela, Brown, Robert, Butzow, Ralf, Cai, Qiuyin, Campbell, Ian, Chang-Claude, Jenny, Chanock, Stephen, Chenevix-Trench, Georgia, Cheng, Jin Q, Cicek, Mine S, Coetzee, Gerhard A, Cook, Linda S, Couch, Fergus J, Cramer, Daniel W, Cunningham, Julie M, Dansonka-Mieszkowska, Agnieszka, Despierre, Evelyn, Doherty, Jennifer A, Dörk, Thilo, du Bois, Andreas, Dürst, Matthias, Easton, Douglas F, Eccles, Diana, Edwards, Robert, Ekici, Arif B, Fasching, Peter A, Fenstermacher, David A, Flanagan, James M, Garcia-Closas, Montserrat, Gentry-Maharaj, Aleksandra, Giles, Graham G, Glasspool, Rosalind M, Gonzalez-Bosquet, Jesus, Goodman, Marc T, Gore, Martin, Górski, Bohdan, Gronwald, Jacek, Hall, Per, Halle, Mari K, Harter, Philipp, Heitz, Florian, Hillemanns, Peter, Hoatlin, Maureen, Høgdall, Claus K, Høgdall, Estrid, Hosono, Satoyo, Jakubowska, Anna, Jensen, Allan, Jim, Heather, Kalli, Kimberly R, Karlan, Beth Y, Kaye, Stanley B, Kelemen, Linda E, Kiemeney, Lambertus A, Kikkawa, Fumitaka, Konecny, Gottfried E, Krakstad, Camilla, Krüger Kjaer, Susanne, Kupryjanczyk, Jolanta, Lambrechts, Diether, Lambrechts, Sandrina, Lancaster, Johnathan M, Le, Nhu D, Leminen, Arto, Levine, Douglas A, Liang, Dong, Kiong Lim, Boon, Lin, Jie, Lissowska, Jolanta, Lu, Karen H, and Lubiński, Jan
Subjects: Biological Sciences, Biomedical and Clinical Sciences, Genetics, Rare Diseases, Biotechnology, Ovarian Cancer, Cancer, Human Genome, 2.1 Biological and endogenous factors, Aetiology, Carcinoma, Ovarian Epithelial, Chromosomes, Human, Pair 17, Female, Genetic Predisposition to Disease, Humans, Neoplasms, Glandular and Epithelial, Ovarian Neoplasms, Polymorphism, Single Nucleotide, Australian Cancer Study, Australian Ovarian Cancer Study, Consortium of Investigators of Modifiers of BRCA1/2
Abstract: Epithelial ovarian cancer (EOC) has a heritable component that remains to be fully characterized. Most identified common susceptibility variants lie in non-protein-coding sequences. We hypothesized that variants in the 3' untranslated region at putative microRNA (miRNA)-binding sites represent functional targets that influence EOC susceptibility. Here, we evaluate the association between 767 miRNA-related single-nucleotide polymorphisms (miRSNPs) and EOC risk in 18,174 EOC cases and 26,134 controls from 43 studies genotyped through the Collaborative Oncological Gene-environment Study. We identify several miRSNPs associated with invasive serous EOC risk (odds ratio=1.12, P=10(-8)) mapping to an inversion polymorphism at 17q21.31. Additional genotyping of non-miRSNPs at 17q21.31 reveals stronger signals outside the inversion (P=10(-10)). Variation at 17q21.31 is associated with neurological diseases, and our collaboration is the first to report an association with EOC susceptibility. An integrated molecular analysis in this region provides evidence for ARHGAP27 and PLEKHM1 as candidate EOC susceptibility genes.
Published: 2013

37. Efficacy and Safety of Weekly Paclitaxel Plus Vistusertib vs Paclitaxel Alone in Patients With Platinum-Resistant Ovarian High-Grade Serous Carcinoma

Author: Banerjee, Susana, primary, Giannone, Gaia, additional, Clamp, Andrew R., additional, Ennis, Darren P., additional, Glasspool, Rosalind M., additional, Herbertson, Rebecca, additional, Krell, Jonathan, additional, Riisnaes, Ruth, additional, Mirza, Hasan B., additional, Cheng, Zhao, additional, McDermott, Jacqueline, additional, Green, Clare, additional, Kristeleit, Rebecca S., additional, George, Angela, additional, Gourley, Charlie, additional, Lewsley, Liz-Anne, additional, Rai, Debbie, additional, Banerji, Udai, additional, Hinsley, Samantha, additional, and McNeish, Iain A., additional
Published: 2023
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38. The transcriptional regulation of telomerase

Author: Glasspool, Rosalind M.
Subjects: 616.994042
Published: 2003

39. Analysis of Anxiety, Depression and Fear of Progression at 12 Months Post-Cytoreductive Surgery in the SOCQER-2 (Surgery in Ovarian Cancer—Quality of Life Evaluation Research) Prospective, International, Multicentre Study.

Author: Lakhiani, Aarti, Cummins, Carole, Kumar, Satyam, Long, Joanna, Arora, Vivek, Balega, Janos, Broadhead, Tim, Duncan, Timothy, Edmondson, Richard, Fotopoulou, Christina, Glasspool, Rosalind, Kolomainen, Desiree, Manchanda, Ranjit, McNally, Orla, Morrison, Jo, Mukhopadhyay, Asima, Naik, Raj, Wood, Nick, and Sundar, Sudha
Subjects: DISEASE progression, RESEARCH, CANCER patient psychology, OVARIAN tumors, FEAR, MENTAL health, ATTITUDES toward illness, PATIENTS' attitudes, TUMOR classification, TREATMENT effectiveness, MENTAL depression, QUALITY of life, POSTOPERATIVE period, DISEASE prevalence, QUESTIONNAIRES, DESCRIPTIVE statistics, ANXIETY, CYTOREDUCTIVE surgery, BODY mass index, LONGITUDINAL method
Abstract: Simple Summary: Anxiety, depression and fear of cancer progression are common psychological challenges faced by women with ovarian cancer. It can affect a person's well-being, treatment compliance and quality of life. In this study, we assessed how often and how severe these concerns are 12 months after surgical treatment and if there is any association with surgical, patient and tumour factors. A total of 141 patients with advanced ovarian cancer who did not have disease progression at 12 months post-surgery completed two questionnaires. We found that a significant proportion of patients undergoing surgery for ovarian cancer experience anxiety, depression and fear of progression. It was not possible to identify a group of patients who are more affected by anxiety, depression or fear of progression. It is essential for healthcare providers to be attentive to the emotional needs of all ovarian cancer patients and provide appropriate support to help them cope with these psychological concerns effectively. Patients with ovarian cancer (OC) often experience anxiety, depression and fear of progression (FOP); however, it is unclear whether surgical complexity has a role to play. We investigated the prevalence of anxiety, depression and FOP at 12 months post-cytoreductive surgery and investigated associations with surgical complexity, patient (age, ethnicity, performance status, BMI) and tumour (stage, disease load) factors. One hundred and forty-one patients with FIGO Stage III–IV OC, who did not have disease progression at 12 months post-surgery, completed the Hospital Anxiety and Depression Scale and FOP short-form questionnaire. Patients underwent surgery with low (40.4%), intermediate (31.2%) and high (28.4%) surgical complexity scores. At 12 months post-surgery, 99 of 141 (70%) patients with advanced OC undergoing surgery experienced clinically significant anxiety, 21 of 141 (14.9%) patients experienced moderate to severe depression and 37 of 140 (26.4%) experienced dysfunctional FOP. No associations were identified between the three different surgical complexity groups with regards to anxiety, depression or FOP scores. Unsurprisingly, given the natural history of the disease, most patients with OC suffer from anxiety, depression and fear of progression after completion of first-line cancer treatment. Surgical complexity at the time of surgery is not associated with a deleterious impact on anxiety, depression or FOP for patients with OC. Patients with OC experience a profound mental health impact and should be offered mental health support throughout their cancer journey. [ABSTRACT FROM AUTHOR]
Published: 2024
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40. Real world outcomes in platinum sensitive relapsed ovarian, fallopian tube, or peritoneal cancer treated in routine clinical practice in the United Kingdom prior to poly-ADP ribose polymerase inhibitors

Author: Lord, Rosemary, Rauniyar, Jyoti, Morris, Tamsin, Condon, Orlaith, Jones, Rachel, Miller, Rowan, Hall, Marcia, Lofts, Fiona, Glasspool, Rosalind M, and Hudson, Emma
Published: 2020
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41. European Network of Gynaecological Oncological Trial Groupsʼ requirements for trials between academic groups and industry partners - a new Model D for drug and medical device development

Author: Concin, Nicole, Ray-Coquard, Isabelle, Glasspool, Rosalind M, Braicu, Elena, Farrelly, Laura, Votan, Benedicte, Mirza, Mansoor Raza, Martin, Antonio Gonzalez, Vergote, Ignace, and Pignata, Sandro
Published: 2020
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42. European Menopause and Andropause Society (EMAS) and International Gynecologic Cancer Society (IGCS) position statement on managing the menopause after gynecological cancer: focus on menopausal symptoms and osteoporosis

Author: Rees, Margaret, Angioli, Roberto, Coleman, Robert L, Glasspool, Rosalind M, Plotti, Francesco, Simoncini, Tommaso, and Terranova, Corrado
Published: 2020
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43. Copy number signatures and mutational processes in ovarian carcinoma

Author: Macintyre, Geoff, Goranova, Teodora E., De Silva, Dilrini, Ennis, Darren, Piskorz, Anna M., Eldridge, Matthew, Sie, Daoud, Lewsley, Liz-Anne, Hanif, Aishah, Wilson, Cheryl, Dowson, Suzanne, Glasspool, Rosalind M., Lockley, Michelle, Brockbank, Elly, Montes, Ana, Walther, Axel, Sundar, Sudha, Edmondson, Richard, Hall, Geoff D., Clamp, Andrew, Gourley, Charlie, Hall, Marcia, Fotopoulou, Christina, Gabra, Hani, Paul, James, Supernat, Anna, Millan, David, Hoyle, Aoisha, Bryson, Gareth, Nourse, Craig, Mincarelli, Laura, Sanchez, Luis Navarro, Ylstra, Bauke, Jimenez-Linan, Mercedes, Moore, Luiza, Hofmann, Oliver, Markowetz, Florian, McNeish, Iain A., and Brenton, James D.
Published: 2018
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44. Table S5 from Structural Variants at the BRCA1/2 Loci are a Common Source of Homologous Repair Deficiency in High-grade Serous Ovarian Carcinoma

Author: Ewing, Ailith, primary, Meynert, Alison, primary, Churchman, Michael, primary, Grimes, Graeme R., primary, Hollis, Robert L., primary, Herrington, C. Simon, primary, Rye, Tzyvia, primary, Bartos, Clare, primary, Croy, Ian, primary, Ferguson, Michelle, primary, Lennie, Mairi, primary, McGoldrick, Trevor, primary, McPhail, Neil, primary, Siddiqui, Nadeem, primary, Dowson, Suzanne, primary, Glasspool, Rosalind, primary, Mackean, Melanie, primary, Nussey, Fiona, primary, McDade, Brian, primary, Ennis, Darren, primary, McMahon, Lynn, primary, Matakidou, Athena, primary, Dougherty, Brian, primary, March, Ruth, primary, Barrett, J. Carl, primary, McNeish, Iain A., primary, Biankin, Andrew V., primary, Roxburgh, Patricia, primary, Gourley, Charlie, primary, and Semple, Colin A., primary
Published: 2023
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45. Table S7 from The Driver Mutational Landscape of Ovarian Squamous Cell Carcinomas Arising in Mature Cystic Teratoma

Author: Cooke, Susanna L., primary, Ennis, Darren, primary, Evers, Lisa, primary, Dowson, Suzanne, primary, Chan, Mei Yen, primary, Paul, James, primary, Hirschowitz, Lynn, primary, Glasspool, Rosalind M., primary, Singh, Naveena, primary, Bell, Sarah, primary, Day, Elizabeth, primary, Kochman, Agata, primary, Wilkinson, Nafisa, primary, Beer, Philip, primary, Martin, Sancha, primary, Millan, David, primary, Biankin, Andrew V., primary, and McNeish, Iain A., primary
Published: 2023
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46. Supplementary Information from Structural Variants at the BRCA1/2 Loci are a Common Source of Homologous Repair Deficiency in High-grade Serous Ovarian Carcinoma

Author: Ewing, Ailith, primary, Meynert, Alison, primary, Churchman, Michael, primary, Grimes, Graeme R., primary, Hollis, Robert L., primary, Herrington, C. Simon, primary, Rye, Tzyvia, primary, Bartos, Clare, primary, Croy, Ian, primary, Ferguson, Michelle, primary, Lennie, Mairi, primary, McGoldrick, Trevor, primary, McPhail, Neil, primary, Siddiqui, Nadeem, primary, Dowson, Suzanne, primary, Glasspool, Rosalind, primary, Mackean, Melanie, primary, Nussey, Fiona, primary, McDade, Brian, primary, Ennis, Darren, primary, McMahon, Lynn, primary, Matakidou, Athena, primary, Dougherty, Brian, primary, March, Ruth, primary, Barrett, J. Carl, primary, McNeish, Iain A., primary, Biankin, Andrew V., primary, Roxburgh, Patricia, primary, Gourley, Charlie, primary, and Semple, Colin A., primary
Published: 2023
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47. Figure S3 from The Driver Mutational Landscape of Ovarian Squamous Cell Carcinomas Arising in Mature Cystic Teratoma

Author: Cooke, Susanna L., primary, Ennis, Darren, primary, Evers, Lisa, primary, Dowson, Suzanne, primary, Chan, Mei Yen, primary, Paul, James, primary, Hirschowitz, Lynn, primary, Glasspool, Rosalind M., primary, Singh, Naveena, primary, Bell, Sarah, primary, Day, Elizabeth, primary, Kochman, Agata, primary, Wilkinson, Nafisa, primary, Beer, Philip, primary, Martin, Sancha, primary, Millan, David, primary, Biankin, Andrew V., primary, and McNeish, Iain A., primary
Published: 2023
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48. Data from Network-Based Integration of GWAS and Gene Expression Identifies a HOX-Centric Network Associated with Serous Ovarian Cancer Risk

Author: Kar, Siddhartha P., primary, Tyrer, Jonathan P., primary, Li, Qiyuan, primary, Lawrenson, Kate, primary, Aben, Katja K.H., primary, Anton-Culver, Hoda, primary, Antonenkova, Natalia, primary, Chenevix-Trench, Georgia, primary, Baker, Helen, primary, Bandera, Elisa V., primary, Bean, Yukie T., primary, Beckmann, Matthias W., primary, Berchuck, Andrew, primary, Bisogna, Maria, primary, Bjørge, Line, primary, Bogdanova, Natalia, primary, Brinton, Louise, primary, Brooks-Wilson, Angela, primary, Butzow, Ralf, primary, Campbell, Ian, primary, Carty, Karen, primary, Chang-Claude, Jenny, primary, Chen, Yian Ann, primary, Chen, Zhihua, primary, Cook, Linda S., primary, Cramer, Daniel, primary, Cunningham, Julie M., primary, Cybulski, Cezary, primary, Dansonka-Mieszkowska, Agnieszka, primary, Dennis, Joe, primary, Dicks, Ed, primary, Doherty, Jennifer A., primary, Dörk, Thilo, primary, du Bois, Andreas, primary, Dürst, Matthias, primary, Eccles, Diana, primary, Easton, Douglas F., primary, Edwards, Robert P., primary, Ekici, Arif B., primary, Fasching, Peter A., primary, Fridley, Brooke L., primary, Gao, Yu-Tang, primary, Gentry-Maharaj, Aleksandra, primary, Giles, Graham G., primary, Glasspool, Rosalind, primary, Goode, Ellen L., primary, Goodman, Marc T., primary, Grownwald, Jacek, primary, Harrington, Patricia, primary, Harter, Philipp, primary, Hein, Alexander, primary, Heitz, Florian, primary, Hildebrandt, Michelle A.T., primary, Hillemanns, Peter, primary, Hogdall, Estrid, primary, Hogdall, Claus K., primary, Hosono, Satoyo, primary, Iversen, Edwin S., primary, Jakubowska, Anna, primary, Paul, James, primary, Jensen, Allan, primary, Ji, Bu-Tian, primary, Karlan, Beth Y., primary, Kjaer, Susanne K., primary, Kelemen, Linda E., primary, Kellar, Melissa, primary, Kelley, Joseph, primary, Kiemeney, Lambertus A., primary, Krakstad, Camilla, primary, Kupryjanczyk, Jolanta, primary, Lambrechts, Diether, primary, Lambrechts, Sandrina, primary, Le, Nhu D., primary, Lee, Alice W., primary, Lele, Shashi, primary, Leminen, Arto, primary, Lester, Jenny, primary, Levine, Douglas A., primary, Liang, Dong, primary, Lissowska, Jolanta, primary, Lu, Karen, primary, Lubinski, Jan, primary, Lundvall, Lene, primary, Massuger, Leon, primary, Matsuo, Keitaro, primary, McGuire, Valerie, primary, McLaughlin, John R., primary, McNeish, Iain A., primary, Menon, Usha, primary, Modugno, Francesmary, primary, Moysich, Kirsten B., primary, Narod, Steven A., primary, Nedergaard, Lotte, primary, Ness, Roberta B., primary, Nevanlinna, Heli, primary, Odunsi, Kunle, primary, Olson, Sara H., primary, Orlow, Irene, primary, Orsulic, Sandra, primary, Weber, Rachel Palmieri, primary, Pearce, Celeste Leigh, primary, Pejovic, Tanja, primary, Pelttari, Liisa M., primary, Permuth-Wey, Jennifer, primary, Phelan, Catherine M., primary, Pike, Malcolm C., primary, Poole, Elizabeth M., primary, Ramus, Susan J., primary, Risch, Harvey A., primary, Rosen, Barry, primary, Rossing, Mary Anne, primary, Rothstein, Joseph H., primary, Rudolph, Anja, primary, Runnebaum, Ingo B., primary, Rzepecka, Iwona K., primary, Salvesen, Helga B., primary, Schildkraut, Joellen M., primary, Schwaab, Ira, primary, Shu, Xiao-Ou, primary, Shvetsov, Yurii B., primary, Siddiqui, Nadeem, primary, Sieh, Weiva, primary, Song, Honglin, primary, Southey, Melissa C., primary, Sucheston-Campbell, Lara E., primary, Tangen, Ingvild L., primary, Teo, Soo-Hwang, primary, Terry, Kathryn L., primary, Thompson, Pamela J., primary, Timorek, Agnieszka, primary, Tsai, Ya-Yu, primary, Tworoger, Shelley S., primary, van Altena, Anne M., primary, Van Nieuwenhuysen, Els, primary, Vergote, Ignace, primary, Vierkant, Robert A., primary, Wang-Gohrke, Shan, primary, Walsh, Christine, primary, Wentzensen, Nicolas, primary, Whittemore, Alice S., primary, Wicklund, Kristine G., primary, Wilkens, Lynne R., primary, Woo, Yin-Ling, primary, Wu, Xifeng, primary, Wu, Anna, primary, Yang, Hannah, primary, Zheng, Wei, primary, Ziogas, Argyrios, primary, Sellers, Thomas A., primary, Monteiro, Alvaro N.A., primary, Freedman, Matthew L., primary, Gayther, Simon A., primary, and Pharoah, Paul D.P., primary
Published: 2023
Full Text: View/download PDF

49. Supplementary Tables S1-6, Figures S1-2 from Network-Based Integration of GWAS and Gene Expression Identifies a HOX-Centric Network Associated with Serous Ovarian Cancer Risk

Author: Kar, Siddhartha P., primary, Tyrer, Jonathan P., primary, Li, Qiyuan, primary, Lawrenson, Kate, primary, Aben, Katja K.H., primary, Anton-Culver, Hoda, primary, Antonenkova, Natalia, primary, Chenevix-Trench, Georgia, primary, Baker, Helen, primary, Bandera, Elisa V., primary, Bean, Yukie T., primary, Beckmann, Matthias W., primary, Berchuck, Andrew, primary, Bisogna, Maria, primary, Bjørge, Line, primary, Bogdanova, Natalia, primary, Brinton, Louise, primary, Brooks-Wilson, Angela, primary, Butzow, Ralf, primary, Campbell, Ian, primary, Carty, Karen, primary, Chang-Claude, Jenny, primary, Chen, Yian Ann, primary, Chen, Zhihua, primary, Cook, Linda S., primary, Cramer, Daniel, primary, Cunningham, Julie M., primary, Cybulski, Cezary, primary, Dansonka-Mieszkowska, Agnieszka, primary, Dennis, Joe, primary, Dicks, Ed, primary, Doherty, Jennifer A., primary, Dörk, Thilo, primary, du Bois, Andreas, primary, Dürst, Matthias, primary, Eccles, Diana, primary, Easton, Douglas F., primary, Edwards, Robert P., primary, Ekici, Arif B., primary, Fasching, Peter A., primary, Fridley, Brooke L., primary, Gao, Yu-Tang, primary, Gentry-Maharaj, Aleksandra, primary, Giles, Graham G., primary, Glasspool, Rosalind, primary, Goode, Ellen L., primary, Goodman, Marc T., primary, Grownwald, Jacek, primary, Harrington, Patricia, primary, Harter, Philipp, primary, Hein, Alexander, primary, Heitz, Florian, primary, Hildebrandt, Michelle A.T., primary, Hillemanns, Peter, primary, Hogdall, Estrid, primary, Hogdall, Claus K., primary, Hosono, Satoyo, primary, Iversen, Edwin S., primary, Jakubowska, Anna, primary, Paul, James, primary, Jensen, Allan, primary, Ji, Bu-Tian, primary, Karlan, Beth Y., primary, Kjaer, Susanne K., primary, Kelemen, Linda E., primary, Kellar, Melissa, primary, Kelley, Joseph, primary, Kiemeney, Lambertus A., primary, Krakstad, Camilla, primary, Kupryjanczyk, Jolanta, primary, Lambrechts, Diether, primary, Lambrechts, Sandrina, primary, Le, Nhu D., primary, Lee, Alice W., primary, Lele, Shashi, primary, Leminen, Arto, primary, Lester, Jenny, primary, Levine, Douglas A., primary, Liang, Dong, primary, Lissowska, Jolanta, primary, Lu, Karen, primary, Lubinski, Jan, primary, Lundvall, Lene, primary, Massuger, Leon, primary, Matsuo, Keitaro, primary, McGuire, Valerie, primary, McLaughlin, John R., primary, McNeish, Iain A., primary, Menon, Usha, primary, Modugno, Francesmary, primary, Moysich, Kirsten B., primary, Narod, Steven A., primary, Nedergaard, Lotte, primary, Ness, Roberta B., primary, Nevanlinna, Heli, primary, Odunsi, Kunle, primary, Olson, Sara H., primary, Orlow, Irene, primary, Orsulic, Sandra, primary, Weber, Rachel Palmieri, primary, Pearce, Celeste Leigh, primary, Pejovic, Tanja, primary, Pelttari, Liisa M., primary, Permuth-Wey, Jennifer, primary, Phelan, Catherine M., primary, Pike, Malcolm C., primary, Poole, Elizabeth M., primary, Ramus, Susan J., primary, Risch, Harvey A., primary, Rosen, Barry, primary, Rossing, Mary Anne, primary, Rothstein, Joseph H., primary, Rudolph, Anja, primary, Runnebaum, Ingo B., primary, Rzepecka, Iwona K., primary, Salvesen, Helga B., primary, Schildkraut, Joellen M., primary, Schwaab, Ira, primary, Shu, Xiao-Ou, primary, Shvetsov, Yurii B., primary, Siddiqui, Nadeem, primary, Sieh, Weiva, primary, Song, Honglin, primary, Southey, Melissa C., primary, Sucheston-Campbell, Lara E., primary, Tangen, Ingvild L., primary, Teo, Soo-Hwang, primary, Terry, Kathryn L., primary, Thompson, Pamela J., primary, Timorek, Agnieszka, primary, Tsai, Ya-Yu, primary, Tworoger, Shelley S., primary, van Altena, Anne M., primary, Van Nieuwenhuysen, Els, primary, Vergote, Ignace, primary, Vierkant, Robert A., primary, Wang-Gohrke, Shan, primary, Walsh, Christine, primary, Wentzensen, Nicolas, primary, Whittemore, Alice S., primary, Wicklund, Kristine G., primary, Wilkens, Lynne R., primary, Woo, Yin-Ling, primary, Wu, Xifeng, primary, Wu, Anna, primary, Yang, Hannah, primary, Zheng, Wei, primary, Ziogas, Argyrios, primary, Sellers, Thomas A., primary, Monteiro, Alvaro N.A., primary, Freedman, Matthew L., primary, Gayther, Simon A., primary, and Pharoah, Paul D.P., primary
Published: 2023
Full Text: View/download PDF

50. Supplementary Figures 1-5, Tables 1-8 from Genome-wide Analysis Identifies Novel Loci Associated with Ovarian Cancer Outcomes: Findings from the Ovarian Cancer Association Consortium

Author: Johnatty, Sharon E., primary, Tyrer, Jonathan P., primary, Kar, Siddhartha, primary, Beesley, Jonathan, primary, Lu, Yi, primary, Gao, Bo, primary, Fasching, Peter A., primary, Hein, Alexander, primary, Ekici, Arif B., primary, Beckmann, Matthias W., primary, Lambrechts, Diether, primary, Van Nieuwenhuysen, Els, primary, Vergote, Ignace, primary, Lambrechts, Sandrina, primary, Rossing, Mary Anne, primary, Doherty, Jennifer A., primary, Chang-Claude, Jenny, primary, Modugno, Francesmary, primary, Ness, Roberta B., primary, Moysich, Kirsten B., primary, Levine, Douglas A., primary, Kiemeney, Lambertus A., primary, Massuger, Leon F.A.G., primary, Gronwald, Jacek, primary, Lubiński, Jan, primary, Jakubowska, Anna, primary, Cybulski, Cezary, primary, Brinton, Louise, primary, Lissowska, Jolanta, primary, Wentzensen, Nicolas, primary, Song, Honglin, primary, Rhenius, Valerie, primary, Campbell, Ian, primary, Eccles, Diana, primary, Sieh, Weiva, primary, Whittemore, Alice S., primary, McGuire, Valerie, primary, Rothstein, Joseph H., primary, Sutphen, Rebecca, primary, Anton-Culver, Hoda, primary, Ziogas, Argyrios, primary, Gayther, Simon A., primary, Gentry-Maharaj, Aleksandra, primary, Menon, Usha, primary, Ramus, Susan J., primary, Pearce, Celeste L., primary, Pike, Malcolm C., primary, Stram, Daniel O., primary, Wu, Anna H., primary, Kupryjanczyk, Jolanta, primary, Dansonka-Mieszkowska, Agnieszka, primary, Rzepecka, Iwona K., primary, Spiewankiewicz, Beata, primary, Goodman, Marc T., primary, Wilkens, Lynne R., primary, Carney, Michael E., primary, Thompson, Pamela J., primary, Heitz, Florian, primary, du Bois, Andreas, primary, Schwaab, Ira, primary, Harter, Philipp, primary, Pisterer, Jacobus, primary, Hillemanns, Peter, primary, Karlan, Beth Y., primary, Walsh, Christine, primary, Lester, Jenny, primary, Orsulic, Sandra, primary, Winham, Stacey J., primary, Earp, Madalene, primary, Larson, Melissa C., primary, Fogarty, Zachary C., primary, Høgdall, Estrid, primary, Jensen, Allan, primary, Kjaer, Susanne Kruger, primary, Fridley, Brooke L., primary, Cunningham, Julie M., primary, Vierkant, Robert A., primary, Schildkraut, Joellen M., primary, Iversen, Edwin S., primary, Terry, Kathryn L., primary, Cramer, Daniel W., primary, Bandera, Elisa V., primary, Orlow, Irene, primary, Pejovic, Tanja, primary, Bean, Yukie, primary, Høgdall, Claus, primary, Lundvall, Lene, primary, McNeish, Ian, primary, Paul, James, primary, Carty, Karen, primary, Siddiqui, Nadeem, primary, Glasspool, Rosalind, primary, Sellers, Thomas, primary, Kennedy, Catherine, primary, Chiew, Yoke-Eng, primary, Berchuck, Andrew, primary, MacGregor, Stuart, primary, Pharoah, Paul D.P., primary, Goode, Ellen L., primary, deFazio, Anna, primary, Webb, Penelope M., primary, and Chenevix-Trench, Georgia, primary
Published: 2023
Full Text: View/download PDF

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