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2. Autoantibodies, antigen-autoantibody complexes and antigens complement CA125 for early detection of ovarian cancer

Author

Young Han, Chae, Bedia, Jacob S., Yang, Wei-Lei, Hawley, Sarah J., Bergan, Lindsay, Hopper, Marika, Celestino, Joseph, Guo, Jing, Gornet, Terrie G., Soosaipillai, Antoninus, Yang, Hailing, Doskocil, Samantha D., Lokshin, Anna E., Handy, Beverly C., Diamandis, Eleftherios P., Moore, Richard G., Lu, Karen H., Lu, Zhen, Anderson, Karen S., Drescher, Charles W., Skates, Steven J., and Bast, Jr, Robert C.

Published
2024
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6. Measuring ovarian toxicity in clinical trials: an American Society of Clinical Oncology research statement

Author

Cui, Wanda, Rocconi, Rodney P, Thota, Ramya, Anderson, Richard A, Bruinooge, Suanna S, Comstock, Ioanna A, Denduluri, Neelima, Gassman, Audrey, Gralow, Julie, Hutt, Karla J, Amiri-Kordestani, Laleh, Lambertini, Matteo, Leighton, John, Lu, Karen H, Mostoufi-Moab, Sogol, Pollastro, Teri, Pradhan, Shan, Saber, Haleh, Schenkel, Caroline, Spratt, Daniel, Wedam, Suparna, and Phillips, Kelly-Anne

Published
2023
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7. 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

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. BRCA1 and BRCA2 pathogenic sequence variants in women of African origin or ancestry

Author

Friebel, Tara M, Andrulis, Irene L, Balmaña, Judith, Blanco, Amie M, Couch, Fergus J, Daly, Mary B, Domchek, Susan M, Easton, Douglas F, Foulkes, William D, Ganz, Patricia A, Garber, Judy, Glendon, Gord, Greene, Mark H, Hulick, Peter J, Isaacs, Claudine, Jankowitz, Rachel C, Karlan, Beth Y, Kirk, Judy, Kwong, Ava, Lee, Annette, Lesueur, Fabienne, Lu, Karen H, Nathanson, Katherine L, Neuhausen, Susan L, Offit, Kenneth, Palmero, Edenir I, Sharma, Priyanka, Tischkowitz, Marc, Toland, Amanda E, Tung, Nadine, van Rensburg, Elizabeth J, Vega, Ana, Weitzel, Jeffrey N, Collaborators, GEMO Study, Hoskins, Kent F, Maga, Tara, Parsons, Michael T, McGuffog, Lesley, Antoniou, Antonis C, Chenevix‐Trench, Georgia, Huo, Dezheng, Olopade, Olufunmilayo I, and Rebbeck, Timothy R

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Genetics, Breast Cancer, Cancer, Alleles, BRCA1 Protein, BRCA2 Protein, Black People, Female, Genetic Association Studies, Genetic Predisposition to Disease, Genetic Variation, Humans, Mutation, Population Surveillance, African ancestry, BRCA1, BRCA2, mutation, pathogenic sequence variant, Clinical Sciences, Genetics & Heredity, Clinical sciences
Abstract

BRCA1 and BRCA2 (BRCA1/2) pathogenic sequence variants (PSVs) confer elevated risks of multiple cancers. However, most BRCA1/2 PSVs reports focus on European ancestry individuals. Knowledge of the PSV distribution in African descent individuals is poorly understood. We undertook a systematic review of the published literature and publicly available databases reporting BRCA1/2 PSVs also accessed the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) database to identify African or African descent individuals. Using these data, we inferred which of the BRCA PSVs were likely to be of African continental origin. Of the 43,817 BRCA1/2 PSV carriers in the CIMBA database, 469 (1%) were of African descent. Additional African descent individuals were identified in public databases (n = 291) and the literature (n = 601). We identified 164 unique BRCA1 and 173 unique BRCA2 PSVs in individuals of African ancestry. Of these, 83 BRCA1 and 91 BRCA2 PSVs are of likely or possible African origin. We observed numerous differences in the distribution of PSV type and function in African origin versus non-African origin PSVs. Research in populations of African ancestry with BRCA1/2 PSVs is needed to provide the information needed for clinical management and decision-making in African descent individuals worldwide.

Published
2019

10. Mitochondrial defects and metabolic vulnerabilities in Lynch syndrome-associated MSH2-deficient endometrial cancer

Author

Bowen, Mikayla Borthwick, primary, Melendez, Brenda D, additional, Zhang, Qian, additional, Moreno, Diana, additional, Peralta, Leah, additional, Chan, Wai Kin, additional, Jeter, Collene, additional, Tan, Lin, additional, Zal, M. Anna, additional, Lorenzi, Philip L, additional, Dunner, Kenneth, additional, Yang, Richard K, additional, Broaddus, Russell R, additional, Celestino, Joseph, additional, Gokul, Nisha T, additional, Lu, Karen H, additional, Kim, Hyun-Eui, additional, Schmandt, Rosemarie, additional, and Yates, Melinda S, additional

Published
2024
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12. Clinical and genomic landscape of RAS mutations in gynecologic cancers

Author

Son, Ji, primary, Zhang, Yingao, additional, Lin, Heather, additional, Mirallas, Oriol, additional, Alvarez Ballesteros, Pablo, additional, Nardo, Mirella, additional, Clark, Natalie, additional, Hillman, R. Tyler, additional, Campbell, Erick, additional, Holla, Vijaykumar, additional, Johnson, Amber M., additional, Biter, Amadeo B., additional, Yuan, Ying, additional, Cobb, Lauren P., additional, Gershenson, David M., additional, Jazaeri, Amir A., additional, Lu, Karen H., additional, Soliman, Pamela T., additional, Westin, Shannon N., additional, Euscher, Elizabeth D., additional, Lawson, Barrett C., additional, Yang, Richard K., additional, Meric-Bernstam, Funda, additional, and Hong, David S., additional

Published
2024
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14. Polygenic risk modeling for prediction of epithelial ovarian cancer risk

Author

Dareng, Eileen O., Tyrer, Jonathan P., Barnes, Daniel R., Jones, Michelle R., Yang, Xin, Aben, Katja K. H., Adank, Muriel A., Agata, Simona, Andrulis, Irene L., Anton-Culver, Hoda, Antonenkova, Natalia N., Aravantinos, Gerasimos, Arun, Banu K., Augustinsson, Annelie, Balmaña, Judith, Bandera, Elisa V., Barkardottir, Rosa B., Barrowdale, Daniel, Beckmann, Matthias W., Beeghly-Fadiel, Alicia, Benitez, Javier, Bermisheva, Marina, Bernardini, Marcus Q., Bjorge, Line, Black, Amanda, Bogdanova, Natalia V., Bonanni, Bernardo, Borg, Ake, Brenton, James D., Budzilowska, Agnieszka, Butzow, Ralf, Buys, Saundra S., Cai, Hui, Caligo, Maria A., Campbell, Ian, Cannioto, Rikki, Cassingham, Hayley, Chang-Claude, Jenny, Chanock, Stephen J., Chen, Kexin, Chiew, Yoke-Eng, Chung, Wendy K., Claes, Kathleen B. M., Colonna, Sarah, Cook, Linda S., Couch, Fergus J., Daly, Mary B., Dao, Fanny, Davies, Eleanor, de la Hoya, Miguel, de Putter, Robin, Dennis, Joe, DePersia, Allison, Devilee, Peter, Diez, Orland, Ding, Yuan Chun, Doherty, Jennifer A., Domchek, Susan M., Dörk, Thilo, du Bois, Andreas, Dürst, Matthias, Eccles, Diana M., Eliassen, Heather A., Engel, Christoph, Evans, Gareth D., Fasching, Peter A., Flanagan, James M., Fortner, Renée T., Machackova, Eva, Friedman, Eitan, Ganz, Patricia A., Garber, Judy, Gensini, Francesca, Giles, Graham G., Glendon, Gord, Godwin, Andrew K., Goodman, Marc T., Greene, Mark H., Gronwald, Jacek, Hahnen, Eric, Haiman, Christopher A., Håkansson, Niclas, Hamann, Ute, Hansen, Thomas V. O., Harris, Holly R., Hartman, Mikael, Heitz, Florian, Hildebrandt, Michelle A. T., Høgdall, Estrid, Høgdall, Claus K., Hopper, John L., Huang, Ruea-Yea, Huff, Chad, Hulick, Peter J., Huntsman, David G., Imyanitov, Evgeny N., Isaacs, Claudine, Jakubowska, Anna, James, Paul A., Janavicius, Ramunas, Jensen, Allan, Johannsson, Oskar Th., John, Esther M., Jones, Michael E., Kang, Daehee, Karlan, Beth Y., Karnezis, Anthony, Kelemen, Linda E., Khusnutdinova, Elza, Kiemeney, Lambertus A., Kim, Byoung-Gie, Kjaer, Susanne K., Komenaka, Ian, Kupryjanczyk, Jolanta, Kurian, Allison W., Kwong, Ava, Lambrechts, Diether, Larson, Melissa C., Lazaro, Conxi, Le, Nhu D., Leslie, Goska, Lester, Jenny, Lesueur, Fabienne, Levine, Douglas A., Li, Lian, Li, Jingmei, Loud, Jennifer T., Lu, Karen H., Lubiński, Jan, Mai, Phuong L., Manoukian, Siranoush, Marks, Jeffrey R., Matsuno, Rayna Kim, Matsuo, Keitaro, May, Taymaa, McGuffog, Lesley, McLaughlin, John R., McNeish, Iain A., Mebirouk, Noura, Menon, Usha, Miller, Austin, Milne, Roger L., Minlikeeva, Albina, Modugno, Francesmary, Montagna, Marco, Moysich, Kirsten B., Munro, Elizabeth, Nathanson, Katherine L., Neuhausen, Susan L., Nevanlinna, Heli, Yie, Joanne Ngeow Yuen, Nielsen, Henriette Roed, Nielsen, Finn C., Nikitina-Zake, Liene, Odunsi, Kunle, Offit, Kenneth, Olah, Edith, Olbrecht, Siel, Olopade, Olufunmilayo I., Olson, Sara H., Olsson, Håkan, Osorio, Ana, Papi, Laura, Park, Sue K., Parsons, Michael T., Pathak, Harsha, Pedersen, Inge Sokilde, Peixoto, Ana, Pejovic, Tanja, Perez-Segura, Pedro, Permuth, Jennifer B., Peshkin, Beth, Peterlongo, Paolo, Piskorz, Anna, Prokofyeva, Darya, Radice, Paolo, Rantala, Johanna, Riggan, Marjorie J., Risch, Harvey A., Rodriguez-Antona, Cristina, Ross, Eric, Rossing, Mary Anne, Runnebaum, Ingo, Sandler, Dale P., Santamariña, Marta, Soucy, Penny, Schmutzler, Rita K., Setiawan, V. Wendy, Shan, Kang, Sieh, Weiva, Simard, Jacques, Singer, Christian F., Sokolenko, Anna P., Song, Honglin, Southey, Melissa C., Steed, Helen, Stoppa-Lyonnet, Dominique, Sutphen, Rebecca, Swerdlow, Anthony J., Tan, Yen Yen, Teixeira, Manuel R., Teo, Soo Hwang, Terry, Kathryn L., Terry, Mary Beth, Thomassen, Mads, Thompson, Pamela J., Thomsen, Liv Cecilie Vestrheim, Thull, Darcy L., Tischkowitz, Marc, Titus, Linda, Toland, Amanda E., Torres, Diana, Trabert, Britton, Travis, Ruth, Tung, Nadine, Tworoger, Shelley S., Valen, Ellen, van Altena, Anne M., van der Hout, Annemieke H., Van Nieuwenhuysen, Els, van Rensburg, Elizabeth J., Vega, Ana, Edwards, Digna Velez, Vierkant, Robert A., Wang, Frances, Wappenschmidt, Barbara, Webb, Penelope M., Weinberg, Clarice R., Weitzel, Jeffrey N., Wentzensen, Nicolas, White, Emily, Whittemore, Alice S., Winham, Stacey J., Wolk, Alicja, Woo, Yin-Ling, Wu, Anna H., Yan, Li, Yannoukakos, Drakoulis, Zavaglia, Katia M., Zheng, Wei, Ziogas, Argyrios, Zorn, Kristin K., Kleibl, Zdenek, Easton, Douglas, Lawrenson, Kate, DeFazio, Anna, Sellers, Thomas A., Ramus, Susan J., Pearce, Celeste L., Monteiro, Alvaro N., Cunningham, Julie, Goode, Ellen L., Schildkraut, Joellen M., Berchuck, Andrew, Chenevix-Trench, Georgia, Gayther, Simon A., Antoniou, Antonis C., and Pharoah, Paul D. P.

Published
2022
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17. 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, Women's Health, Cancer, Ovarian Cancer, Prevention, Rare Diseases, 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

19. List of contributors

Author

Advincula, Arnold P., primary, Bakkum-Gamez, Jamie N., additional, Bouchard-Fortier, Genevieve, additional, Burke, Anne, additional, Clark, Leslie H., additional, Coleman, Robert L., additional, Covens, Allan, additional, Cowley, Deborah S., additional, Davis, Anne R., additional, Dolan, Mary Segars, additional, Dotters-Katz, Sarah K., additional, Douglas, Nataki C., additional, Dowdy, Sean C., additional, Eckert, Linda O., additional, Fialkow, Michael, additional, Forman, Eric J., additional, Frumovitz, Michael, additional, Gehrig, Paola Alvarez, additional, Gershenson, David M., additional, Gilner, Jennifer Bushman, additional, Havrilesky, Laura J., additional, Hill, Cherie C., additional, Hur, Hye-Chun, additional, Jhingran, Anuja, additional, Kelley, James M., additional, Kirby, Anna C., additional, Kuller, Jeffrey A., additional, Lara-Torre, Eduardo, additional, Lentz, Gretchen M., additional, Lobo, Roger A., additional, Lu, Karen H., additional, Mendiratta, Vicki, additional, Meyer, Larissa A., additional, Miller, Jane L., additional, Nica, Andra, additional, Nunziato, Jaclyn D., additional, Orr, James W., additional, Padro, Amanda, additional, Phoolcharoen, Natacha, additional, Price, Thomas M., additional, Rackow, Beth W., additional, Ramirez, Pedro T., additional, Raymond, Licia, additional, Rhee, Eleanor H.J., additional, Rivlin, Katherine, additional, Rock, David T., additional, Ryntz, Timothy, additional, Salcedo, Mila Pontremoli, additional, Salvo, Gloria, additional, Sandadi, Samith, additional, Schmeler, Kathleen M., additional, Smith, Judith A., additional, Soliman, Pamela T., additional, Sood, Anil K., additional, Thaker, Premal H., additional, Truong, Mireille, additional, Turocy, Jenna, additional, Valea, Fidel A., additional, Watson, Catherine H., additional, Westin, Shannon N., additional, and Williams, Zev, additional

Published
2022
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20. Abstract A077: The utility of surgical minimal residual disease after frontline treatment for prognostic and investigational opportunities in advanced ovarian cancer

Author

Knisely, Anne, primary, Nitecki, Roni, additional, Rauh-Hain, J. Alejandro, additional, Hillman, R. Tyler, additional, Taylor, Jolyn S., additional, Ramondetta, Lois M., additional, Grinsfelder, Michaela O., additional, Cobb, Lauren P., additional, Boruta, David M., additional, Richardson, Gwyn, additional, Soliman, Pamela T., additional, Shafer, Aaron, additional, Westin, Shannon N., additional, Fleming, Nicole D., additional, Sims, Travis T., additional, Sood, Anil K., additional, Ramirez, Pedro T., additional, Lu, Karen H., additional, and Jazaeri, Amir A., additional

Published
2024
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23. Molecular, Metabolic, and Subcellular Mapping of the Tumor Immune Microenvironment via 3D Targeted and Non-Targeted Multiplex Multi-Omics Analyses

Author

Ferri-Borgogno, Sammy, primary, Burks, Jared K., additional, Seeley, Erin H., additional, McKee, Trevor D., additional, Stolley, Danielle L., additional, Basi, Akshay V., additional, Gomez, Javier A., additional, Gamal, Basant T., additional, Ayyadhury, Shamini, additional, Lawson, Barrett C., additional, Yates, Melinda S., additional, Birrer, Michael J., additional, Lu, Karen H., additional, and Mok, Samuel C., additional

Published
2024
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24. Efficacy and safety of autologous tumor-infiltrating lymphocytes in recurrent or refractory ovarian cancer, colorectal cancer, and pancreatic ductal adenocarcinoma

Author

Amaria, Rodabe, primary, Knisely, Anne, additional, Vining, David, additional, Kopetz, Scott, additional, Overman, Michael J, additional, Javle, Milind, additional, Antonoff, Mara B, additional, Tzeng, Ching-Wei D, additional, Wolff, Robert A, additional, Pant, Shubham, additional, Lito, Kathryn, additional, Rangel, Kelly, additional, Fellman, Bryan, additional, Yuan, Ying, additional, Lu, Karen H, additional, Sakellariou-Thompson, Donastas, additional, Haymaker, Cara L, additional, Forget, Marie-Andrée, additional, Hwu, Patrick, additional, Bernatchez, Chantale, additional, and Jazaeri, Amir A, additional

Published
2024
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25. Normal Risk Ovarian Screening Study: 21-Year Update

Author

Han, Chae Young, primary, Lu, Karen H., additional, Corrigan, Gwen, additional, Perez, Alexandra, additional, Kohring, Sharlene D., additional, Celestino, Joseph, additional, Bedi, Deepak, additional, Bedia, Enrique, additional, Bevers, Therese, additional, Boruta, David, additional, Carlson, Matthew, additional, Holman, Laura, additional, Leeds, Leroy, additional, Mathews, Cara, additional, McCann, Georgia, additional, Moore, Richard G., additional, Schlumbrecht, Matthew, additional, Slomovitz, Brian, additional, Tobias, Dan, additional, Williams-Brown, Yvette, additional, Bevers, Michael W., additional, Liu, Jinsong, additional, Gornet, Terrie G., additional, Handy, Beverly C., additional, Lu, Zhen, additional, Bedia, Jacob S., additional, Skates, Steven J., additional, and Bast, Robert C., additional

Published
2024
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26. Data from Experiences of Family Communication and Cascade Genetic Testing for Hereditary Cancer in Medically Underserved Populations—A Qualitative Study

Author

Bednar, Erica M., primary, Rauh-Hain, J. Alejandro, primary, Garcia, Jose J., primary, de Aguinaga, Norma, primary, Powell, Mary Anne, primary, Peral, Sylvia L., primary, Nitecki, Roni, primary, Jorgensen, Kirsten, primary, Rudy, Natasha L., primary, Lu, Karen H., primary, Leath, Charles A., primary, and Scarinci, Isabel C., primary

Published
2024
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27. Supplementary Table 1 from Experiences of Family Communication and Cascade Genetic Testing for Hereditary Cancer in Medically Underserved Populations—A Qualitative Study

Author

Bednar, Erica M., primary, Rauh-Hain, J. Alejandro, primary, Garcia, Jose J., primary, de Aguinaga, Norma, primary, Powell, Mary Anne, primary, Peral, Sylvia L., primary, Nitecki, Roni, primary, Jorgensen, Kirsten, primary, Rudy, Natasha L., primary, Lu, Karen H., primary, Leath, Charles A., primary, and Scarinci, Isabel C., primary

Published
2024
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28. Supplementary Materials and Methods 1 from Experiences of Family Communication and Cascade Genetic Testing for Hereditary Cancer in Medically Underserved Populations—A Qualitative Study

Author

Bednar, Erica M., primary, Rauh-Hain, J. Alejandro, primary, Garcia, Jose J., primary, de Aguinaga, Norma, primary, Powell, Mary Anne, primary, Peral, Sylvia L., primary, Nitecki, Roni, primary, Jorgensen, Kirsten, primary, Rudy, Natasha L., primary, Lu, Karen H., primary, Leath, Charles A., primary, and Scarinci, Isabel C., primary

Published
2024
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29. Phase 1b Study of Batiraxcept (AVB-S6-500) in Combination with Durvalumab (MEDI4736) in Patients with Platinum-Resistant Ovarian Cancer

Author

Knisely, Anne, primary, Hinchcliff, Emily M., additional, Gardiner, Elisabeth, additional, Rangwala, Reshma, additional, Lito, Kathryn, additional, Fellman, Bryan, additional, Yuan, Ying, additional, Sood, Anil, additional, Westin, Shannon N., additional, Lu, Karen H., additional, and Jazaeri, Amir A., additional

Published
2024
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30. Phase II Trial of Pembrolizumab in Combination with Chemotherapy for Frontline Treatment of Advanced Epithelial Ovarian Cancer

Author

How, Jeffrey Andrew, primary, Dang, Minghao, additional, Lee, Sanghoon, additional, Fellman, Bryan, additional, Westin, Shannon N., additional, Sood, Anil, additional, Fleming, Nicole D., additional, Shafer, Aaron, additional, Yuan, Ying, additional, Liu, Jinsong, additional, Zhao, Li, additional, Celestino, Joseph, additional, Hajek, Richard, additional, Morgan, Margaret B., additional, Parra, Edwin Roger, additional, Fernandez, Caddie D. Laberiano, additional, Arrechedera, Claudio A., additional, Solis, Luisa, additional, Schmeler, Kathleen, additional, Nick, Alpa, additional, Lu, Karen H., additional, Coleman, Robert, additional, Wang, Linghua, additional, and Jazaeri, Amir A., additional

Published
2024
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36. Clinical significance of homologous recombination deficiency score testing in endometrial Cancer

Author

Siedel, Jean H., Ring, Kari L., Hu, Wei, Dood, Robert L., Wang, Ying, Baggerly, Keith, Darcy, Kathleen M., Conrads, Thomas P., Gallagher, Shannon, Tshiaba, Placede, Neff, Chris, Timms, Kirsten M., Mangala, Selanere, Westin, Shannon N., Broaddus, Russell, Lopez-Berestein, Gabriel, Lu, Karen H., Coleman, Robert L., Maxwell, George L., and Sood, Anil K.

Published
2021
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37. Early Detection of Ovarian Cancer using the Risk of Ovarian Cancer Algorithm with Frequent CA125 Testing in Women at Increased Familial Risk – Combined Results from Two Screening Trials

Author

Skates, Steven J, Greene, Mark H, Buys, Saundra S, Mai, Phuong L, Brown, Powel, Piedmonte, Marion, Rodriguez, Gustavo, Schorge, John O, Sherman, Mark, Daly, Mary B, Rutherford, Thomas, Brewster, Wendy R, O'Malley, David M, Partridge, Edward, Boggess, John, Drescher, Charles W, Isaacs, Claudine, Berchuck, Andrew, Domchek, Susan, Davidson, Susan A, Edwards, Robert, Elg, Steven A, Wakeley, Katie, Phillips, Kelly-Anne, Armstrong, Deborah, Horowitz, Ira, Fabian, Carol J, Walker, Joan, Sluss, Patrick M, Welch, William, Minasian, Lori, Horick, Nora K, Kasten, Carol H, Nayfield, Susan, Alberts, David, Finkelstein, Dianne M, and Lu, Karen H

Subjects
Cancer, Ovarian Cancer, Prevention, Genetic Testing, Rare Diseases, Clinical Research, Genetics, Detection, screening and diagnosis, 4.4 Population screening, Adult, Aged, Algorithms, Breast Neoplasms, CA-125 Antigen, Early Detection of Cancer, Female, Humans, Membrane Proteins, Middle Aged, Neoplasm Staging, Ovarian Neoplasms, Risk Factors, Oncology and Carcinogenesis, Oncology & Carcinogenesis
Abstract

Purpose: Women at familial/genetic ovarian cancer risk often undergo screening despite unproven efficacy. Research suggests each woman has her own CA125 baseline; significant increases above this level may identify cancers earlier than standard 6- to 12-monthly CA125 > 35 U/mL.Experimental Design: Data from prospective Cancer Genetics Network and Gynecologic Oncology Group trials, which screened 3,692 women (13,080 woman-screening years) with a strong breast/ovarian cancer family history or BRCA1/2 mutations, were combined to assess a novel screening strategy. Specifically, serum CA125 q3 months, evaluated using a risk of ovarian cancer algorithm (ROCA), detected significant increases above each subject's baseline, which triggered transvaginal ultrasound. Specificity and positive predictive value (PPV) were compared with levels derived from general population screening (specificity 90%, PPV 10%), and stage-at-detection was compared with historical high-risk controls.Results: Specificity for ultrasound referral was 92% versus 90% (P = 0.0001), and PPV was 4.6% versus 10% (P > 0.10). Eighteen of 19 malignant ovarian neoplasms [prevalent = 4, incident = 6, risk-reducing salpingo-oophorectomy (RRSO) = 9] were detected via screening or RRSO. Among incident cases (which best reflect long-term screening performance), three of six invasive cancers were early-stage (I/II; 50% vs. 10% historical BRCA1 controls; P = 0.016). Six of nine RRSO-related cases were stage I. ROCA flagged three of six (50%) incident cases before CA125 exceeded 35 U/mL. Eight of nine patients with stages 0/I/II ovarian cancer were alive at last follow-up (median 6 years).Conclusions: For screened women at familial/genetic ovarian cancer risk, ROCA q3 months had better early-stage sensitivity at high specificity, and low yet possibly acceptable PPV compared with CA125 > 35 U/mL q6/q12 months, warranting further larger cohort evaluation. Clin Cancer Res; 23(14); 3628-37. ©2017 AACR.

Published
2017

38. Inherited variants affecting RNA editing may contribute to ovarian cancer susceptibility: results from a large-scale collaboration

Author

Permuth, Jennifer B, Reid, Brett, Earp, Madalene, Chen, Y Ann, Monteiro, Alvaro NA, Chen, Zhihua, Group, AOCS Study, Chenevix-Trench, Georgia, Fasching, Peter A, Beckmann, Matthias W, Lambrechts, Diether, Vanderstichele, Adriaan, Van Niewenhuyse, Els, Vergote, Ignace, Rossing, Mary Anne, Doherty, Jennifer Anne, Chang-Claude, Jenny, Moysich, Kirsten, Odunsi, Kunle, Goodman, Marc T, Shvetsov, Yurii B, Wilkens, Lynne R, Thompson, Pamela J, Dörk, Thilo, Bogdanova, Natalia, Butzow, Ralf, Nevanlinna, Heli, Pelttari, Liisa, Leminen, Arto, Modugno, Francesmary, Edwards, Robert P, Ness, Roberta B, Kelley, Joseph, Heitz, Florian, Karlan, Beth, Lester, Jenny, Kjaer, Susanne K, Jensen, Allan, Giles, Graham, Hildebrandt, Michelle, Liang, Dong, Lu, Karen H, Wu, Xifeng, Levine, Douglas A, Bisogna, Maria, Berchuck, Andrew, Cramer, Daniel W, Terry, Kathryn L, Tworoger, Shelley S, Poole, Elizabeth M, Bandera, Elisa V, Fridley, Brooke, Cunningham, Julie, Winham, Stacey J, Olson, Sara H, Orlow, Irene, Bjorge, Line, Kiemeney, Lambertus A, Massuger, Leon, Pejovic, Tanja, Moffitt, Melissa, Le, Nhu, Cook, Linda S, Brooks-Wilson, Angela, Kelemen, Linda E, Gronwald, Jacek, Lubinski, Jan, Wentzensen, Nicolas, Brinton, Louise A, Lissowska, Jolanta, Yang, Hanna, Hogdall, Estrid, Hogdall, Claus, Lundvall, Lene, Pharoah, Paul DP, Song, Honglin, Campbell, Ian, Eccles, Diana, McNeish, Iain, Whittemore, Alice, McGuire, Valerie, Sieh, Weiva, Rothstein, Joseph, Phelan, Catherine M, Risch, Harvey, Narod, Steven, McLaughlin, John, Anton-Culver, Hoda, Ziogas, Argyrios, Menon, Usha, Gayther, Simon, Ramus, Susan J, Gentry-Maharaj, Aleksandra, Pearce, Celeste Leigh, Wu, Anna H, Kupryjanczyk, Jolanta, Dansonka-Mieszkowska, Agnieszka, Schildkraut, Joellen M, Cheng, Jin Q, and Goode, Ellen L

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Ovarian Cancer, Cancer, Genetics, Rare Diseases, Aetiology, 2.1 Biological and endogenous factors, Animals, Disease Susceptibility, Female, Genetic Variation, Humans, Middle Aged, Ovarian Neoplasms, Polymorphism, Single Nucleotide, RNA Editing, polymorphisms, RNA editing, ovarian cancer risk, AOCS Study Group, Oncology and carcinogenesis
Abstract

RNA editing in mammals is a form of post-transcriptional modification in which adenosine is converted to inosine by the adenosine deaminases acting on RNA (ADAR) family of enzymes. Based on evidence of altered ADAR expression in epithelial ovarian cancers (EOC), we hypothesized that single nucleotide polymorphisms (SNPs) in ADAR genes modify EOC susceptibility, potentially by altering ovarian tissue gene expression. Using directly genotyped and imputed data from 10,891 invasive EOC cases and 21,693 controls, we evaluated the associations of 5,303 SNPs in ADAD1, ADAR, ADAR2, ADAR3, and SND1. Unconditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI), with adjustment for European ancestry. We conducted gene-level analyses using the Admixture Maximum Likelihood (AML) test and the Sequence-Kernel Association test for common and rare variants (SKAT-CR). Association analysis revealed top risk-associated SNP rs77027562 (OR (95% CI)= 1.39 (1.17-1.64), P=1.0x10-4) in ADAR3 and rs185455523 in SND1 (OR (95% CI)= 0.68 (0.56-0.83), P=2.0x10-4). When restricting to serous histology (n=6,500), the magnitude of association strengthened for rs185455523 (OR=0.60, P=1.0x10-4). Gene-level analyses revealed that variation in ADAR was associated (P

Published
2016

39. Association of vitamin D levels and risk of ovarian cancer: a Mendelian randomization study.

Author

Ong, Jue-Sheng, Cuellar-Partida, Gabriel, Lu, Yi, Australian Ovarian Cancer Study, Fasching, Peter A, Hein, Alexander, Burghaus, Stefanie, Beckmann, Matthias W, Lambrechts, Diether, Van Nieuwenhuysen, Els, Vergote, Ignace, Vanderstichele, Adriaan, Anne Doherty, Jennifer, Anne Rossing, Mary, Chang-Claude, Jenny, Eilber, Ursula, Rudolph, Anja, Wang-Gohrke, Shan, Goodman, Marc T, Bogdanova, Natalia, Dörk, Thilo, Dürst, Matthias, Hillemanns, Peter, Runnebaum, Ingo B, Antonenkova, Natalia, Butzow, Ralf, Leminen, Arto, Nevanlinna, Heli, Pelttari, Liisa M, Edwards, Robert P, Kelley, Joseph L, Modugno, Francesmary, Moysich, Kirsten B, Ness, Roberta B, Cannioto, Rikki, Høgdall, Estrid, Høgdall, Claus K, Jensen, Allan, Giles, Graham G, Bruinsma, Fiona, Kjaer, Susanne K, Hildebrandt, Michelle At, Liang, Dong, Lu, Karen H, Wu, Xifeng, Bisogna, Maria, Dao, Fanny, Levine, Douglas A, Cramer, Daniel W, Terry, Kathryn L, Tworoger, Shelley S, Stampfer, Meir, Missmer, Stacey, Bjorge, Line, Salvesen, Helga B, Kopperud, Reidun K, Bischof, Katharina, Aben, Katja Kh, Kiemeney, Lambertus A, Massuger, Leon Fag, Brooks-Wilson, Angela, Olson, Sara H, McGuire, Valerie, Rothstein, Joseph H, Sieh, Weiva, Whittemore, Alice S, Cook, Linda S, Le, Nhu D, Gilks, C Blake, Gronwald, Jacek, Jakubowska, Anna, Lubiński, Jan, Kluz, Tomasz, Song, Honglin, Tyrer, Jonathan P, Wentzensen, Nicolas, Brinton, Louise, Trabert, Britton, Lissowska, Jolanta, McLaughlin, John R, Narod, Steven A, Phelan, Catherine, Anton-Culver, Hoda, Ziogas, Argyrios, Eccles, Diana, Campbell, Ian, Gayther, Simon A, Gentry-Maharaj, Aleksandra, Menon, Usha, Ramus, Susan J, Wu, Anna H, Dansonka-Mieszkowska, Agnieszka, Kupryjanczyk, Jolanta, Timorek, Agnieszka, Szafron, Lukasz, Cunningham, Julie M, Fridley, Brooke L, Winham, Stacey J, Bandera, Elisa V, and Poole, Elizabeth M

Subjects
Australian Ovarian Cancer Study, Humans, Neoplasms, Glandular and Epithelial, Ovarian Neoplasms, Genetic Predisposition to Disease, Vitamin D, Odds Ratio, Risk Factors, Polymorphism, Single Nucleotide, Female, Mendelian Randomization Analysis, Carcinoma, Ovarian Epithelial, Neoplasms, Glandular and Epithelial, Polymorphism, Single Nucleotide, Carcinoma, Ovarian Epithelial, Prevention, Rare Diseases, Nutrition, Clinical Research, Cancer, Ovarian Cancer, Statistics, Public Health and Health Services, Epidemiology
Abstract

BackgroundIn vitro and observational epidemiological studies suggest that vitamin D may play a role in cancer prevention. However, the relationship between vitamin D and ovarian cancer is uncertain, with observational studies generating conflicting findings. A potential limitation of observational studies is inadequate control of confounding. To overcome this problem, we used Mendelian randomization (MR) to evaluate the association between single nucleotide polymorphisms (SNPs) associated with circulating 25-hydroxyvitamin D [25(OH)D] concentration and risk of ovarian cancer.MethodsWe employed SNPs with well-established associations with 25(OH)D concentration as instrumental variables for MR: rs7944926 (DHCR7), rs12794714 (CYP2R1) and rs2282679 (GC). We included 31 719 women of European ancestry (10 065 cases, 21 654 controls) from the Ovarian Cancer Association Consortium, who were genotyped using customized Illumina Infinium iSelect (iCOGS) arrays. A two-sample (summary data) MR approach was used and analyses were performed separately for all ovarian cancer (10 065 cases) and for high-grade serous ovarian cancer (4121 cases).ResultsThe odds ratio for epithelial ovarian cancer risk (10 065 cases) estimated by combining the individual SNP associations using inverse variance weighting was 1.27 (95% confidence interval: 1.06 to 1.51) per 20 nmol/L decrease in 25(OH)D concentration. The estimated odds ratio for high-grade serous epithelial ovarian cancer (4121 cases) was 1.54 (1.19, 2.01).ConclusionsGenetically lowered 25-hydroxyvitamin D concentrations were associated with higher ovarian cancer susceptibility in Europeans. These findings suggest that increasing plasma vitamin D levels may reduce risk of ovarian cancer.

Published
2016

41. Randomized phase 2 trial of tremelimumab and durvalumab in combination versus sequentially in recurrent platinum‐resistant ovarian cancer.

Author

Hinchcliff, Emily M., Knisely, Anne, Adjei, Naomi, Fellman, Bryan, Yuan, Ying, Patel, Ami, Xu, Cai, Westin, Shannon N., Sood, Anil K., Soliman, Pamela T., Shafer, Aaron, Fleming, Nicole D., Gershenson, David M., Vikram, Raghunandan, Bathala, Tharakeswara, Vining, David, Ganeshan, Dhakshina M., Lu, Karen H., Sun, Charlotte C., and Meyer, Larissa A.

Subjects
OVARIAN cancer, IMMUNE checkpoint inhibitors, IMMUNE checkpoint proteins, PROGRESSION-free survival, SALPINGECTOMY, CA 125 test
Abstract

Background: Single‐agent immune checkpoint inhibitors (ICIs) have demonstrated limited responses in recurrent ovarian cancer; however, 30%–40% of patients achieve stable disease. The primary objective was to estimate progression‐free survival (PFS) after sequential versus combination cytotoxic T‐lymphocyte antigen 4 and programmed death ligand 1 ICIs in patients with platinum‐resistant high‐grade serous ovarian cancer (HGSOC). Methods: Patients were randomized to a sequential arm (tremelimumab followed by durvalumab on progression) or a combination arm (tremelimumab plus durvalumab, followed by durvalumab) via a Bayesian adaptive design that made it more likely for patients to be randomized to the more effective arm. The primary end point was immune‐related PFS (irPFS). Results: Sixty‐one subjects were randomized to sequential (n = 38) or combination therapy (n = 23). Thirteen patients (34.2%) in the sequential arm received durvalumab. There was no difference in PFS in the sequential arm (1.84 months; 95% CI, 1.77–2.17 months) compared with the combination arm (1.87 months; 95% CI, 1.77–2.43 months) (p =.402). In the sequential arm, no responses were observed, although 12 patients (31.6%) demonstrated stable disease. In the combination arm, two patients (8.7%) had partial response, whereas one patient (4.4%) had stable disease. Adverse events were consistent with those previously reported for ICIs. Patient‐reported outcomes were similar in both arms. Conclusions: There was no difference in irPFS for combination tremelimumab plus durvalumab compared to tremelimumab alone (administered as part of a sequential treatment strategy) in a heavily pretreated population of patients with platinum‐resistant HGSOC. Response rates were comparable to prior reports, although the combination regimen did not add significant benefit, as has been previously described. There was no difference in the median progression‐free survival for combination tremelimumab plus durvalumab compared to tremelimumab alone (administered as part of a sequential treatment strategy) in a heavily pretreated population of patients with platinum‐resistant high‐grade serous ovarian cancer. The adverse event profile was consistent with that previously reported for immune checkpoint blockade, and patient‐reported outcomes were similar in both arms. [ABSTRACT FROM AUTHOR]

Published
2024
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42. Molecular Analysis of Clinically Defined Subsets of High-Grade Serous Ovarian Cancer

Author

Lee, Sanghoon, Zhao, Li, Rojas, Christine, Bateman, Nicholas W., Yao, Hui, Lara, Olivia D., Celestino, Joseph, Morgan, Margaret B., Nguyen, Tri V., Conrads, Kelly A., Rangel, Kelly M., Dood, Robert L., Hajek, Richard A., Fawcett, Gloria L., Chu, Randy A., Wilson, Katlin, Loffredo, Jeremy L., Viollet, Coralie, Jazaeri, Amir A., Dalgard, Clifton L., Mao, Xizeng, Song, Xingzhi, Zhou, Ming, Hood, Brian L., Banskota, Nirad, Wilkerson, Matthew D., Te, Jerez, Soltis, Anthony R., Roman, Kristin, Dunn, Andrew, Cordover, David, Eterovic, Agda Karina, Liu, Jinsong, Burks, Jared K., Baggerly, Keith A., Fleming, Nicole D., Lu, Karen H., Westin, Shannon N., Coleman, Robert L., Mills, Gordon B., Casablanca, Yovanni, Zhang, Jianhua, Conrads, Thomas P., Maxwell, George L., Futreal, P. Andrew, and Sood, Anil K.

Published
2020
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43. Assessing the genetic architecture of epithelial ovarian cancer histological subtypes

Author

Cuellar-Partida, Gabriel, Lu, Yi, Dixon, Suzanne C, Australian Ovarian Cancer Study, Fasching, Peter A, Hein, Alexander, Burghaus, Stefanie, Beckmann, Matthias W, Lambrechts, Diether, Van Nieuwenhuysen, Els, Vergote, Ignace, Vanderstichele, Adriaan, Doherty, Jennifer Anne, Rossing, Mary Anne, Chang-Claude, Jenny, Rudolph, Anja, Wang-Gohrke, Shan, Goodman, Marc T, Bogdanova, Natalia, Dörk, Thilo, Dürst, Matthias, Hillemanns, Peter, Runnebaum, Ingo B, Antonenkova, Natalia, Butzow, Ralf, Leminen, Arto, Nevanlinna, Heli, Pelttari, Liisa M, Edwards, Robert P, Kelley, Joseph L, Modugno, Francesmary, Moysich, Kirsten B, Ness, Roberta B, Cannioto, Rikki, Høgdall, Estrid, Høgdall, Claus, Jensen, Allan, Giles, Graham G, Bruinsma, Fiona, Kjaer, Susanne K, Hildebrandt, Michelle AT, Liang, Dong, Lu, Karen H, Wu, Xifeng, Bisogna, Maria, Dao, Fanny, Levine, Douglas A, Cramer, Daniel W, Terry, Kathryn L, Tworoger, Shelley S, Stampfer, Meir, Missmer, Stacey, Bjorge, Line, Salvesen, Helga B, Kopperud, Reidun K, Bischof, Katharina, Aben, Katja KH, Kiemeney, Lambertus A, Massuger, Leon FAG, Brooks-Wilson, Angela, Olson, Sara H, McGuire, Valerie, Rothstein, Joseph H, Sieh, Weiva, Whittemore, Alice S, Cook, Linda S, Le, Nhu D, Blake Gilks, C, Gronwald, Jacek, Jakubowska, Anna, Lubiński, Jan, Kluz, Tomasz, Song, Honglin, Tyrer, Jonathan P, Wentzensen, Nicolas, Brinton, Louise, Trabert, Britton, Lissowska, Jolanta, McLaughlin, John R, Narod, Steven A, Phelan, Catherine, Anton-Culver, Hoda, Ziogas, Argyrios, Eccles, Diana, Campbell, Ian, Gayther, Simon A, Gentry-Maharaj, Aleksandra, Menon, Usha, Ramus, Susan J, Wu, Anna H, Dansonka-Mieszkowska, Agnieszka, Kupryjanczyk, Jolanta, Timorek, Agnieszka, Szafron, Lukasz, Cunningham, Julie M, Fridley, Brooke L, Winham, Stacey J, Bandera, Elisa V, Poole, Elizabeth M, and Morgan, Terry K

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Genetics, Obesity, Women's Health, Cancer Genomics, Ovarian Cancer, Cancer, Human Genome, Rare Diseases, 2.1 Biological and endogenous factors, Aetiology, Carcinoma, Ovarian Epithelial, Female, Genotype, Humans, Neoplasms, Glandular and Epithelial, Ovarian Neoplasms, Pathology, Molecular, Polymorphism, Single Nucleotide, Australian Ovarian Cancer Study, Complementary and Alternative Medicine, Paediatrics and Reproductive Medicine, Genetics & Heredity, Reproductive medicine
Abstract

Epithelial ovarian cancer (EOC) is one of the deadliest common cancers. The five most common types of disease are high-grade and low-grade serous, endometrioid, mucinous and clear cell carcinoma. Each of these subtypes present distinct molecular pathogeneses and sensitivities to treatments. Recent studies show that certain genetic variants confer susceptibility to all subtypes while other variants are subtype-specific. Here, we perform an extensive analysis of the genetic architecture of EOC subtypes. To this end, we used data of 10,014 invasive EOC patients and 21,233 controls from the Ovarian Cancer Association Consortium genotyped in the iCOGS array (211,155 SNPs). We estimate the array heritability (attributable to variants tagged on arrays) of each subtype and their genetic correlations. We also look for genetic overlaps with factors such as obesity, smoking behaviors, diabetes, age at menarche and height. We estimated the array heritabilities of high-grade serous disease ([Formula: see text] = 8.8 ± 1.1 %), endometrioid ([Formula: see text] = 3.2 ± 1.6 %), clear cell ([Formula: see text] = 6.7 ± 3.3 %) and all EOC ([Formula: see text] = 5.6 ± 0.6 %). Known associated loci contributed approximately 40 % of the total array heritability for each subtype. The contribution of each chromosome to the total heritability was not proportional to chromosome size. Through bivariate and cross-trait LD score regression, we found evidence of shared genetic backgrounds between the three high-grade subtypes: serous, endometrioid and undifferentiated. Finally, we found significant genetic correlations of all EOC with diabetes and obesity using a polygenic prediction approach.

Published
2016

44. Experiences of Family Communication and Cascade Genetic Testing for Hereditary Cancer in Medically Underserved Populations — A Qualitative Study

Author

Bednar, Erica M., primary, Rauh-Hain, J. Alejandro, additional, Garcia, Jose J., additional, de Aguinaga, Norma, additional, Powell, Mary Anne, additional, Peral, Sylvia L., additional, Nitecki, Roni, additional, Jorgensen, Kirsten, additional, Rudy, Natasha L., additional, Lu, Karen H., additional, Leath, Charles A., additional, and Scarinci, Isabel C., additional

Published
2023
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45. Randomized phase 2 trial of tremelimumab and durvalumab in combination versus sequentially in recurrent platinum‐resistant ovarian cancer

Author

Hinchcliff, Emily M., primary, Knisely, Anne, additional, Adjei, Naomi, additional, Fellman, Bryan, additional, Yuan, Ying, additional, Patel, Ami, additional, Xu, Cai, additional, Westin, Shannon N., additional, Sood, Anil K., additional, Soliman, Pamela T., additional, Shafer, Aaron, additional, Fleming, Nicole D., additional, Gershenson, David M., additional, Vikram, Raghunandan, additional, Bathala, Tharakeswara, additional, Vining, David, additional, Ganeshan, Dhakshina M., additional, Lu, Karen H., additional, Sun, Charlotte C., additional, Meyer, Larissa A., additional, and Jazaeri, Amir A., additional

Published
2023
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46. Transforming ovarian cancer care by targeting minimal residual disease

Author

Jazaeri, Amir A., primary, Grisham, Rachel, additional, Knisely, Anne, additional, Spranger, Stefani, additional, Zamarin, Dmitriy, additional, Hillman, R. Tyler, additional, Lawson, Barrett C., additional, Burns, Kathleen H., additional, Lee, Sanghoon, additional, Westin, Shannon N., additional, Moiso, Enrico, additional, Williams, Marc J., additional, Bardhan, Neelkanth M., additional, Pisanic, Thomas, additional, Matulonis, Ursula, additional, Weigelt, Britta, additional, Shih, IeMing, additional, Konstantinopoulos, Panagiotis A., additional, Gaillard, Stephanie, additional, Wang, Linghua, additional, Aghajanian, Carol, additional, D’Andrea, Alan D., additional, Hammond, Paula, additional, Shah, Sohrab, additional, Wucherpfennig, Kai W., additional, and Lu, Karen H., additional

Published
2023
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47. Remotely Delivered Cancer Genetic Testing in the Making Genetic Testing Accessible (MAGENTA) Trial

Author

Swisher, Elizabeth M., primary, Rayes, Nadine, additional, Bowen, Deborah, additional, Peterson, Christine B., additional, Norquist, Barbara M., additional, Coffin, Tara, additional, Gavin, Kathleen, additional, Polinsky, Deborah, additional, Crase, Jamie, additional, Bakkum-Gamez, Jamie N., additional, Blank, Stephanie V., additional, Munsell, Mark F., additional, Nebgen, Denise, additional, Fleming, Gini F., additional, Olopade, Olufunmilayo I., additional, Law, Sherman, additional, Zhou, Alicia, additional, Levine, Douglas A., additional, D’Andrea, Alan, additional, and Lu, Karen H., additional

Published
2023
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49. Correction: Polygenic risk modeling for prediction of epithelial ovarian cancer risk

Author

Dareng, Eileen O., Tyrer, Jonathan P., Barnes, Daniel R., Jones, Michelle R., Yang, Xin, Aben, Katja K. H., Adank, Muriel A., Agata, Simona, Andrulis, Irene L., Anton-Culver, Hoda, Antonenkova, Natalia N., Aravantinos, Gerasimos, Arun, Banu K., Augustinsson, Annelie, Balmaña, Judith, Bandera, Elisa V., Barkardottir, Rosa B., Barrowdale, Daniel, Beckmann, Matthias W., Beeghly-Fadiel, Alicia, Benitez, Javier, Bermisheva, Marina, Bernardini, Marcus Q., Bjorge, Line, Black, Amanda, Bogdanova, Natalia V., Bonanni, Bernardo, Borg, Ake, Brenton, James D., Budzilowska, Agnieszka, Butzow, Ralf, Buys, Saundra S., Cai, Hui, Caligo, Maria A., Campbell, Ian, Cannioto, Rikki, Cassingham, Hayley, Chang-Claude, Jenny, Chanock, Stephen J., Chen, Kexin, Chiew, Yoke-Eng, Chung, Wendy K., Claes, Kathleen B. M., Colonna, Sarah, Cook, Linda S., Couch, Fergus J., Daly, Mary B., Dao, Fanny, Davies, Eleanor, de la Hoya, Miguel, de Putter, Robin, Dennis, Joe, DePersia, Allison, Devilee, Peter, Diez, Orland, Ding, Yuan Chun, Doherty, Jennifer A., Domchek, Susan M., Dörk, Thilo, du Bois, Andreas, Dürst, Matthias, Eccles, Diana M., Eliassen, Heather A., Engel, Christoph, Evans, Gareth D., Fasching, Peter A., Flanagan, James M., Fortner, Renée T., Machackova, Eva, Friedman, Eitan, Ganz, Patricia A., Garber, Judy, Gensini, Francesca, Giles, Graham G., Glendon, Gord, Godwin, Andrew K., Goodman, Marc T., Greene, Mark H., Gronwald, Jacek, Hahnen, Eric, Haiman, Christopher A., Håkansson, Niclas, Hamann, Ute, Hansen, Thomas V. O., Harris, Holly R., Hartman, Mikael, Heitz, Florian, Hildebrandt, Michelle A. T., Høgdall, Estrid, Høgdall, Claus K., Hopper, John L., Huang, Ruea-Yea, Huff, Chad, Hulick, Peter J., Huntsman, David G., Imyanitov, Evgeny N., Isaacs, Claudine, Jakubowska, Anna, James, Paul A., Janavicius, Ramunas, Jensen, Allan, Johannsson, Oskar Th., John, Esther M., Jones, Michael E., Kang, Daehee, Karlan, Beth Y., Karnezis, Anthony, Kelemen, Linda E., Khusnutdinova, Elza, Kiemeney, Lambertus A., Kim, Byoung-Gie, Kjaer, Susanne K., Komenaka, Ian, Kupryjanczyk, Jolanta, Kurian, Allison W., Kwong, Ava, Lambrechts, Diether, Larson, Melissa C., Lazaro, Conxi, Le, Nhu D., Leslie, Goska, Lester, Jenny, Lesueur, Fabienne, Levine, Douglas A., Li, Lian, Li, Jingmei, Loud, Jennifer T., Lu, Karen H., Lubiński, Jan, Mai, Phuong L., Manoukian, Siranoush, Marks, Jeffrey R., Matsuno, Rayna Kim, Matsuo, Keitaro, May, Taymaa, McGuffog, Lesley, McLaughlin, John R., McNeish, Iain A., Mebirouk, Noura, Menon, Usha, Miller, Austin, Milne, Roger L., Minlikeeva, Albina, Modugno, Francesmary, Montagna, Marco, Moysich, Kirsten B., Munro, Elizabeth, Nathanson, Katherine L., Neuhausen, Susan L., Nevanlinna, Heli, Yie, Joanne Ngeow Yuen, Nielsen, Henriette Roed, Nielsen, Finn C., Nikitina-Zake, Liene, Odunsi, Kunle, Offit, Kenneth, Olah, Edith, Olbrecht, Siel, Olopade, Olufunmilayo I., Olson, Sara H., Olsson, Håkan, Osorio, Ana, Papi, Laura, Park, Sue K., Parsons, Michael T., Pathak, Harsha, Pedersen, Inge Sokilde, Peixoto, Ana, Pejovic, Tanja, Perez-Segura, Pedro, Permuth, Jennifer B., Peshkin, Beth, Peterlongo, Paolo, Piskorz, Anna, Prokofyeva, Darya, Radice, Paolo, Rantala, Johanna, Riggan, Marjorie J., Risch, Harvey A., Rodriguez-Antona, Cristina, Ross, Eric, Rossing, Mary Anne, Runnebaum, Ingo, Sandler, Dale P., Santamariña, Marta, Soucy, Penny, Schmutzler, Rita K., Setiawan, V. Wendy, Shan, Kang, Sieh, Weiva, Simard, Jacques, Singer, Christian F., Sokolenko, Anna P., Song, Honglin, Southey, Melissa C., Steed, Helen, Stoppa-Lyonnet, Dominique, Sutphen, Rebecca, Swerdlow, Anthony J., Tan, Yen Yen, Teixeira, Manuel R., Teo, Soo Hwang, Terry, Kathryn L., Terry, Mary Beth, Thomassen, Mads, Thompson, Pamela J., Thomsen, Liv Cecilie Vestrheim, Thull, Darcy L., Tischkowitz, Marc, Titus, Linda, Toland, Amanda E., Torres, Diana, Trabert, Britton, Travis, Ruth, Tung, Nadine, Tworoger, Shelley S., Valen, Ellen, van Altena, Anne M., van der Hout, Annemieke H., Van Nieuwenhuysen, Els, van Rensburg, Elizabeth J., Vega, Ana, Edwards, Digna Velez, Vierkant, Robert A., Wang, Frances, Wappenschmidt, Barbara, Webb, Penelope M., Weinberg, Clarice R., Weitzel, Jeffrey N., Wentzensen, Nicolas, White, Emily, Whittemore, Alice S., Winham, Stacey J., Wolk, Alicja, Woo, Yin-Ling, Wu, Anna H., Yan, Li, Yannoukakos, Drakoulis, Zavaglia, Katia M., Zheng, Wei, Ziogas, Argyrios, Zorn, Kristin K., Kleibl, Zdenek, Easton, Douglas, Lawrenson, Kate, DeFazio, Anna, Sellers, Thomas A., Ramus, Susan J., Pearce, Celeste L., Monteiro, Alvaro N., Cunningham, Julie, Goode, Ellen L., Schildkraut, Joellen M., Berchuck, Andrew, Chenevix-Trench, Georgia, Gayther, Simon A., Antoniou, Antonis C., and Pharoah, Paul D. P.

Published
2022
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50. Rethinking ovarian cancer II: reducing mortality from high-grade serous ovarian cancer

Author

Bowtell, David D, Böhm, Steffen, Ahmed, Ahmed A, Aspuria, Paul-Joseph, Bast, Robert C, Beral, Valerie, Berek, Jonathan S, Birrer, Michael J, Blagden, Sarah, Bookman, Michael A, Brenton, James D, Chiappinelli, Katherine B, Martins, Filipe Correia, Coukos, George, Drapkin, Ronny, Edmondson, Richard, Fotopoulou, Christina, Gabra, Hani, Galon, Jérôme, Gourley, Charlie, Heong, Valerie, Huntsman, David G, Iwanicki, Marcin, Karlan, Beth Y, Kaye, Allyson, Lengyel, Ernst, Levine, Douglas A, Lu, Karen H, McNeish, Iain A, Menon, Usha, Narod, Steven A, Nelson, Brad H, Nephew, Kenneth P, Pharoah, Paul, Powell, Daniel J, Ramos, Pilar, Romero, Iris L, Scott, Clare L, Sood, Anil K, Stronach, Euan A, and Balkwill, Frances R

Subjects
Cancer, Ovarian Cancer, Prevention, Rare Diseases, Good Health and Well Being, Cystadenocarcinoma, Serous, Female, Humans, Neoplasm Grading, Ovarian Neoplasms, Prognosis, Survival Rate, Medical and Health Sciences, Oncology & Carcinogenesis
Abstract

High-grade serous ovarian cancer (HGSOC) accounts for 70-80% of ovarian cancer deaths, and overall survival has not changed significantly for several decades. In this Opinion article, we outline a set of research priorities that we believe will reduce incidence and improve outcomes for women with this disease. This 'roadmap' for HGSOC was determined after extensive discussions at an Ovarian Cancer Action meeting in January 2015.

Published
2015

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