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151. CCNE1 and survival of patients with tubo‐ovarian high‐grade serous carcinoma: An Ovarian Tumor Tissue Analysis consortium study

Author: Kang, Eun‐Young, Kang, Eun‐Young, Weir, Ashley, Meagher, Nicola S, Farrington, Kyo, Nelson, Gregg S, Ghatage, Prafull, Lee, Cheng‐Han, Riggan, Marjorie J, Bolithon, Adelyn, Popovic, Gordana, Leung, Betty, Tang, Katrina, Lambie, Neil, Millstein, Joshua, Alsop, Jennifer, Anglesio, Michael S, Ataseven, Beyhan, Barlow, Ellen, Beckmann, Matthias W, Berger, Jessica, Bisinotto, Christiani, Bösmüller, Hans, Boros, Jessica, Brand, Alison H, Brooks‐Wilson, Angela, Brucker, Sara Y, Carney, Michael E, Casablanca, Yovanni, Cazorla‐Jiménez, Alicia, Cohen, Paul A, Conrads, Thomas P, Cook, Linda S, Coulson, Penny, Courtney‐Brooks, Madeleine, Cramer, Daniel W, Crowe, Philip, Cunningham, Julie M, Cybulski, Cezary, Darcy, Kathleen M, El‐Bahrawy, Mona A, Elishaev, Esther, Erber, Ramona, Farrell, Rhonda, Fereday, Sian, Fischer, Anna, García, María J, Gayther, Simon A, Gentry‐Maharaj, Aleksandra, Gilks, C Blake, Group, AOCS, Grube, Marcel, Harnett, Paul R, Harrington, Shariska Petersen, Harter, Philipp, Hartmann, Arndt, Hecht, Jonathan L, Heikaus, Sebastian, Hein, Alexander, Heitz, Florian, Hendley, Joy, Hernandez, Brenda Y, Polo, Susanna Hernando, Heublein, Sabine, Hirasawa, Akira, Høgdall, Estrid, Høgdall, Claus K, Horlings, Hugo M, Huntsman, David G, Huzarski, Tomasz, Jewell, Andrea, Jimenez‐Linan, Mercedes, Jones, Michael E, Kaufmann, Scott H, Kennedy, Catherine J, Khabele, Dineo, Kommoss, Felix KF, Kruitwagen, Roy FPM, Lambrechts, Diether, Le, Nhu D, Lener, Marcin, Lester, Jenny, Leung, Yee, Linder, Anna, Loverix, Liselore, Lubiński, Jan, Madan, Rashna, Maxwell, G Larry, Modugno, Francesmary, Neuhausen, Susan L, Olawaiye, Alexander, Olbrecht, Siel, Orsulic, Sandra, Palacios, José, Pearce, Celeste Leigh, Pike, Malcolm C, Quinn, Carmel M, Mohan, Ganendra Raj, Rodríguez‐Antona, Cristina, Ruebner, Matthias, Ryan, Andy, Kang, Eun‐Young, Kang, Eun‐Young, Weir, Ashley, Meagher, Nicola S, Farrington, Kyo, Nelson, Gregg S, Ghatage, Prafull, Lee, Cheng‐Han, Riggan, Marjorie J, Bolithon, Adelyn, Popovic, Gordana, Leung, Betty, Tang, Katrina, Lambie, Neil, Millstein, Joshua, Alsop, Jennifer, Anglesio, Michael S, Ataseven, Beyhan, Barlow, Ellen, Beckmann, Matthias W, Berger, Jessica, Bisinotto, Christiani, Bösmüller, Hans, Boros, Jessica, Brand, Alison H, Brooks‐Wilson, Angela, Brucker, Sara Y, Carney, Michael E, Casablanca, Yovanni, Cazorla‐Jiménez, Alicia, Cohen, Paul A, Conrads, Thomas P, Cook, Linda S, Coulson, Penny, Courtney‐Brooks, Madeleine, Cramer, Daniel W, Crowe, Philip, Cunningham, Julie M, Cybulski, Cezary, Darcy, Kathleen M, El‐Bahrawy, Mona A, Elishaev, Esther, Erber, Ramona, Farrell, Rhonda, Fereday, Sian, Fischer, Anna, García, María J, Gayther, Simon A, Gentry‐Maharaj, Aleksandra, Gilks, C Blake, Group, AOCS, Grube, Marcel, Harnett, Paul R, Harrington, Shariska Petersen, Harter, Philipp, Hartmann, Arndt, Hecht, Jonathan L, Heikaus, Sebastian, Hein, Alexander, Heitz, Florian, Hendley, Joy, Hernandez, Brenda Y, Polo, Susanna Hernando, Heublein, Sabine, Hirasawa, Akira, Høgdall, Estrid, Høgdall, Claus K, Horlings, Hugo M, Huntsman, David G, Huzarski, Tomasz, Jewell, Andrea, Jimenez‐Linan, Mercedes, Jones, Michael E, Kaufmann, Scott H, Kennedy, Catherine J, Khabele, Dineo, Kommoss, Felix KF, Kruitwagen, Roy FPM, Lambrechts, Diether, Le, Nhu D, Lener, Marcin, Lester, Jenny, Leung, Yee, Linder, Anna, Loverix, Liselore, Lubiński, Jan, Madan, Rashna, Maxwell, G Larry, Modugno, Francesmary, Neuhausen, Susan L, Olawaiye, Alexander, Olbrecht, Siel, Orsulic, Sandra, Palacios, José, Pearce, Celeste Leigh, Pike, Malcolm C, Quinn, Carmel M, Mohan, Ganendra Raj, Rodríguez‐Antona, Cristina, Ruebner, Matthias, and Ryan, Andy
Abstract: BackgroundCyclin E1 (CCNE1) is a potential predictive marker and therapeutic target in tubo-ovarian high-grade serous carcinoma (HGSC). Smaller studies have revealed unfavorable associations for CCNE1 amplification and CCNE1 overexpression with survival, but to date no large-scale, histotype-specific validation has been performed. The hypothesis was that high-level amplification of CCNE1 and CCNE1 overexpression, as well as a combination of the two, are linked to shorter overall survival in HGSC.MethodsWithin the Ovarian Tumor Tissue Analysis consortium, amplification status and protein level in 3029 HGSC cases and mRNA expression in 2419 samples were investigated.ResultsHigh-level amplification (>8 copies by chromogenic in situ hybridization) was found in 8.6% of HGSC and overexpression (>60% with at least 5% demonstrating strong intensity by immunohistochemistry) was found in 22.4%. CCNE1 high-level amplification and overexpression both were linked to shorter overall survival in multivariate survival analysis adjusted for age and stage, with hazard stratification by study (hazard ratio [HR], 1.26; 95% CI, 1.08-1.47, p = .034, and HR, 1.18; 95% CI, 1.05-1.32, p = .015, respectively). This was also true for cases with combined high-level amplification/overexpression (HR, 1.26; 95% CI, 1.09-1.47, p = .033). CCNE1 mRNA expression was not associated with overall survival (HR, 1.00 per 1-SD increase; 95% CI, 0.94-1.06; p = .58). CCNE1 high-level amplification is mutually exclusive with the presence of germline BRCA1/2 pathogenic variants and shows an inverse association to RB1 loss.ConclusionThis study provides large-scale validation that CCNE1 high-level amplification is associated with shorter survival, supporting its utility as a prognostic biomarker in HGSC.
Published: 2023

152. p53 and ovarian carcinoma survival: an Ovarian Tumor Tissue Analysis consortium study

Author: Köbel, Martin, Köbel, Martin, Kang, Eun‐Young, Weir, Ashley, Rambau, Peter F, Lee, Cheng‐Han, Nelson, Gregg S, Ghatage, Prafull, Meagher, Nicola S, Riggan, Marjorie J, Alsop, Jennifer, Anglesio, Michael S, Beckmann, Matthias W, Bisinotto, Christiani, Boisen, Michelle, Boros, Jessica, Brand, Alison H, Brooks‐Wilson, Angela, Carney, Michael E, Coulson, Penny, Courtney‐Brooks, Madeleine, Cushing‐Haugen, Kara L, Cybulski, Cezary, Deen, Suha, El‐Bahrawy, Mona A, Elishaev, Esther, Erber, Ramona, Fereday, Sian, Group, AOCS, Fischer, Anna, Gayther, Simon A, Barquin‐Garcia, Arantzazu, Gentry‐Maharaj, Aleksandra, Gilks, C Blake, Gronwald, Helena, Grube, Marcel, Harnett, Paul R, Harris, Holly R, Hartkopf, Andreas D, Hartmann, Arndt, Hein, Alexander, Hendley, Joy, Hernandez, Brenda Y, Huang, Yajue, Jakubowska, Anna, Jimenez‐Linan, Mercedes, Jones, Michael E, Kennedy, Catherine J, Kluz, Tomasz, Koziak, Jennifer M, Lesnock, Jaime, Lester, Jenny, Lubiński, Jan, Longacre, Teri A, Lycke, Maria, Mateoiu, Constantina, McCauley, Bryan M, McGuire, Valerie, Ney, Britta, Olawaiye, Alexander, Orsulic, Sandra, Osorio, Ana, Paz‐Ares, Luis, Ramón y Cajal, Teresa, Rothstein, Joseph H, Ruebner, Matthias, Schoemaker, Minouk J, Shah, Mitul, Sharma, Raghwa, Sherman, Mark E, Shvetsov, Yurii B, Singh, Naveena, Steed, Helen, Storr, Sarah J, Talhouk, Aline, Traficante, Nadia, Wang, Chen, Whittemore, Alice S, Widschwendter, Martin, Wilkens, Lynne R, Winham, Stacey J, Benitez, Javier, Berchuck, Andrew, Bowtell, David D, dos Reis, Francisco J Candido, Campbell, Ian, Cook, Linda S, DeFazio, Anna, Doherty, Jennifer A, Fasching, Peter A, Fortner, Renée T, García, María J, Goodman, Marc T, Goode, Ellen L, Gronwald, Jacek, Huntsman, David G, Karlan, Beth Y, Kelemen, Linda E, Kommoss, Stefan, Le, Nhu D, Martin, Stewart G, Köbel, Martin, Köbel, Martin, Kang, Eun‐Young, Weir, Ashley, Rambau, Peter F, Lee, Cheng‐Han, Nelson, Gregg S, Ghatage, Prafull, Meagher, Nicola S, Riggan, Marjorie J, Alsop, Jennifer, Anglesio, Michael S, Beckmann, Matthias W, Bisinotto, Christiani, Boisen, Michelle, Boros, Jessica, Brand, Alison H, Brooks‐Wilson, Angela, Carney, Michael E, Coulson, Penny, Courtney‐Brooks, Madeleine, Cushing‐Haugen, Kara L, Cybulski, Cezary, Deen, Suha, El‐Bahrawy, Mona A, Elishaev, Esther, Erber, Ramona, Fereday, Sian, Group, AOCS, Fischer, Anna, Gayther, Simon A, Barquin‐Garcia, Arantzazu, Gentry‐Maharaj, Aleksandra, Gilks, C Blake, Gronwald, Helena, Grube, Marcel, Harnett, Paul R, Harris, Holly R, Hartkopf, Andreas D, Hartmann, Arndt, Hein, Alexander, Hendley, Joy, Hernandez, Brenda Y, Huang, Yajue, Jakubowska, Anna, Jimenez‐Linan, Mercedes, Jones, Michael E, Kennedy, Catherine J, Kluz, Tomasz, Koziak, Jennifer M, Lesnock, Jaime, Lester, Jenny, Lubiński, Jan, Longacre, Teri A, Lycke, Maria, Mateoiu, Constantina, McCauley, Bryan M, McGuire, Valerie, Ney, Britta, Olawaiye, Alexander, Orsulic, Sandra, Osorio, Ana, Paz‐Ares, Luis, Ramón y Cajal, Teresa, Rothstein, Joseph H, Ruebner, Matthias, Schoemaker, Minouk J, Shah, Mitul, Sharma, Raghwa, Sherman, Mark E, Shvetsov, Yurii B, Singh, Naveena, Steed, Helen, Storr, Sarah J, Talhouk, Aline, Traficante, Nadia, Wang, Chen, Whittemore, Alice S, Widschwendter, Martin, Wilkens, Lynne R, Winham, Stacey J, Benitez, Javier, Berchuck, Andrew, Bowtell, David D, dos Reis, Francisco J Candido, Campbell, Ian, Cook, Linda S, DeFazio, Anna, Doherty, Jennifer A, Fasching, Peter A, Fortner, Renée T, García, María J, Goodman, Marc T, Goode, Ellen L, Gronwald, Jacek, Huntsman, David G, Karlan, Beth Y, Kelemen, Linda E, Kommoss, Stefan, Le, Nhu D, and Martin, Stewart G
Abstract: Our objective was to test whether p53 expression status is associated with survival for women diagnosed with the most common ovarian carcinoma histotypes (high-grade serous carcinoma [HGSC], endometrioid carcinoma [EC], and clear cell carcinoma [CCC]) using a large multi-institutional cohort from the Ovarian Tumor Tissue Analysis (OTTA) consortium. p53 expression was assessed on 6,678 cases represented on tissue microarrays from 25 participating OTTA study sites using a previously validated immunohistochemical (IHC) assay as a surrogate for the presence and functional effect of TP53 mutations. Three abnormal expression patterns (overexpression, complete absence, and cytoplasmic) and the normal (wild type) pattern were recorded. Survival analyses were performed by histotype. The frequency of abnormal p53 expression was 93.4% (4,630/4,957) in HGSC compared to 11.9% (116/973) in EC and 11.5% (86/748) in CCC. In HGSC, there were no differences in overall survival across the abnormal p53 expression patterns. However, in EC and CCC, abnormal p53 expression was associated with an increased risk of death for women diagnosed with EC in multivariate analysis compared to normal p53 as the reference (hazard ratio [HR] = 2.18, 95% confidence interval [CI] 1.36-3.47, p = 0.0011) and with CCC (HR = 1.57, 95% CI 1.11-2.22, p = 0.012). Abnormal p53 was also associated with shorter overall survival in The International Federation of Gynecology and Obstetrics stage I/II EC and CCC. Our study provides further evidence that functional groups of TP53 mutations assessed by abnormal surrogate p53 IHC patterns are not associated with survival in HGSC. In contrast, we validate that abnormal p53 IHC is a strong independent prognostic marker for EC and demonstrate for the first time an independent prognostic association of abnormal p53 IHC with overall survival in patients with CCC.
Published: 2023

153. Profiling the immune landscape in mucinous ovarian carcinoma.

Author: Meagher, Nicola, Meagher, Nicola, Hamilton, Phineas, Milne, Katy, Thornton, Shelby, Harris, Bronwyn, Weir, Ashley, Alsop, Jennifer, Bisinoto, Christiani, Brenton, James, Brooks-Wilson, Angela, Chiu, Derek, Cushing-Haugen, Kara, Fereday, Sian, Garsed, Dale, Gayther, Simon, Gentry-Maharaj, Aleksandra, Gilks, Blake, Jimenez-Linan, Mercedes, Kennedy, Catherine, Le, Nhu, Piskorz, Anna, Riggan, Marjorie, Shah, Mitul, Singh, Naveena, Talhouk, Aline, Widschwendter, Martin, Bowtell, David, Candido Dos Reis, Francisco, Cook, Linda, Fortner, Renée, García, María, Harris, Holly, Huntsman, David, Köbel, Martin, Menon, Usha, Pharoah, Paul, Doherty, Jennifer, Anglesio, Michael, Pike, Malcolm, Pearce, Celeste, Friedlander, Michael, DeFazio, Anna, Nelson, Brad, Ramus, Susan, Karnezis, Anthony, Meagher, Nicola, Meagher, Nicola, Hamilton, Phineas, Milne, Katy, Thornton, Shelby, Harris, Bronwyn, Weir, Ashley, Alsop, Jennifer, Bisinoto, Christiani, Brenton, James, Brooks-Wilson, Angela, Chiu, Derek, Cushing-Haugen, Kara, Fereday, Sian, Garsed, Dale, Gayther, Simon, Gentry-Maharaj, Aleksandra, Gilks, Blake, Jimenez-Linan, Mercedes, Kennedy, Catherine, Le, Nhu, Piskorz, Anna, Riggan, Marjorie, Shah, Mitul, Singh, Naveena, Talhouk, Aline, Widschwendter, Martin, Bowtell, David, Candido Dos Reis, Francisco, Cook, Linda, Fortner, Renée, García, María, Harris, Holly, Huntsman, David, Köbel, Martin, Menon, Usha, Pharoah, Paul, Doherty, Jennifer, Anglesio, Michael, Pike, Malcolm, Pearce, Celeste, Friedlander, Michael, DeFazio, Anna, Nelson, Brad, Ramus, Susan, and Karnezis, Anthony
Abstract: OBJECTIVE: Mucinous ovarian carcinoma (MOC) is a rare histotype of ovarian cancer, with low response rates to standard chemotherapy, and very poor survival for patients diagnosed at advanced stage. There is a limited understanding of the MOC immune landscape, and consequently whether immune checkpoint inhibitors could be considered for a subset of patients. METHODS: We performed multicolor immunohistochemistry (IHC) and immunofluorescence (IF) on tissue microarrays in a cohort of 126 MOC patients. Cell densities were calculated in the epithelial and stromal components for tumor-associated macrophages (CD68+/PD-L1+, CD68+/PD-L1-), T cells (CD3+/CD8-, CD3+/CD8+), putative T-regulatory cells (Tregs, FOXP3+), B cells (CD20+/CD79A+), plasma cells (CD20-/CD79a+), and PD-L1+ and PD-1+ cells, and compared these values with clinical factors. Univariate and multivariable Cox Proportional Hazards assessed overall survival. Unsupervised k-means clustering identified patient subsets with common patterns of immune cell infiltration. RESULTS: Mean densities of PD1+ cells, PD-L1- macrophages, CD4+ and CD8+ T cells, and FOXP3+ Tregs were higher in the stroma compared to the epithelium. Tumors from advanced (Stage III/IV) MOC had greater epithelial infiltration of PD-L1- macrophages, and fewer PD-L1+ macrophages compared with Stage I/II cancers (p = 0.004 and p = 0.014 respectively). Patients with high epithelial density of FOXP3+ cells, CD8+/FOXP3+ cells, or PD-L1- macrophages, had poorer survival, and high epithelial CD79a + plasma cells conferred better survival, all upon univariate analysis only. Clustering showed that most MOC (86%) had an immune depleted (cold) phenotype, with only a small proportion (11/76,14%) considered immune inflamed (hot) based on T cell and PD-L1 infiltrates. CONCLUSION: In summary, MOCs are mostly immunogenically cold, suggesting they may have limited response to current immunotherapies.
Published: 2023

154. Aggregation tests identify new gene associations with breast cancer in populations with diverse ancestry.

Author: Mueller, Stefanie H, Mueller, Stefanie H, Lai, Alvina G, Valkovskaya, Maria, Michailidou, Kyriaki, Bolla, Manjeet K, Wang, Qin, Dennis, Joe, Lush, Michael, Abu-Ful, Zomoruda, Ahearn, Thomas U, Andrulis, Irene L, Anton-Culver, Hoda, Antonenkova, Natalia N, Arndt, Volker, Aronson, Kristan J, Augustinsson, Annelie, Baert, Thais, Freeman, Laura E Beane, Beckmann, Matthias W, Behrens, Sabine, Benitez, Javier, Bermisheva, Marina, Blomqvist, Carl, Bogdanova, Natalia V, Bojesen, Stig E, Bonanni, Bernardo, Brenner, Hermann, Brucker, Sara Y, Buys, Saundra S, Castelao, Jose E, Chan, Tsun L, Chang-Claude, Jenny, Chanock, Stephen J, Choi, Ji-Yeob, Chung, Wendy K, NBCS Collaborators, Colonna, Sarah V, CTS Consortium, Cornelissen, Sten, Couch, Fergus J, Czene, Kamila, Daly, Mary B, Devilee, Peter, Dörk, Thilo, Dossus, Laure, Dwek, Miriam, Eccles, Diana M, Ekici, Arif B, Eliassen, A Heather, Engel, Christoph, Evans, D Gareth, Fasching, Peter A, Fletcher, Olivia, Flyger, Henrik, Gago-Dominguez, Manuela, Gao, Yu-Tang, García-Closas, Montserrat, García-Sáenz, José A, Genkinger, Jeanine, Gentry-Maharaj, Aleksandra, Grassmann, Felix, Guénel, Pascal, Gündert, Melanie, Haeberle, Lothar, Hahnen, Eric, Haiman, Christopher A, Håkansson, Niclas, Hall, Per, Harkness, Elaine F, Harrington, Patricia A, Hartikainen, Jaana M, Hartman, Mikael, Hein, Alexander, Ho, Weang-Kee, Hooning, Maartje J, Hoppe, Reiner, Hopper, John L, Houlston, Richard S, Howell, Anthony, Hunter, David J, Huo, Dezheng, ABCTB Investigators, Ito, Hidemi, Iwasaki, Motoki, Jakubowska, Anna, Janni, Wolfgang, John, Esther M, Jones, Michael E, Jung, Audrey, Kaaks, Rudolf, Kang, Daehee, Khusnutdinova, Elza K, Kim, Sung-Won, Kitahara, Cari M, Koutros, Stella, Kraft, Peter, Kristensen, Vessela N, Kubelka-Sabit, Katerina, Kurian, Allison W, Kwong, Ava, Mueller, Stefanie H, Mueller, Stefanie H, Lai, Alvina G, Valkovskaya, Maria, Michailidou, Kyriaki, Bolla, Manjeet K, Wang, Qin, Dennis, Joe, Lush, Michael, Abu-Ful, Zomoruda, Ahearn, Thomas U, Andrulis, Irene L, Anton-Culver, Hoda, Antonenkova, Natalia N, Arndt, Volker, Aronson, Kristan J, Augustinsson, Annelie, Baert, Thais, Freeman, Laura E Beane, Beckmann, Matthias W, Behrens, Sabine, Benitez, Javier, Bermisheva, Marina, Blomqvist, Carl, Bogdanova, Natalia V, Bojesen, Stig E, Bonanni, Bernardo, Brenner, Hermann, Brucker, Sara Y, Buys, Saundra S, Castelao, Jose E, Chan, Tsun L, Chang-Claude, Jenny, Chanock, Stephen J, Choi, Ji-Yeob, Chung, Wendy K, NBCS Collaborators, Colonna, Sarah V, CTS Consortium, Cornelissen, Sten, Couch, Fergus J, Czene, Kamila, Daly, Mary B, Devilee, Peter, Dörk, Thilo, Dossus, Laure, Dwek, Miriam, Eccles, Diana M, Ekici, Arif B, Eliassen, A Heather, Engel, Christoph, Evans, D Gareth, Fasching, Peter A, Fletcher, Olivia, Flyger, Henrik, Gago-Dominguez, Manuela, Gao, Yu-Tang, García-Closas, Montserrat, García-Sáenz, José A, Genkinger, Jeanine, Gentry-Maharaj, Aleksandra, Grassmann, Felix, Guénel, Pascal, Gündert, Melanie, Haeberle, Lothar, Hahnen, Eric, Haiman, Christopher A, Håkansson, Niclas, Hall, Per, Harkness, Elaine F, Harrington, Patricia A, Hartikainen, Jaana M, Hartman, Mikael, Hein, Alexander, Ho, Weang-Kee, Hooning, Maartje J, Hoppe, Reiner, Hopper, John L, Houlston, Richard S, Howell, Anthony, Hunter, David J, Huo, Dezheng, ABCTB Investigators, Ito, Hidemi, Iwasaki, Motoki, Jakubowska, Anna, Janni, Wolfgang, John, Esther M, Jones, Michael E, Jung, Audrey, Kaaks, Rudolf, Kang, Daehee, Khusnutdinova, Elza K, Kim, Sung-Won, Kitahara, Cari M, Koutros, Stella, Kraft, Peter, Kristensen, Vessela N, Kubelka-Sabit, Katerina, Kurian, Allison W, and Kwong, Ava
Abstract: Low-frequency variants play an important role in breast cancer (BC) susceptibility. Gene-based methods can increase power by combining multiple variants in the same gene and help identify target genes. We evaluated the potential of gene-based aggregation in the Breast Cancer Association Consortium cohorts including 83,471 cases and 59,199 controls. Low-frequency variants were aggregated for individual genes' coding and regulatory regions. Association results in European ancestry samples were compared to single-marker association results in the same cohort. Gene-based associations were also combined in meta-analysis across individuals with European, Asian, African, and Latin American and Hispanic ancestry. In European ancestry samples, 14 genes were significantly associated (q < 0.05) with BC. Of those, two genes, FMNL3 (P = 6.11 × 10-6) and AC058822.1 (P = 1.47 × 10-4), represent new associations. High FMNL3 expression has previously been linked to poor prognosis in several other cancers. Meta-analysis of samples with diverse ancestry discovered further associations including established candidate genes ESR1 and CBLB. Furthermore, literature review and database query found further support for a biologically plausible link with cancer for genes CBLB, FMNL3, FGFR2, LSP1, MAP3K1, and SRGAP2C. Using extended gene-based aggregation tests including coding and regulatory variation, we report identification of plausible target genes for previously identified single-marker associations with BC as well as the discovery of novel genes implicated in BC development. Including multi ancestral cohorts in this study enabled the identification of otherwise missed disease associations as ESR1 (P = 1.31 × 10-5), demonstrating the importance of diversifying study cohorts.
Published: 2023

155. Increased FOXJ1 protein expression is associated with improved overall survival in high-grade serous ovarian carcinoma: an Ovarian Tumor Tissue Analysis Consortium Study.

Author: Weir, Ashley, Weir, Ashley, Kang, Eun-Young, Meagher, Nicola S, Nelson, Gregg S, Ghatage, Prafull, Lee, Cheng-Han, Riggan, Marjorie J, Gentry-Maharaj, Aleksandra, Ryan, Andy, Singh, Naveena, Widschwendter, Martin, Alsop, Jennifer, Anglesio, Michael S, Beckmann, Matthias W, Berger, Jessica, Bisinotto, Christiani, Boros, Jessica, Brand, Alison H, Brenton, James D, Brooks-Wilson, Angela, Carney, Michael E, Cunningham, Julie M, Cushing-Haugen, Kara L, Cybulski, Cezary, Elishaev, Esther, Erber, Ramona, Fereday, Sian, Fischer, Anna, Paz-Ares, Luis, Gayarre, Javier, Gilks, Blake C, Grube, Marcel, Harnett, Paul R, Harris, Holly R, Hartmann, Arndt, Hein, Alexander, Hendley, Joy, Hernandez, Brenda Y, Heublein, Sabine, Huang, Yajue, Huzarski, Tomasz, Jakubowska, Anna, Jimenez-Linan, Mercedes, Kennedy, Catherine J, Kommoss, Felix KF, Koziak, Jennifer M, Kraemer, Bernhard, Le, Nhu D, Lesnock, Jaime, Lester, Jenny, Lubiński, Jan, Menkiszak, Janusz, Ney, Britta, Olawaiye, Alexander, Orsulic, Sandra, Osorio, Ana, Robles-Díaz, Luis, Ruebner, Matthias, Shah, Mitul, Sharma, Raghwa, Shvetsov, Yurii B, Steed, Helen, Talhouk, Aline, Taylor, Sarah E, Traficante, Nadia, Vierkant, Robert A, Wang, Chen, Wilkens, Lynne R, Winham, Stacey J, Benitez, Javier, Berchuck, Andrew, Bowtell, David D, Candido Dos Reis, Francisco J, Cook, Linda S, DeFazio, Anna, AOCs group, Doherty, Jennifer A, Fasching, Peter A, García, María J, Goode, Ellen L, Goodman, Marc T, Gronwald, Jacek, Huntsman, David G, Karlan, Beth Y, Kommoss, Stefan, Modugno, Francesmary, Schildkraut, Joellen M, Sinn, Hans-Peter, Staebler, Annette, Kelemen, Linda E, Ford, Caroline E, Menon, Usha, Pharoah, Paul DP, Köbel, Martin, Ramus, Susan J, Weir, Ashley, Weir, Ashley, Kang, Eun-Young, Meagher, Nicola S, Nelson, Gregg S, Ghatage, Prafull, Lee, Cheng-Han, Riggan, Marjorie J, Gentry-Maharaj, Aleksandra, Ryan, Andy, Singh, Naveena, Widschwendter, Martin, Alsop, Jennifer, Anglesio, Michael S, Beckmann, Matthias W, Berger, Jessica, Bisinotto, Christiani, Boros, Jessica, Brand, Alison H, Brenton, James D, Brooks-Wilson, Angela, Carney, Michael E, Cunningham, Julie M, Cushing-Haugen, Kara L, Cybulski, Cezary, Elishaev, Esther, Erber, Ramona, Fereday, Sian, Fischer, Anna, Paz-Ares, Luis, Gayarre, Javier, Gilks, Blake C, Grube, Marcel, Harnett, Paul R, Harris, Holly R, Hartmann, Arndt, Hein, Alexander, Hendley, Joy, Hernandez, Brenda Y, Heublein, Sabine, Huang, Yajue, Huzarski, Tomasz, Jakubowska, Anna, Jimenez-Linan, Mercedes, Kennedy, Catherine J, Kommoss, Felix KF, Koziak, Jennifer M, Kraemer, Bernhard, Le, Nhu D, Lesnock, Jaime, Lester, Jenny, Lubiński, Jan, Menkiszak, Janusz, Ney, Britta, Olawaiye, Alexander, Orsulic, Sandra, Osorio, Ana, Robles-Díaz, Luis, Ruebner, Matthias, Shah, Mitul, Sharma, Raghwa, Shvetsov, Yurii B, Steed, Helen, Talhouk, Aline, Taylor, Sarah E, Traficante, Nadia, Vierkant, Robert A, Wang, Chen, Wilkens, Lynne R, Winham, Stacey J, Benitez, Javier, Berchuck, Andrew, Bowtell, David D, Candido Dos Reis, Francisco J, Cook, Linda S, DeFazio, Anna, AOCs group, Doherty, Jennifer A, Fasching, Peter A, García, María J, Goode, Ellen L, Goodman, Marc T, Gronwald, Jacek, Huntsman, David G, Karlan, Beth Y, Kommoss, Stefan, Modugno, Francesmary, Schildkraut, Joellen M, Sinn, Hans-Peter, Staebler, Annette, Kelemen, Linda E, Ford, Caroline E, Menon, Usha, Pharoah, Paul DP, Köbel, Martin, and Ramus, Susan J
Abstract: BackgroundRecently, we showed a >60% difference in 5-year survival for patients with tubo-ovarian high-grade serous carcinoma (HGSC) when stratified by a 101-gene mRNA expression prognostic signature. Given the varied patient outcomes, this study aimed to translate prognostic mRNA markers into protein expression assays by immunohistochemistry and validate their survival association in HGSC.MethodsTwo prognostic genes, FOXJ1 and GMNN, were selected based on high-quality antibodies, correlation with protein expression and variation in immunohistochemical scores in a preliminary cohort (n = 134 and n = 80, respectively). Six thousand four hundred and thirty-four (FOXJ1) and 5470 (GMNN) formalin-fixed, paraffin-embedded ovarian neoplasms (4634 and 4185 HGSC, respectively) represented on tissue microarrays from the Ovarian Tumor Tissue Analysis consortium underwent immunohistochemical staining and scoring, then univariate and multivariate survival analysis.ResultsConsistent with mRNA, FOXJ1 protein expression exhibited a linear, increasing association with improved overall survival in HGSC patients. Women with >50% expression had the most favourable outcomes (HR = 0.78, 95% CI 0.67-0.91, p < 0.0001). GMNN protein expression was not significantly associated with overall HSGC patient survival. However, HGSCs with >35% GMNN expression showed a trend for better outcomes, though this was not significant.ConclusionWe provide foundational evidence for the prognostic value of FOXJ1 in HGSC, validating the prior mRNA-based prognostic association by immunohistochemistry.
Published: 2023

156. Lifetime ovulatory years and risk of epithelial ovarian cancer: a multinational pooled analysis.

Author: Bandera, Elisa, Bandera, Elisa, Beckmann, Matthias, Berchuck, Andrew, Brooks-Wilson, Angela, Chang-Claude, Jenny, Cook, Linda, Cramer, Daniel, Cushing-Haugen, Kara, Doherty, Jennifer, Ekici, Arif, Fasching, Peter, Fortner, Renée, Gayther, Simon, Gentry-Maharaj, Aleksandra, Giles, Graham, Goode, Ellen, Goodman, Marc, Harris, Holly, Hein, Alexander, Kaaks, Rudolf, Kiemeney, Lambertus, Köbel, Martin, Kotsopoulos, Joanne, Le, Nhu, Lee, Alice, Matsuo, Keitaro, McGuire, Valerie, McLaughlin, John, Menon, Usha, Milne, Roger, Moysich, Kirsten, Pearce, Celeste, Pike, Malcolm, Qin, Bo, Ramus, Susan, Riggan, Marjorie, Rothstein, Joseph, Schildkraut, Joellen, Sieh, Weiva, Sutphen, Rebecca, Terry, Kathryn, Thompson, Pamela, Titus, Linda, van Altena, Anne, White, Emily, Whittemore, Alice, Wu, Anna, Zheng, Wei, Fu, Zhuxuan, Brooks, Maria, Irvin, Sarah, Jordan, Susan, Aben, Katja, Taylor, Sarah, Tang, Lu, Songer, Thomas, Wentzensen, Nicolas, Webb, Penelope, Risch, Harvey, Modugno, Francesmary, Anton-Culver, Hoda, Ziogas, Argyrios, Bandera, Elisa, Bandera, Elisa, Beckmann, Matthias, Berchuck, Andrew, Brooks-Wilson, Angela, Chang-Claude, Jenny, Cook, Linda, Cramer, Daniel, Cushing-Haugen, Kara, Doherty, Jennifer, Ekici, Arif, Fasching, Peter, Fortner, Renée, Gayther, Simon, Gentry-Maharaj, Aleksandra, Giles, Graham, Goode, Ellen, Goodman, Marc, Harris, Holly, Hein, Alexander, Kaaks, Rudolf, Kiemeney, Lambertus, Köbel, Martin, Kotsopoulos, Joanne, Le, Nhu, Lee, Alice, Matsuo, Keitaro, McGuire, Valerie, McLaughlin, John, Menon, Usha, Milne, Roger, Moysich, Kirsten, Pearce, Celeste, Pike, Malcolm, Qin, Bo, Ramus, Susan, Riggan, Marjorie, Rothstein, Joseph, Schildkraut, Joellen, Sieh, Weiva, Sutphen, Rebecca, Terry, Kathryn, Thompson, Pamela, Titus, Linda, van Altena, Anne, White, Emily, Whittemore, Alice, Wu, Anna, Zheng, Wei, Fu, Zhuxuan, Brooks, Maria, Irvin, Sarah, Jordan, Susan, Aben, Katja, Taylor, Sarah, Tang, Lu, Songer, Thomas, Wentzensen, Nicolas, Webb, Penelope, Risch, Harvey, Modugno, Francesmary, Anton-Culver, Hoda, and Ziogas, Argyrios
Abstract: BACKGROUND: The role of ovulation in epithelial ovarian cancer (EOC) is supported by the consistent protective effects of parity and oral contraceptive use. Whether these factors protect through anovulation alone remains unclear. We explored the association between lifetime ovulatory years (LOY) and EOC. METHODS: LOY was calculated using 12 algorithms. Odds ratios (ORs) and 95% confidence intervals (CIs) estimated the association between LOY or LOY components and EOC among 26 204 control participants and 21 267 case patients from 25 studies. To assess whether LOY components act through ovulation suppression alone, we compared beta coefficients obtained from regression models with expected estimates assuming 1 year of ovulation suppression has the same effect regardless of source. RESULTS: LOY was associated with increased EOC risk (OR per year increase = 1.014, 95% CI = 1.009 to 1.020 to OR per year increase = 1.044, 95% CI = 1.041 to 1.048). Individual LOY components, except age at menarche, also associated with EOC. The estimated model coefficient for oral contraceptive use and pregnancies were 4.45 times and 12- to 15-fold greater than expected, respectively. LOY was associated with high-grade serous, low-grade serous, endometrioid, and clear cell histotypes (ORs per year increase = 1.054, 1.040, 1.065, and 1.098, respectively) but not mucinous tumors. Estimated coefficients of LOY components were close to expected estimates for high-grade serous but larger than expected for low-grade serous, endometrioid, and clear cell histotypes. CONCLUSIONS: LOY is positively associated with nonmucinous EOC. Differences between estimated and expected model coefficients for LOY components suggest factors beyond ovulation underlie the associations between LOY components and EOC in general and for non-HGSOC.
Published: 2023

157. A Likelihood Ratio Approach for Utilizing Case-Control Data in the Clinical Classification of Rare Sequence Variants : Application to BRCA1 and BRCA2

Author: Zanti, Maria, O'Mahony, Denise G., Parsons, Michael T., Li, Hongyan, Dennis, Joe, Aittomakkiki, Kristiina, Andrulis, Irene L., Anton-Culver, Hoda, Aronson, Kristan J., Augustinsson, Annelie, Becher, Heiko, Bojesen, Stig E., Bolla, Manjeet K., Brenner, Hermann, Brown, Melissa A., Buys, Saundra S., Canzian, Federico, Caputo, Sandrine M., Castelao, Jose E., Chang-Claude, Jenny, Czene, Kamila, Daly, Mary B., De Nicolo, Arcangela, Devilee, Peter, Dork, Thilo, Dunning, Alison M., Dwek, Miriam, Eccles, Diana M., Engel, Christoph, Evans, D. Gareth, Fasching, Peter A., Gago-Dominguez, Manuela, Garcia-Closas, Montserrat, Garcia-Saenz, Jose A., Gentry-Maharaj, Aleksandra, Geurts-Giele, Willemina R. R., Giles, Graham G., Glendon, Gord, Goldberg, Mark S., Garcia, Encarna B. Gomez, Guendert, Melanie, Guenel, Pascal, Hahnen, Eric, Haiman, Christopher A., Hall, Per, Hamann, Ute, Harkness, Elaine F., Hogervorst, Frans B. L., Hollestelle, Antoinette, Hoppe, Reiner, Hopper, John L., Houdayer, Claude, Houlston, Richard S., Howell, Anthony, Investigators, Abctb, Jakimovska, Milena, Jakubowska, Anna, Jernstrom, Helena, John, Esther M., Kaaks, Rudolf, Kitahara, Cari M., Koutros, Stella, Kraft, Peter, Kristensen, Vessela N., Lacey, James, V, Lambrechts, Diether, Leone, Melanie, Lindblom, Annika, Lush, Michael, Mannermaa, Arto, Manoochehri, Mehdi, Manoukian, Siranoush, Margolin, Sara, Martinez, Maria Elena, Menon, Usha, Milne, Roger L., Monteiro, Alvaro N., Murphy, Rachel A., Neuhausen, Susan L., Nevanlinna, Heli, Newman, William G., Offit, Kenneth, Park, Sue K., James, Paul, Peterlongo, Paolo, Peto, Julian, Plaseska-Karanfilska, Dijana, Punie, Kevin, Radice, Paolo, Rashid, Muhammad U., Rennert, Gad, Romero, Atocha, Rosenberg, Efraim H., Saloustros, Emmanouil, Sandler, Dale P., Schmidt, Marjanka K., Schmutzler, Rita K., Shu, Xiao-Ou, Simard, Jacques, Southey, Melissa C., Stone, Jennifer, Stoppa-Lyonnet, Dominique, Tamimi, Rulla M., Tapper, William J., Taylor, Jack A., Teo, Soo Hwang, Teras, Lauren R., Terry, Mary Beth, Thomassen, Mads, Troester, Melissa A., Vachon, Celine M., Vega, Ana, Vreeswijk, Maaike P. G., Wang, Qin, Wappenschmidt, Barbara, Weinberg, Clarice R., Wolk, Alicja, Zheng, Wei, Feng, Bingjian, Couch, Fergus J., Spurdle, Amanda B., Easton, Douglas F., Goldgar, David E., Michailidou, Kyriaki, Zanti, Maria, O'Mahony, Denise G., Parsons, Michael T., Li, Hongyan, Dennis, Joe, Aittomakkiki, Kristiina, Andrulis, Irene L., Anton-Culver, Hoda, Aronson, Kristan J., Augustinsson, Annelie, Becher, Heiko, Bojesen, Stig E., Bolla, Manjeet K., Brenner, Hermann, Brown, Melissa A., Buys, Saundra S., Canzian, Federico, Caputo, Sandrine M., Castelao, Jose E., Chang-Claude, Jenny, Czene, Kamila, Daly, Mary B., De Nicolo, Arcangela, Devilee, Peter, Dork, Thilo, Dunning, Alison M., Dwek, Miriam, Eccles, Diana M., Engel, Christoph, Evans, D. Gareth, Fasching, Peter A., Gago-Dominguez, Manuela, Garcia-Closas, Montserrat, Garcia-Saenz, Jose A., Gentry-Maharaj, Aleksandra, Geurts-Giele, Willemina R. R., Giles, Graham G., Glendon, Gord, Goldberg, Mark S., Garcia, Encarna B. Gomez, Guendert, Melanie, Guenel, Pascal, Hahnen, Eric, Haiman, Christopher A., Hall, Per, Hamann, Ute, Harkness, Elaine F., Hogervorst, Frans B. L., Hollestelle, Antoinette, Hoppe, Reiner, Hopper, John L., Houdayer, Claude, Houlston, Richard S., Howell, Anthony, Investigators, Abctb, Jakimovska, Milena, Jakubowska, Anna, Jernstrom, Helena, John, Esther M., Kaaks, Rudolf, Kitahara, Cari M., Koutros, Stella, Kraft, Peter, Kristensen, Vessela N., Lacey, James, V, Lambrechts, Diether, Leone, Melanie, Lindblom, Annika, Lush, Michael, Mannermaa, Arto, Manoochehri, Mehdi, Manoukian, Siranoush, Margolin, Sara, Martinez, Maria Elena, Menon, Usha, Milne, Roger L., Monteiro, Alvaro N., Murphy, Rachel A., Neuhausen, Susan L., Nevanlinna, Heli, Newman, William G., Offit, Kenneth, Park, Sue K., James, Paul, Peterlongo, Paolo, Peto, Julian, Plaseska-Karanfilska, Dijana, Punie, Kevin, Radice, Paolo, Rashid, Muhammad U., Rennert, Gad, Romero, Atocha, Rosenberg, Efraim H., Saloustros, Emmanouil, Sandler, Dale P., Schmidt, Marjanka K., Schmutzler, Rita K., Shu, Xiao-Ou, Simard, Jacques, Southey, Melissa C., Stone, Jennifer, Stoppa-Lyonnet, Dominique, Tamimi, Rulla M., Tapper, William J., Taylor, Jack A., Teo, Soo Hwang, Teras, Lauren R., Terry, Mary Beth, Thomassen, Mads, Troester, Melissa A., Vachon, Celine M., Vega, Ana, Vreeswijk, Maaike P. G., Wang, Qin, Wappenschmidt, Barbara, Weinberg, Clarice R., Wolk, Alicja, Zheng, Wei, Feng, Bingjian, Couch, Fergus J., Spurdle, Amanda B., Easton, Douglas F., Goldgar, David E., and Michailidou, Kyriaki
Abstract: A large number of variants identified through clinical genetic testing in disease susceptibility genes are of uncertain significance (VUS). Following the recommendations of the American College of Medical Genetics and Genomics (ACMG) and Association for Molecular Pathology (AMP), the frequency in case-control datasets (PS4 criterion) can inform their interpretation. We present a novel case-control likelihood ratio-based method that incorporates gene-specific age-related penetrance. We demonstrate the utility of this method in the analysis of simulated and real datasets. In the analysis of simulated data, the likelihood ratio method was more powerful compared to other methods. Likelihood ratios were calculated for a case-control dataset of BRCA1 and BRCA2 variants from the Breast Cancer Association Consortium (BCAC) and compared with logistic regression results. A larger number of variants reached evidence in favor of pathogenicity, and a substantial number of variants had evidence against pathogenicity-findings that would not have been reached using other case-control analysis methods. Our novel method provides greater power to classify rare variants compared with classical case-control methods. As an initiative from the ENIGMA Analytical Working Group, we provide user-friendly scripts and preformatted Excel calculators for implementation of the method for rare variants in BRCA1, BRCA2, and other high-risk genes with known penetrance.
Published: 2023
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158. A likelihood ratio approach for utilizing case-control data in the clinical classification of rare sequence variants:Application to BRCA1 and BRCA2

Author: Zanti, Maria, O'Mahony, Denise G., Parsons, Michael T., Li, Hongyan, Dennis, Joe, Aittomäkkiki, Kristiina, Andrulis, Irene L., Anton-Culver, Hoda, Aronson, Kristan J., Augustinsson, Annelie, Becher, Heiko, Bojesen, Stig E., Bolla, Manjeet K., Brenner, Hermann, Brown, Melissa A., Buys, Saundra S., Canzian, Federico, Caputo, Sandrine M., Castelao, Jose E., Chang-Claude, Jenny, Czene, Kamila, Daly, Mary B., De Nicolo, Arcangela, Devilee, Peter, Dörk, Thilo, Dunning, Alison M., Dwek, Miriam, Eccles, Diana M., Engel, Christoph, Gareth Evans, D., Fasching, Peter A., Gago-Dominguez, Manuela, García-Closas, Montserrat, García-Sáenz, José A., Gentry-Maharaj, Aleksandra, Geurts-Giele, Willemina R.R., Giles, Graham G., Glendon, Gord, Goldberg, Mark S., Gómez Garcia, Encarna B., Göendert, Melanie, Guénel, Pascal, Hahnen, Eric, Haiman, Christopher A., Hall, Per, Hamann, Ute, Harkness, Elaine F., Hogervorst, Frans B.L., Hollestelle, Antoinette, Hoppe, Reiner, Hopper, John L., Houdayer, Claude, Houlston, Richard S., Howell, Anthony, Jakimovska, Milena, Jakubowska, Anna, Jernström, Helena, John, Esther M., Kaaks, Rudolf, Kitahara, Cari M., Koutros, Stella, Kraft, Peter, Kristensen, Vessela N., Lacey, James V., Lambrechts, Diether, Léoné, Melanie, Lindblom, Annika, Lubiski, Jan, Lush, Michael, Mannermaa, Arto, Manoochehri, Mehdi, Manoukian, Siranoush, Margolin, Sara, Martinez, Maria Elena, Menon, Usha, Milne, Roger L., Monteiro, Alvaro N., Murphy, Rachel A., Neuhausen, Susan L., Nevanlinna, Heli, Newman, William G., Offit, Kenneth, Park, Sue K., James, Paul, Peterlongo, Paolo, Peto, Julian, Plaseska-Karanfilska, Dijana, Punie, Kevin, Radice, Paolo, Rashid, Muhammad U., Rennert, Gad, Romero, Atocha, Rosenberg, Efraim H., Saloustros, Emmanouil, Sandler, Dale P., Schmidt, Marjanka K., Schmutzler, Rita K., Shu, Xiao Ou, Simard, Jacques, Southey, Melissa C., Stone, Jennifer, Stoppa-Lyonnet, Dominique, Tamimi, Rulla M., Tapper, William J., Taylor, Jack A., Teo, Soo Hwang, Teras, Lauren R., Terry, Mary Beth, Thomassen, Mads, Troester, Melissa A., Vachon, Celine M., Vega, Ana, Vreeswijk, Maaike P.G., Wang, Qin, Wappenschmidt, Barbara, Weinberg, Clarice R., Wolk, Alicja, Zheng, Wei, Feng, Bingjian, Couch, Fergus J., Spurdle, Amanda B., Easton, Douglas F., Goldgar, David E., Michailidou, Kyriaki, Zanti, Maria, O'Mahony, Denise G., Parsons, Michael T., Li, Hongyan, Dennis, Joe, Aittomäkkiki, Kristiina, Andrulis, Irene L., Anton-Culver, Hoda, Aronson, Kristan J., Augustinsson, Annelie, Becher, Heiko, Bojesen, Stig E., Bolla, Manjeet K., Brenner, Hermann, Brown, Melissa A., Buys, Saundra S., Canzian, Federico, Caputo, Sandrine M., Castelao, Jose E., Chang-Claude, Jenny, Czene, Kamila, Daly, Mary B., De Nicolo, Arcangela, Devilee, Peter, Dörk, Thilo, Dunning, Alison M., Dwek, Miriam, Eccles, Diana M., Engel, Christoph, Gareth Evans, D., Fasching, Peter A., Gago-Dominguez, Manuela, García-Closas, Montserrat, García-Sáenz, José A., Gentry-Maharaj, Aleksandra, Geurts-Giele, Willemina R.R., Giles, Graham G., Glendon, Gord, Goldberg, Mark S., Gómez Garcia, Encarna B., Göendert, Melanie, Guénel, Pascal, Hahnen, Eric, Haiman, Christopher A., Hall, Per, Hamann, Ute, Harkness, Elaine F., Hogervorst, Frans B.L., Hollestelle, Antoinette, Hoppe, Reiner, Hopper, John L., Houdayer, Claude, Houlston, Richard S., Howell, Anthony, Jakimovska, Milena, Jakubowska, Anna, Jernström, Helena, John, Esther M., Kaaks, Rudolf, Kitahara, Cari M., Koutros, Stella, Kraft, Peter, Kristensen, Vessela N., Lacey, James V., Lambrechts, Diether, Léoné, Melanie, Lindblom, Annika, Lubiski, Jan, Lush, Michael, Mannermaa, Arto, Manoochehri, Mehdi, Manoukian, Siranoush, Margolin, Sara, Martinez, Maria Elena, Menon, Usha, Milne, Roger L., Monteiro, Alvaro N., Murphy, Rachel A., Neuhausen, Susan L., Nevanlinna, Heli, Newman, William G., Offit, Kenneth, Park, Sue K., James, Paul, Peterlongo, Paolo, Peto, Julian, Plaseska-Karanfilska, Dijana, Punie, Kevin, Radice, Paolo, Rashid, Muhammad U., Rennert, Gad, Romero, Atocha, Rosenberg, Efraim H., Saloustros, Emmanouil, Sandler, Dale P., Schmidt, Marjanka K., Schmutzler, Rita K., Shu, Xiao Ou, Simard, Jacques, Southey, Melissa C., Stone, Jennifer, Stoppa-Lyonnet, Dominique, Tamimi, Rulla M., Tapper, William J., Taylor, Jack A., Teo, Soo Hwang, Teras, Lauren R., Terry, Mary Beth, Thomassen, Mads, Troester, Melissa A., Vachon, Celine M., Vega, Ana, Vreeswijk, Maaike P.G., Wang, Qin, Wappenschmidt, Barbara, Weinberg, Clarice R., Wolk, Alicja, Zheng, Wei, Feng, Bingjian, Couch, Fergus J., Spurdle, Amanda B., Easton, Douglas F., Goldgar, David E., and Michailidou, Kyriaki
Abstract: A large number of variants identified through clinical genetic testing in disease susceptibility genes are of uncertain significance (VUS). Following the recommendations of the American College of Medical Genetics and Genomics (ACMG) and Association for Molecular Pathology (AMP), the frequency in case-control datasets (PS4 criterion) can inform their interpretation. We present a novel case-control likelihood ratio-based method that incorporates gene-specific age-related penetrance. We demonstrate the utility of this method in the analysis of simulated and real datasets. In the analysis of simulated data, the likelihood ratio method was more powerful compared to other methods. Likelihood ratios were calculated for a case-control dataset of BRCA1 and BRCA2 variants from the Breast Cancer Association Consortium (BCAC) and compared with logistic regression results. A larger number of variants reached evidence in favor of pathogenicity, and a substantial number of variants had evidence against pathogenicity findings that would not have been reached using other case-control analysis methods. Our novel method provides greater power to classify rare variants compared with classical case-control methods. As an initiative from the ENIGMA Analytical Working Group, we provide user-friendly scripts and preformatted Excel calculators for implementation of the method for rare variants in BRCA1, BRCA2, and other high-risk genes with known penetrance.
Published: 2023

159. Thromboxane biosynthesis in cancer patients and its inhibition by aspirin: a sub-study of the Add-Aspirin trial

Author: Joharatnam-Hogan, Nalinie, Hatem, Duaa, Cafferty, Fay H, Petrucci, Giovanna, Cameron, David A, Ring, Alistair, Kynaston, Howard G, Gilbert, Duncan C, Wilson, Richard H, Hubner, Richard A, Swinson, Daniel E B, Cleary, Siobhan, Robbins, Alex, Mackenzie, Mairead, Scott-Brown, Martin W G, Sothi, Sharmila, Dawson, Lesley K, Capaldi, Lisa M, Churn, Mark, Cunningham, David, Khoo, Vincent, Armstrong, Anne C, Ainsworth, Nicola L, Horan, Gail, Wheatley, Duncan A, Mullen, Russell, Lofts, Fiona J, Walther, Axel, Herbertson, Rebecca A, Eaton, John D, O'Callaghan, Ann, Eichholz, Andrew, Kagzi, Mohammed M, Patterson, Daniel M, Narahari, Krishna, Bradbury, Jennifer, Stokes, Zuzana, Rizvi, Azhar J, Walker, Georgina A, Kunene, Victoria L, Srihari, Narayanan, Gentry-Maharaj, Aleksandra, Meade, Angela, Patrono, Carlo, Rocca, Bianca, Langley, Ruth E, Petrucci, Giovanna (ORCID:0000-0002-9280-3673), Rocca, Bianca (ORCID:0000-0001-8304-6423), Joharatnam-Hogan, Nalinie, Hatem, Duaa, Cafferty, Fay H, Petrucci, Giovanna, Cameron, David A, Ring, Alistair, Kynaston, Howard G, Gilbert, Duncan C, Wilson, Richard H, Hubner, Richard A, Swinson, Daniel E B, Cleary, Siobhan, Robbins, Alex, Mackenzie, Mairead, Scott-Brown, Martin W G, Sothi, Sharmila, Dawson, Lesley K, Capaldi, Lisa M, Churn, Mark, Cunningham, David, Khoo, Vincent, Armstrong, Anne C, Ainsworth, Nicola L, Horan, Gail, Wheatley, Duncan A, Mullen, Russell, Lofts, Fiona J, Walther, Axel, Herbertson, Rebecca A, Eaton, John D, O'Callaghan, Ann, Eichholz, Andrew, Kagzi, Mohammed M, Patterson, Daniel M, Narahari, Krishna, Bradbury, Jennifer, Stokes, Zuzana, Rizvi, Azhar J, Walker, Georgina A, Kunene, Victoria L, Srihari, Narayanan, Gentry-Maharaj, Aleksandra, Meade, Angela, Patrono, Carlo, Rocca, Bianca, Langley, Ruth E, Petrucci, Giovanna (ORCID:0000-0002-9280-3673), and Rocca, Bianca (ORCID:0000-0001-8304-6423)
Abstract: BACKGROUND: Pre-clinical models demonstrate that platelet activation is involved in the spread of malignancy. Ongoing clinical trials are assessing whether aspirin, which inhibits platelet activation, can prevent or delay metastases.METHODS: Urinary 11-dehydro-thromboxane B2 (U-TXM), a biomarker of in vivo platelet activation, was measured after radical cancer therapy and correlated with patient demographics, tumour type, recent treatment, and aspirin use (100 mg, 300 mg or placebo daily) using multivariable linear regression models with log-transformed values.RESULTS: In total, 716 patients (breast 260, colorectal 192, gastro-oesophageal 53, prostate 211) median age 61 years, 50% male were studied. Baseline median U-TXM were breast 782; colorectal 1060; gastro-oesophageal 1675 and prostate 826 pg/mg creatinine; higher than healthy individuals (similar to 500 pg/mg creatinine). Higher levels were associated with raised body mass index, inflammatory markers, and in the colorectal and gastro-oesophageal participants compared to breast participants (P < 0.001) independent of other baseline characteristics. Aspirin 100 mg daily decreased U-TXM similarly across all tumour types (median reductions: 77-82%). Aspirin 300 mg daily provided no additional suppression of U-TXM compared with 100 mg.CONCLUSIONS: Persistently increased thromboxane biosynthesis was detected after radical cancer therapy, particularly in colorectal and gastro-oesophageal patients. Thromboxane biosynthesis should be explored further as a biomarker of active malignancy and may identify patients likely to benefit from aspirin.
Published: 2023

160. No clinical utility of KRAS variant rs61764370 for ovarian or breast cancer

Author: Hollestelle, Antoinette, van der Baan, Frederieke H., Berchuck, Andrew, Johnatty, Sharon E., Aben, Katja K., Agnarsson, Bjarni A., Aittomäki, Kristiina, Alducci, Elisa, Andrulis, Irene L., Anton-Culver, Hoda, Antonenkova, Natalia N., Antoniou, Antonis C., Apicella, Carmel, Arndt, Volker, Arnold, Norbert, Arun, Banu K., Arver, Brita, Ashworth, Alan, Baglietto, Laura, Balleine, Rosemary, Bandera, Elisa V., Barrowdale, Daniel, Bean, Yukie T., Beckmann, Lars, Beckmann, Matthias W., Benitez, Javier, Berger, Andreas, Berger, Raanan, Beuselinck, Benoit, Bisogna, Maria, Bjorge, Line, Blomqvist, Carl, Bogdanova, Natalia V., Bojesen, Anders, Bojesen, Stig E., Bolla, Manjeet K., Bonanni, Bernardo, Brand, Judith S., Brauch, Hiltrud, Brenner, Hermann, Brinton, Louise, Brooks-Wilson, Angela, Bruinsma, Fiona, Brunet, Joan, Brüning, Thomas, Budzilowska, Agnieszka, Bunker, Clareann H., Burwinkel, Barbara, Butzow, Ralf, Buys, Saundra S., Caligo, Maria A., Campbell, Ian, Carter, Jonathan, Chang-Claude, Jenny, Chanock, Stephen J., Claes, Kathleen B.M., Collée, J. Margriet, Cook, Linda S., Couch, Fergus J., Cox, Angela, Cramer, Daniel, Cross, Simon S., Cunningham, Julie M., Cybulski, Cezary, Czene, Kamila, Damiola, Francesca, Dansonka-Mieszkowska, Agnieszka, Darabi, Hatef, de la Hoya, Miguel, deFazio, Anna, Dennis, Joseph, Devilee, Peter, Dicks, Ed M., Diez, Orland, Doherty, Jennifer A., Domchek, Susan M., Dorfling, Cecilia M., Dörk, Thilo, Silva, Isabel Dos Santos, du Bois, Andreas, Dumont, Martine, Dunning, Alison M., Duran, Mercedes, Easton, Douglas F., Eccles, Diana, Edwards, Robert P., Ehrencrona, Hans, Ejlertsen, Bent, Ekici, Arif B., Ellis, Steve D., Engel, Christoph, Eriksson, Mikael, Fasching, Peter A., Feliubadalo, Lidia, Figueroa, Jonine, Flesch-Janys, Dieter, Fletcher, Olivia, Fontaine, Annette, Fortuzzi, Stefano, Fostira, Florentia, Fridley, Brooke L., Friebel, Tara, Friedman, Eitan, Friel, Grace, Frost, Debra, Garber, Judy, García-Closas, Montserrat, Gayther, Simon A., Gentry-Maharaj, Aleksandra, Gerdes, Anne-Marie, Giles, Graham G., Glasspool, Rosalind, Glendon, Gord, Godwin, Andrew K., Goodman, Marc T., Gore, Martin, Greene, Mark H., Grip, Mervi, Gronwald, Jacek, Gschwantler Kaulich, Daphne, Guénel, Pascal, Guzman, Starr R., Haeberle, Lothar, Haiman, Christopher A., Hall, Per, Halverson, Sandra L., Hamann, Ute, Hansen, Thomas V.O., Harter, Philipp, Hartikainen, Jaana M., Healey, Sue, Hein, Alexander, Heitz, Florian, Henderson, Brian E., Herzog, Josef, T Hildebrandt, Michelle A., Høgdall, Claus K., Høgdall, Estrid, Hogervorst, Frans B.L., Hopper, John L., Humphreys, Keith, Huzarski, Tomasz, Imyanitov, Evgeny N., Isaacs, Claudine, Jakubowska, Anna, Janavicius, Ramunas, Jaworska, Katarzyna, Jensen, Allan, Jensen, Uffe Birk, Johnson, Nichola, Jukkola-Vuorinen, Arja, Kabisch, Maria, Karlan, Beth Y., Kataja, Vesa, Kauff, Noah, Kelemen, Linda E., Kerin, Michael J., Kiemeney, Lambertus A., Kjaer, Susanne K., Knight, Julia A., Knol-Bout, Jacoba P., Konstantopoulou, Irene, Kosma, Veli-Matti, Krakstad, Camilla, Kristensen, Vessela, Kuchenbaecker, Karoline B., Kupryjanczyk, Jolanta, Laitman, Yael, Lambrechts, Diether, Lambrechts, Sandrina, Larson, Melissa C., Lasa, Adriana, Laurent-Puig, Pierre, Lazaro, Conxi, Le, Nhu D., Le Marchand, Loic, Leminen, Arto, Lester, Jenny, Levine, Douglas A., Li, Jingmei, Liang, Dong, Lindblom, Annika, Lindor, Noralane, Lissowska, Jolanta, Long, Jirong, Lu, Karen H., Lubinski, Jan, Lundvall, Lene, Lurie, Galina, Mai, Phuong L., Mannermaa, Arto, Margolin, Sara, Mariette, Frederique, Marme, Frederik, Martens, John W.M., Massuger, Leon F.A.G., Maugard, Christine, Mazoyer, Sylvie, McGuffog, Lesley, McGuire, Valerie, McLean, Catriona, McNeish, Iain, Meindl, Alfons, Menegaux, Florence, Menéndez, Primitiva, Menkiszak, Janusz, Menon, Usha, Mensenkamp, Arjen R., Miller, Nicola, Milne, Roger L., Modugno, Francesmary, Montagna, Marco, Moysich, Kirsten B., Müller, Heiko, Mulligan, Anna Marie, Muranen, Taru A., Narod, Steven A., Nathanson, Katherine L., Ness, Roberta B., Neuhausen, Susan L., Nevanlinna, Heli, Neven, Patrick, Nielsen, Finn C., Nielsen, Sune F., Nordestgaard, Børge G., Nussbaum, Robert L., Odunsi, Kunle, Offit, Kenneth, Olah, Edith, Olopade, Olufunmilayo I., Olson, Janet E., Olson, Sara H., Oosterwijk, Jan C., Orlow, Irene, Orr, Nick, Orsulic, Sandra, Osorio, Ana, Ottini, Laura, Paul, James, Pearce, Celeste L., Pedersen, Inge Sokilde, Peissel, Bernard, Pejovic, Tanja, Pelttari, Liisa M., Perkins, Jo, Permuth-Wey, Jenny, Peterlongo, Paolo, Peto, Julian, Phelan, Catherine M., Phillips, Kelly-Anne, Piedmonte, Marion, Pike, Malcolm C., Platte, Radka, Plisiecka-Halasa, Joanna, Poole, Elizabeth M., Poppe, Bruce, Pylkäs, Katri, Radice, Paolo, Ramus, Susan J., Rebbeck, Timothy R., Reed, Malcolm W.R., Rennert, Gad, Risch, Harvey A., Robson, Mark, Rodriguez, Gustavo C., Romero, Atocha, Rossing, Mary Anne, Rothstein, Joseph H., Rudolph, Anja, Runnebaum, Ingo, Salani, Ritu, Salvesen, Helga B., Sawyer, Elinor J., Schildkraut, Joellen M., Schmidt, Marjanka K., Schmutzler, Rita K., Schneeweiss, Andreas, Schoemaker, Minouk J., Schrauder, Michael G., Schumacher, Fredrick, Schwaab, Ira, Scuvera, Giulietta, Sellers, Thomas A., Severi, Gianluca, Seynaeve, Caroline M., Shah, Mitul, Shrubsole, Martha, Siddiqui, Nadeem, Sieh, Weiva, Simard, Jacques, Singer, Christian F., Sinilnikova, Olga M., Smeets, Dominiek, Sohn, Christof, Soller, Maria, Song, Honglin, Soucy, Penny, Southey, Melissa C., Stegmaier, Christa, Stoppa-Lyonnet, Dominique, Sucheston, Lara, Swerdlow, Anthony, Tangen, Ingvild L., Tea, Muy-Kheng, Teixeira, Manuel R., Terry, Kathryn L., Terry, Mary Beth, Thomassen, Mads, Thompson, Pamela J., Tihomirova, Laima, Tischkowitz, Marc, Toland, Amanda Ewart, Tollenaar, Rob A.E.M., Tomlinson, Ian, Torres, Diana, Truong, Thérèse, Tsimiklis, Helen, Tung, Nadine, Tworoger, Shelley S., Tyrer, Jonathan P., Vachon, Celine M., Van 't Veer, Laura J., van Altena, Anne M., Van Asperen, C.J., van den Berg, David, van den Ouweland, Ans M.W., van Doorn, Helena C., Van Nieuwenhuysen, Els, van Rensburg, Elizabeth J., Vergote, Ignace, Verhoef, Senno, Vierkant, Robert A., Vijai, Joseph, Vitonis, Allison F., von Wachenfeldt, Anna, Walsh, Christine, Wang, Qin, Wang-Gohrke, Shan, Wappenschmidt, Barbara, Weischer, Maren, Weitzel, Jeffrey N., Weltens, Caroline, Wentzensen, Nicolas, Whittemore, Alice S., Wilkens, Lynne R., Winqvist, Robert, Wu, Anna H., Wu, Xifeng, Yang, Hannah P., Zaffaroni, Daniela, Pilar Zamora, M., Zheng, Wei, Ziogas, Argyrios, Chenevix-Trench, Georgia, Pharoah, Paul D.P., Rookus, Matti A., Hooning, Maartje J., and Goode, Ellen L.
Published: 2016
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161. Ovarian cancer screening and mortality in the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS): a randomised controlled trial

Author: Jacobs, Ian J, Menon, Usha, Ryan, Andy, Gentry-Maharaj, Aleksandra, Burnell, Matthew, Kalsi, Jatinderpal K, Amso, Nazar N, Apostolidou, Sophia, Benjamin, Elizabeth, Cruickshank, Derek, Crump, Danielle N, Davies, Susan K, Dawnay, Anne, Dobbs, Stephen, Fletcher, Gwendolen, Ford, Jeremy, Godfrey, Keith, Gunu, Richard, Habib, Mariam, Hallett, Rachel, Herod, Jonathan, Jenkins, Howard, Karpinskyj, Chloe, Leeson, Simon, Lewis, Sara J, Liston, William R, Lopes, Alberto, Mould, Tim, Murdoch, John, Oram, David, Rabideau, Dustin J, Reynolds, Karina, Scott, Ian, Seif, Mourad W, Sharma, Aarti, Singh, Naveena, Taylor, Julie, Warburton, Fiona, Widschwendter, Martin, Williamson, Karin, Woolas, Robert, Fallowfield, Lesley, McGuire, Alistair J, Campbell, Stuart, Parmar, Mahesh, and Skates, Steven J
Published: 2016
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162. Tumour stage, treatment, and survival of women with high-grade serous tubo-ovarian cancer in UKCTOCS: an exploratory analysis of a randomised controlled trial.

Author: Menon, Usha, Gentry-Maharaj, Aleksandra, Burnell, Matthew, Ryan, Andy, Singh, Naveena, Manchanda, Ranjit, Kalsi, Jatinderpal K, Woolas, Robert, Arora, Rupali, Casey, Laura, Dawnay, Anne, Sharma, Aarti, Williamson, Karin, Apostolidou, Sophia, Fallowfield, Lesley, McGuire, Alistair J, Campbell, Stuart, Skates, Steven J, Jacobs, Ian J, and Parmar, Mahesh K B
Subjects: *RANDOMIZED controlled trials, *CANCER diagnosis, *MEDICAL screening, *EARLY detection of cancer, *COMBINATION drug therapy, *CA 125 test, *INDUCED ovulation
Abstract: In UKCTOCS, there was a decrease in the diagnosis of advanced stage tubo-ovarian cancer but no reduction in deaths in the multimodal screening group compared with the no screening group. Therefore, we did exploratory analyses of patients with high-grade serous ovarian cancer to understand the reason for the discrepancy. UKCTOCS was a 13-centre randomised controlled trial of screening postmenopausal women from the general population, aged 50–74 years, with intact ovaries. The trial management system randomly allocated (2:1:1) eligible participants (recruited from April 17, 2001, to Sept 29, 2005) in blocks of 32 using computer generated random numbers to no screening or annual screening (multimodal screening or ultrasound screening) until Dec 31, 2011. Follow-up was through national registries until June 30, 2020. An outcome review committee, masked to randomisation group, adjudicated on ovarian cancer diagnosis, histotype, stage, and cause of death. In this study, analyses were intention-to-screen comparisons of women with high-grade serous cancer at censorship (Dec 31, 2014) in multimodal screening versus no screening, using descriptive statistics for stage and treatment endpoints, and the Versatile test for survival from randomisation. This trial is registered with the ISRCTN Registry, 22488978, and ClinicalTrials.gov , NCT00058032. 202 562 eligible women were recruited (50 625 multimodal screening; 50 623 ultrasound screening; 101 314 no screening). 259 (0·5%) of 50 625 participants in the multimodal screening group and 520 (0·5%) of 101 314 in the no screening group were diagnosed with high-grade serous cancer. In the multimodal screening group compared with the no screening group, fewer were diagnosed with advanced stage disease (195 [75%] of 259 vs 446 [86%] of 520; p=0·0003), more had primary surgery (158 [61%] vs 219 [42%]; p<0·0001), more had zero residual disease following debulking surgery (119 [46%] vs 157 [30%]; p<0·0001), and more received treatment including both surgery and chemotherapy (192 [74%] vs 331 [64%]; p=0·0032). There was no difference in the first-line combination chemotherapy rate (142 [55%] vs 293 [56%]; p=0·69). Median follow-up from randomisation of 779 women with high-grade serous cancer in the multimodal and no screening groups was 9·51 years (IQR 6·04–13·00). At censorship (June 30, 2020), survival from randomisation was longer in women with high-grade serous cancer in the multimodal screening group than in the no screening group with absolute difference in survival of 6·9% (95% CI 0·4–13·0; p=0·042) at 18 years (21% [95% CI 15·6–26·2] vs 14% [95% CI 10·5–17·4]). To our knowledge, this is the first evidence that screening can detect high-grade serous cancer earlier and lead to improved short-term treatment outcomes compared with no screening. The potential survival benefit for women with high-grade serous cancer was small, most likely due to only modest gains in early detection and treatment improvement, and tumour biology. The cumulative results of the trial suggest that surrogate endpoints for disease-specific mortality should not currently be used in screening trials for ovarian cancer. National Institute for Health Research, Medical Research Council, Cancer Research UK, The Eve Appeal. [ABSTRACT FROM AUTHOR]
Published: 2023
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163. Serum biomarker-based early detection of pancreatic ductal adenocarcinomas with ensemble learning

Author: Nené, Nuno R., primary, Ney, Alexander, additional, Nazarenko, Tatiana, additional, Blyuss, Oleg, additional, Johnston, Harvey E., additional, Whitwell, Harry J., additional, Sedlak, Eva, additional, Gentry-Maharaj, Aleksandra, additional, Apostolidou, Sophia, additional, Costello, Eithne, additional, Greenhalf, William, additional, Jacobs, Ian, additional, Menon, Usha, additional, Hsuan, Justin, additional, Pereira, Stephen P., additional, Zaikin, Alexey, additional, and Timms, John F., additional
Published: 2023
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164. Why Did Downstaging in the United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) Not Result in a Mortality Benefit: Exploratory Analysis of a Randomised Controlled Trial

Author: Menon, Usha, primary, Gentry-Maharaj, Aleksandra, additional, Burnell, Matthew, additional, Ryan, Andy, additional, Singh, Naveena, additional, Manchanda, Ranjit, additional, Kalsi, Jatinderpal K., additional, Woolas, Robert, additional, Arora, Rupali, additional, Casey, Laura, additional, Dawnay, Anne, additional, Sharma, Aarti, additional, Williamson, Karin, additional, Apostolidou, Sophia, additional, Fallowfield, Lesley, additional, McGuire, Alistair, additional, Campbell, Stuart, additional, Skates, Steven J., additional, Jacobs, Ian J., additional, and Parmar, Mahesh KB, additional
Published: 2023
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165. Profiling the immune landscape in mucinous ovarian carcinoma

Author: Meagher, Nicola S., primary, Hamilton, Phineas, additional, Milne, Katy, additional, Thornton, Shelby, additional, Harris, Bronwyn, additional, Weir, Ashley, additional, Alsop, Jennifer, additional, Bisinoto, Christiani, additional, Brenton, James D., additional, Brooks-Wilson, Angela, additional, Chiu, Derek S., additional, Cushing-Haugen, Kara L., additional, Fereday, Sian, additional, Garsed, Dale W., additional, Gayther, Simon A., additional, Gentry-Maharaj, Aleksandra, additional, Gilks, Blake, additional, Jimenez-Linan, Mercedes, additional, Kennedy, Catherine J., additional, Le, Nhu D., additional, Piskorz, Anna M., additional, Riggan, Marjorie J., additional, Shah, Mitul, additional, Singh, Naveena, additional, Talhouk, Aline, additional, Widschwendter, Martin, additional, Bowtell, David D.L., additional, Candido dos Reis, Francisco J., additional, Cook, Linda S., additional, Fortner, Renée T., additional, García, María J., additional, Harris, Holly R., additional, Huntsman, David G., additional, Karnezis, Anthony N., additional, Köbel, Martin, additional, Menon, Usha, additional, Pharoah, Paul D.P., additional, Doherty, Jennifer A., additional, Anglesio, Michael S., additional, Pike, Malcolm C., additional, Pearce, Celeste Leigh, additional, Friedlander, Michael L., additional, DeFazio, Anna, additional, Nelson, Brad H., additional, and Ramus, Susan J., additional
Published: 2023
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166. Evaluating the ovarian cancer gonadotropin hypothesis: A candidate gene study

Author: Lee, Alice W., Tyrer, Jonathan P., Doherty, Jennifer A., Stram, Douglas A., Kupryjanczyk, Jolanta, Dansonka-Mieszkowska, Agnieszka, Plisiecka-Halasa, Joanna, Spiewankiewicz, Beata, Myers, Emily J., Chenevix-Trench, Georgia, Fasching, Peter A., Beckmann, Matthias W., Ekici, Arif B., Hein, Alexander, Vergote, Ignace, Van Nieuwenhuysen, Els, Lambrechts, Diether, Wicklund, Kristine G., Eilber, Ursula, Wang-Gohrke, Shan, Chang-Claude, Jenny, Rudolph, Anja, Sucheston-Campbell, Lara, Odunsi, Kunle, Moysich, Kirsten B., Shvetsov, Yurii B., Thompson, Pamela J., Goodman, Marc T., Wilkens, Lynne R., Dörk, Thilo, Hillemanns, Peter, Dürst, Matthias, Runnebaum, Ingo B., Bogdanova, Natalia, Pelttari, Liisa M., Nevanlinna, Heli, Leminen, Arto, Edwards, Robert P., Kelley, Joseph L., Harter, Philipp, Schwaab, Ira, Heitz, Florian, du Bois, Andreas, Orsulic, Sandra, Lester, Jenny, Walsh, Christine, Karlan, Beth Y., Hogdall, Estrid, Kjaer, Susanne K., Jensen, Allan, Vierkant, Robert A., Cunningham, Julie M., Goode, Ellen L., Fridley, Brooke L., Southey, Melissa C., Giles, Graham G., Bruinsma, Fiona, Wu, Xifeng, Hildebrandt, Michelle A.T., Lu, Karen, Liang, Dong, Bisogna, Maria, Levine, Douglas A., Weber, Rachel Palmieri, Schildkraut, Joellen M., Iversen, Edwin S., Berchuck, Andrew, Terry, Kathryn L., Cramer, Daniel W., Tworoger, Shelley S., Poole, Elizabeth M., Olson, Sara H., Orlow, Irene, Bandera, Elisa V., Bjorge, Line, Tangen, Ingvild L., Salvesen, Helga B., Krakstad, Camilla, Massuger, Leon F.A.G., Kiemeney, Lambertus A., Aben, Katja K.H., van Altena, Anne M., Bean, Yukie, Pejovic, Tanja, Kellar, Melissa, Le, Nhu D., Cook, Linda S., Kelemen, Linda E., Brooks-Wilson, Angela, Lubinski, Jan, Gronwald, Jacek, Cybulski, Cezary, Jakubowska, Anna, Wentzensen, Nicolas, Brinton, Louise A., Lissowska, Jolanta, Yang, Hannah, Nedergaard, Lotte, Lundvall, Lene, Hogdall, Claus, Song, Honglin, Campbell, Ian G., Eccles, Diana, Glasspool, Rosalind, Siddiqui, Nadeem, Carty, Karen, Paul, James, McNeish, Iain A., Sieh, Weiva, McGuire, Valerie, Rothstein, Joseph H., Whittemore, Alice S., McLaughlin, John R., Risch, Harvey A., Phelan, Catherine M., Anton-Culver, Hoda, Ziogas, Argyrios, Menon, Usha, Ramus, Susan J., Gentry-Maharaj, Aleksandra, Harrington, Patricia, Pike, Malcolm C., Modugno, Francesmary, Rossing, Mary Anne, Ness, Roberta B., Pharoah, Paul D.P., Stram, Daniel O., Wu, Anna H., and Pearce, Celeste Leigh
Published: 2015
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167. CCNE1 and survival of patients with tubo-ovarian high-grade serous carcinoma: An Ovarian Tumor Tissue Analysis consortium study

Author: Kang, Eun-Young, Weir, Ashley, Meagher, Nicola S, Farrington, Kyo, Nelson, Gregg S, Ghatage, Prafull, Lee, Cheng-Han, Riggan, Marjorie J, Bolithon, Adelyn, Popovic, Gordana, Leung, Betty, Tang, Katrina, Lambie, Neil, Millstein, Joshua, Alsop, Jennifer, Anglesio, Michael S, Ataseven, Beyhan, Barlow, Ellen, Beckmann, Matthias W, Berger, Jessica, Bisinotto, Christiani, Bösmüller, Hans, Boros, Jessica, Brand, Alison H, Brooks-Wilson, Angela, Brucker, Sara Y, Carney, Michael E, Casablanca, Yovanni, Cazorla-Jiménez, Alicia, Cohen, Paul A, Conrads, Thomas P, Cook, Linda S, Coulson, Penny, Courtney-Brooks, Madeleine, Cramer, Daniel W, Crowe, Philip, Cunningham, Julie M, Cybulski, Cezary, Darcy, Kathleen M, El-Bahrawy, Mona A, Elishaev, Esther, Erber, Ramona, Farrell, Rhonda, Fereday, Sian, Fischer, Anna, García, María J, Gayther, Simon A, Gentry-Maharaj, Aleksandra, Gilks, C Blake, AOCS Group, Grube, Marcel, Harnett, Paul R, Harrington, Shariska Petersen, Harter, Philipp, Hartmann, Arndt, Hecht, Jonathan L, Heikaus, Sebastian, Hein, Alexander, Heitz, Florian, Hendley, Joy, Hernandez, Brenda Y, Polo, Susanna Hernando, Heublein, Sabine, Hirasawa, Akira, Høgdall, Estrid, Høgdall, Claus K, Horlings, Hugo M, Huntsman, David G, Huzarski, Tomasz, Jewell, Andrea, Jimenez-Linan, Mercedes, Jones, Michael E, Kaufmann, Scott H, Kennedy, Catherine J, Khabele, Dineo, Kommoss, Felix KF, Kruitwagen, Roy FPM, Lambrechts, Diether, Le, Nhu D, Lener, Marcin, Lester, Jenny, Leung, Yee, Linder, Anna, Loverix, Liselore, Lubiński, Jan, Madan, Rashna, Maxwell, G Larry, Modugno, Francesmary, Neuhausen, Susan L, Olawaiye, Alexander, Olbrecht, Siel, Orsulic, Sandra, Palacios, José, Pearce, Celeste Leigh, Pike, Malcolm C, Quinn, Carmel M, Mohan, Ganendra Raj, Rodríguez-Antona, Cristina, Ruebner, Matthias, Ryan, Andy, Salfinger, Stuart G, Sasamoto, Naoko, Schildkraut, Joellen M, Schoemaker, Minouk J, Shah, Mitul, Sharma, Raghwa, Shvetsov, Yurii B, Singh, Naveena, Sonke, Gabe S, Steele, Linda, Stewart, Colin, Sundfeldt, Karin, Swerdlow, Anthony J, Talhouk, Aline, Tan, Adeline, Taylor, Sarah E, Terry, Kathryn L, Tołoczko, Aleksandra, Traficante, Nadia, Van De Vijver, Koen K, Van Der Aa, Maaike A, Van Gorp, Toon, Van Nieuwenhuysen, Els, Van-Wagensveld, Lilian, Vergote, Ignace, Vierkant, Robert A, Wang, Chen, Wilkens, Lynne R, Winham, Stacey J, Wu, Anna H, Benitez, Javier, Berchuck, Andrew, Candido Dos Reis, Francisco J, DeFazio, Anna, Fasching, Peter A, Goode, Ellen L, Goodman, Marc T, Gronwald, Jacek, Karlan, Beth Y, Kommoss, Stefan, Menon, Usha, Sinn, Hans-Peter, Staebler, Annette, Brenton, James D, Bowtell, David D, Pharoah, Paul DP, Ramus, Susan J, Köbel, Martin, Meagher, Nicola S [0000-0001-9134-2118], Lee, Cheng-Han [0000-0003-2094-1222], Fereday, Sian [0000-0002-8559-8579], Kennedy, Catherine J [0000-0002-4465-5784], Sasamoto, Naoko [0000-0002-4526-2181], Schildkraut, Joellen M [0000-0002-0990-9339], Talhouk, Aline [0000-0001-7760-410X], Vergote, Ignace [0000-0002-7589-8981], Köbel, Martin [0000-0002-6615-2037], and Apollo - University of Cambridge Repository
Subjects: Ovarian Neoplasms, Oncogene Proteins, Carcinoma, Cystadenocarcinoma, Serous, ovarian cancer, high-grade serous carcinoma, Cyclin E, Humans, Female, prognosis, RNA, Messenger, CCNE1 amplification, cyclin E1 expression, Transcription Factors
Abstract: BACKGROUND: Cyclin E1 (CCNE1) is a potential predictive marker and therapeutic target in tubo-ovarian high-grade serous carcinoma (HGSC). Smaller studies have revealed unfavorable associations for CCNE1 amplification and CCNE1 overexpression with survival, but to date no large-scale, histotype-specific validation has been performed. The hypothesis was that high-level amplification of CCNE1 and CCNE1 overexpression, as well as a combination of the two, are linked to shorter overall survival in HGSC. METHODS: Within the Ovarian Tumor Tissue Analysis consortium, amplification status and protein level in 3029 HGSC cases and mRNA expression in 2419 samples were investigated. RESULTS: High-level amplification (>8 copies by chromogenic in situ hybridization) was found in 8.6% of HGSC and overexpression (>60% with at least 5% demonstrating strong intensity by immunohistochemistry) was found in 22.4%. CCNE1 high-level amplification and overexpression both were linked to shorter overall survival in multivariate survival analysis adjusted for age and stage, with hazard stratification by study (hazard ratio [HR], 1.26; 95% CI, 1.08-1.47, p = .034, and HR, 1.18; 95% CI, 1.05-1.32, p = .015, respectively). This was also true for cases with combined high-level amplification/overexpression (HR, 1.26; 95% CI, 1.09-1.47, p = .033). CCNE1 mRNA expression was not associated with overall survival (HR, 1.00 per 1-SD increase; 95% CI, 0.94-1.06; p = .58). CCNE1 high-level amplification is mutually exclusive with the presence of germline BRCA1/2 pathogenic variants and shows an inverse association to RB1 loss. CONCLUSION: This study provides large-scale validation that CCNE1 high-level amplification is associated with shorter survival, supporting its utility as a prognostic biomarker in HGSC.
Published: 2023
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168. Identification of 12 new susceptibility loci for different histotypes of epithelial ovarian cancer

Author: Phelan, Catherine M, Kuchenbaecker, Karoline B, Tyrer, Jonathan P, Kar, Siddhartha P, Lawrenson, Kate, Winham, Stacey J, Dennis, Joe, Pirie, Ailith, Riggan, Marjorie J, Chornokur, Ganna, Earp, Madalene A, Lyra, Jr, Paulo C, Lee, Janet M, Coetzee, Simon, Beesley, Jonathan, McGuffog, Lesley, Soucy, Penny, Dicks, Ed, Lee, Andrew, Barrowdale, Daniel, Lecarpentier, Julie, Leslie, Goska, Aalfs, Cora M, Aben, Katja K H, Adams, Marcia, Adlard, Julian, Andrulis, Irene L, Anton-Culver, Hoda, Antonenkova, Natalia, Aravantinos, Gerasimos, Arnold, Norbert, Arun, Banu K, Arver, Brita, Azzollini, Jacopo, Balmaña, Judith, Banerjee, Susana N, Barjhoux, Laure, Barkardottir, Rosa B, Bean, Yukie, Beckmann, Matthias W, Beeghly-Fadiel, Alicia, Benitez, Javier, Bermisheva, Marina, Bernardini, Marcus Q, Birrer, Michael J, Bjorge, Line, Black, Amanda, Blankstein, Kenneth, Blok, Marinus J, Bodelon, Clara, Bogdanova, Natalia, Bojesen, Anders, Bonanni, Bernardo, Borg, Åke, Bradbury, Angela R, Brenton, James D, Brewer, Carole, Brinton, Louise, Broberg, Per, Brooks-Wilson, Angela, Bruinsma, Fiona, Brunet, Joan, Buecher, Bruno, Butzow, Ralf, Buys, Saundra S, Caldes, Trinidad, Caligo, Maria A, Campbell, Ian, Cannioto, Rikki, Carney, Michael E, Cescon, Terence, Chan, Salina B, Chang-Claude, Jenny, Chanock, Stephen, Chen, Xiao Qing, Chiew, Yoke-Eng, Chiquette, Jocelyne, Chung, Wendy K, Claes, Kathleen B M, Conner, Thomas, Cook, Linda S, Cook, Jackie, Cramer, Daniel W, Cunningham, Julie M, D'Aloisio, Aimee A, Daly, Mary B, Damiola, Francesca, Damirovna, Sakaeva Dina, Dansonka-Mieszkowska, Agnieszka, Dao, Fanny, Davidson, Rosemarie, DeFazio, Anna, Delnatte, Capucine, Doheny, Kimberly F, Diez, Orland, Ding, Yuan Chun, Doherty, Jennifer Anne, Domchek, Susan M, Dorfling, Cecilia M, Dörk, Thilo, Dossus, Laure, Duran, Mercedes, Dürst, Matthias, Dworniczak, Bernd, Eccles, Diana, Edwards, Todd, Eeles, Ros, Eilber, Ursula, Ejlertsen, Bent, Ekici, Arif B, Ellis, Steve, Elvira, Mingajeva, Eng, Kevin H, Engel, Christoph, Evans, D Gareth, Fasching, Peter A, Ferguson, Sarah, Ferrer, Sandra Fert, Flanagan, James M, Fogarty, Zachary C, Fortner, Renée T, Fostira, Florentia, Foulkes, William D, Fountzilas, George, Fridley, Brooke L, Friebel, Tara M, Friedman, Eitan, Frost, Debra, Ganz, Patricia A, Garber, Judy, García, María J, Garcia-Barberan, Vanesa, Gehrig, Andrea, Gentry-Maharaj, Aleksandra, Gerdes, Anne-Marie, Giles, Graham G, Glasspool, Rosalind, Glendon, Gord, Godwin, Andrew K, Goldgar, David E, Goranova, Teodora, Gore, Martin, Greene, Mark H, Gronwald, Jacek, Gruber, Stephen, Hahnen, Eric, Haiman, Christopher A, Håkansson, Niclas, Hamann, Ute, Hansen, Thomas V O, Harrington, Patricia A, Harris, Holly R, Hauke, Jan, Hein, Alexander, Henderson, Alex, Hildebrandt, Michelle A T, Hillemanns, Peter, Hodgson, Shirley, Høgdall, Claus K, Høgdall, Estrid, Hogervorst, Frans B L, Holland, Helene, Hooning, Maartje J, Hosking, Karen, Huang, Ruea-Yea, Hulick, Peter J, Hung, Jillian, Hunter, David J, Huntsman, David G, Huzarski, Tomasz, Imyanitov, Evgeny N, Isaacs, Claudine, Iversen, Edwin S, Izatt, Louise, Izquierdo, Angel, Jakubowska, Anna, James, Paul, Janavicius, Ramunas, Jernetz, Mats, Jensen, Allan, Jensen, Uffe Birk, John, Esther M, Johnatty, Sharon, Jones, Michael E, Kannisto, Päivi, Karlan, Beth Y, Karnezis, Anthony, Kast, Karin, Kennedy, Catherine J, Khusnutdinova, Elza, Kiemeney, Lambertus A, Kiiski, Johanna I, Kim, Sung-Won, Kjaer, Susanne K, Köbel, Martin, Kopperud, Reidun K, Kruse, Torben A, Kupryjanczyk, Jolanta, Kwong, Ava, Laitman, Yael, Lambrechts, Diether, Larrañaga, Nerea, Larson, Melissa C, Lazaro, Conxi, Le, Nhu D, Le Marchand, Loic, Lee, Jong Won, Lele, Shashikant B, Leminen, Arto, Leroux, Dominique, Lester, Jenny, Lesueur, Fabienne, Levine, Douglas A, Liang, Dong, Liebrich, Clemens, Lilyquist, Jenna, Lipworth, Loren, Lissowska, Jolanta, Lu, Karen H, Lubinński, Jan, Luccarini, Craig, Lundvall, Lene, Mai, Phuong L, Mendoza-Fandiño, Gustavo, Manoukian, Siranoush, Massuger, Leon F A G, May, Taymaa, Mazoyer, Sylvie, McAlpine, Jessica N, McGuire, Valerie, McLaughlin, John R, McNeish, Iain, Meijers-Heijboer, Hanne, Meindl, Alfons, Menon, Usha, Mensenkamp, Arjen R, Merritt, Melissa A, Milne, Roger L, Mitchell, Gillian, Modugno, Francesmary, Moes-Sosnowska, Joanna, Moffitt, Melissa, Montagna, Marco, Moysich, Kirsten B, Mulligan, Anna Marie, Musinsky, Jacob, Nathanson, Katherine L, Nedergaard, Lotte, Ness, Roberta B, Neuhausen, Susan L, Nevanlinna, Heli, Niederacher, Dieter, Nussbaum, Robert L, Odunsi, Kunle, Olah, Edith, Olopade, Olufunmilayo I, Olsson, Håkan, Olswold, Curtis, O'Malley, David M, Ong, Kai-ren, Onland-Moret, N Charlotte, Orr, Nicholas, Orsulic, Sandra, Osorio, Ana, Palli, Domenico, Papi, Laura, Park-Simon, Tjoung-Won, Paul, James, Pearce, Celeste L, Pedersen, Inge Søkilde, Peeters, Petra H M, Peissel, Bernard, Peixoto, Ana, Pejovic, Tanja, Pelttari, Liisa M, Permuth, Jennifer B, Peterlongo, Paolo, Pezzani, Lidia, Pfeiler, Georg, Phillips, Kelly-Anne, Piedmonte, Marion, Pike, Malcolm C, Piskorz, Anna M, Poblete, Samantha R, Pocza, Timea, Poole, Elizabeth M, Poppe, Bruce, Porteous, Mary E, Prieur, Fabienne, Prokofyeva, Darya, Pugh, Elizabeth, Pujana, Miquel Angel, Pujol, Pascal, Radice, Paolo, Rantala, Johanna, Rappaport-Fuerhauser, Christine, Rennert, Gad, Rhiem, Kerstin, Rice, Patricia, Richardson, Andrea, Robson, Mark, Rodriguez, Gustavo C, Rodríguez-Antona, Cristina, Romm, Jane, Rookus, Matti A, Rossing, Mary Anne, Rothstein, Joseph H, Rudolph, Anja, Runnebaum, Ingo B, Salvesen, Helga B, Sandler, Dale P, Schoemaker, Minouk J, Senter, Leigha, Setiawan, V Wendy, Severi, Gianluca, Sharma, Priyanka, Shelford, Tameka, Siddiqui, Nadeem, Side, Lucy E, Sieh, Weiva, Singer, Christian F, Sobol, Hagay, Song, Honglin, Southey, Melissa C, Spurdle, Amanda B, Stadler, Zsofia, Steinemann, Doris, Stoppa-Lyonnet, Dominique, Sucheston-Campbell, Lara E, Sukiennicki, Grzegorz, Sutphen, Rebecca, Sutter, Christian, Swerdlow, Anthony J, Szabo, Csilla I, Szafron, Lukasz, Tan, Yen Y, Taylor, Jack A, Tea, Muy-Kheng, Teixeira, Manuel R, Teo, Soo-Hwang, Terry, Kathryn L, Thompson, Pamela J, Thomsen, Liv Cecilie Vestrheim, Thull, Darcy L, Tihomirova, Laima, Tinker, Anna V, Tischkowitz, Marc, Tognazzo, Silvia, Toland, Amanda Ewart, Tone, Alicia, Trabert, Britton, Travis, Ruth C, Trichopoulou, Antonia, Tung, Nadine, Tworoger, Shelley S, van Altena, Anne M, Van Den Berg, David, van der Hout, Annemarie H, van der Luijt, Rob B, Van Heetvelde, Mattias, Van Nieuwenhuysen, Els, van Rensburg, Elizabeth J, Vanderstichele, Adriaan, Varon-Mateeva, Raymonda, Vega, Ana, Edwards, Digna Velez, Vergote, Ignace, Vierkant, Robert A, Vijai, Joseph, Vratimos, Athanassios, Walker, Lisa, Walsh, Christine, Wand, Dorothea, Wang-Gohrke, Shan, Wappenschmidt, Barbara, Webb, Penelope M, Weinberg, Clarice R, Weitzel, Jeffrey N, Wentzensen, Nicolas, Whittemore, Alice S, Wijnen, Juul T, Wilkens, Lynne R, Wolk, Alicja, Woo, Michelle, Wu, Xifeng, Wu, Anna H, Yang, Hannah, Yannoukakos, Drakoulis, Ziogas, Argyrios, Zorn, Kristin K, Narod, Steven A, Easton, Douglas F, Amos, Christopher I, Schildkraut, Joellen M, Ramus, Susan J, Ottini, Laura, Goodman, Marc T, Park, Sue K, Kelemen, Linda E, Risch, Harvey A, Thomassen, Mads, Offit, Kenneth, Simard, Jacques, Schmutzler, Rita Katharina, Hazelett, Dennis, Monteiro, Alvaro N, Couch, Fergus J, Berchuck, Andrew, Chenevix-Trench, Georgia, Goode, Ellen L, Sellers, Thomas A, Gayther, Simon A, Antoniou, Antonis C, and Pharoah, Paul D P
Published: 2017
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169. Multiprobabilistic Venn Predictors with Logistic Regression

Author: Nouretdinov, Ilia, Devetyarov, Dmitry, Burford, Brian, Camuzeaux, Stephane, Gentry-Maharaj, Aleksandra, Tiss, Ali, Smith, Celia, Luo, Zhiyuan, Chervonenkis, Alexey, Hallett, Rachel, Vovk, Volodya, Waterfield, Mike, Cramer, Rainer, Timms, John F., Jacobs, Ian, Menon, Usha, Gammerman, Alexander, Iliadis, Lazaros, editor, Maglogiannis, Ilias, editor, Papadopoulos, Harris, editor, Karatzas, Kostas, editor, and Sioutas, Spyros, editor
Published: 2012
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170. Ovarian cancer screening—Current status, future directions

Author: Menon, Usha, Griffin, Michelle, and Gentry-Maharaj, Aleksandra
Published: 2014
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171. Ovarian Cancer Prevention and Screening

Author: Menon, Usha, Karpinskyj, Chloe, and Gentry-Maharaj, Aleksandra
Published: 2018
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172. Robust Tests for Additive Gene-Environment Interaction in Case-Control Studies Using Gene-Environment Independence

Author: Liu, Gang, Mukherjee, Bhramar, Lee, Seunggeun, Lee, Alice W, Wu, Anna H, Bandera, Elisa V, Jensen, Allan, Rossing, Mary Anne, Moysich, Kirsten B, Chang-Claude, Jenny, Doherty, Jennifer A, Gentry-Maharaj, Aleksandra, Kiemeney, Lambertus, Gayther, Simon A, Modugno, Francesmary, Massuger, Leon, Goode, Ellen L, Fridley, Brooke L, Terry, Kathryn L, Cramer, Daniel W, Ramus, Susan J, Anton-Culver, Hoda, Ziogas, Argyrios, Tyrer, Jonathan P, Schildkraut, Joellen M, Kjaer, Susanne K, Webb, Penelope M, Ness, Roberta B, Menon, Usha, Berchuck, Andrew, Pharoah, Paul D, Risch, Harvey, and Pearce, Celeste Leigh
Published: 2018
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173. Metabolic Profiling of Adiponectin Levels in Adults: Mendelian Randomization Analysis

Author: Borges, Maria Carolina, Barros, Aluísio J.D., Ferreira, Diana L. Santos, Casas, Juan Pablo, Horta, Bernardo Lessa, Kivimaki, Mika, Kumari, Meena, Menon, Usha, Gaunt, Tom R., Ben-Shlomo, Yoav, Freitas, Deise F., Oliveira, Isabel O., Gentry-Maharaj, Aleksandra, Fourkala, Evangelia, Lawlor, Debbie A., and Hingorani, Aroon D.
Published: 2017
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174. Discovery and validation of serum glycoprotein biomarkers for high grade serous ovarian cancer.

Author: Dutt, Mriga, Hartel, Gunter, Richards, Renee S., Shah, Alok K., Mohamed, Ahmed, Apostolidou, Sophia, Gentry‐Maharaj, Aleksandra, Hooper, John D., Perrin, Lewis C., Menon, Usha, and Hill, Michelle M.
Published: 2023
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175. Hormone-receptor expression and ovarian cancer survival: an Ovarian Tumor Tissue Analysis consortium study

Author: Sieh, Weiva, Köbel, Martin, Longacre, Teri A, Bowtell, David D, deFazio, Anna, Goodman, Marc T, Høgdall, Estrid, Deen, Suha, Wentzensen, Nicolas, Moysich, Kirsten B, Brenton, James D, Clarke, Blaise A, Menon, Usha, Gilks, C Blake, Kim, Andre, Madore, Jason, Fereday, Sian, George, Joshy, Galletta, Laura, Lurie, Galina, Wilkens, Lynne R, Carney, Michael E, Thompson, Pamela J, Matsuno, Rayna K, Kjær, Susanne Krüger, Jensen, Allan, Høgdall, Claus, Kalli, Kimberly R, Fridley, Brooke L, Keeney, Gary L, Vierkant, Robert A, Cunningham, Julie M, Brinton, Louise A, Yang, Hannah P, Sherman, Mark E, García-Closas, Montserrat, Lissowska, Jolanta, Odunsi, Kunle, Morrison, Carl, Lele, Shashikant, Bshara, Wiam, Sucheston, Lara, Jimenez-Linan, Mercedes, Driver, Kristy, Alsop, Jennifer, Mack, Marie, McGuire, Valerie, Rothstein, Joseph H, Rosen, Barry P, Bernardini, Marcus Q, Mackay, Helen, Oza, Amit, Wozniak, Eva L, Benjamin, Elizabeth, Gentry-Maharaj, Aleksandra, Gayther, Simon A, Tinker, Anna V, Prentice, Leah M, Chow, Christine, Anglesio, Michael S, Johnatty, Sharon E, Chenevix-Trench, Georgia, Whittemore, Alice S, Pharoah, Paul DP, Goode, Ellen L, Huntsman, David G, and Ramus, Susan J
Published: 2013
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176. Cigarette smoking and risk of ovarian cancer: a pooled analysis of 21 case–control studies

Author: The Australian Cancer Study (Ovarian Cancer), Australian Ovarian Cancer Study Group, On behalf of the Ovarian Cancer Association Consortium, Faber, Mette T., Kjær, Susanne K., Dehlendorff, Christian, Chang-Claude, Jenny, Andersen, Klaus K., Høgdall, Estrid, Webb, Penelope M., Jordan, Susan J., Rossing, Mary Anne, Doherty, Jennifer A., Lurie, Galina, Thompson, Pamela J., Carney, Michael E., Goodman, Marc T., Ness, Roberta B., Modugno, Francesmary, Edwards, Robert P., Bunker, Clareann H., Goode, Ellen L., Fridley, Brooke L., Vierkant, Robert A., Larson, Melissa C., Schildkraut, Joellen, Cramer, Daniel W., Terry, Kathryn L., Vitonis, Allison F., Bandera, Elisa V., Olson, Sara H., King, Melony, Chandran, Urmila, Kiemeney, Lambertus A., Massuger, Leon F. A. G., van Altena, Anne M., Vermeulen, Sita H., Brinton, Louise, Wentzensen, Nicolas, Lissowska, Jolanta, Yang, Hannah P., Moysich, Kirsten B., Odunsi, Kunle, Kasza, Karin, Odunsi-Akanji, Oluwatosin, Song, Honglin, Pharaoh, Paul, Shah, Mitul, Whittemore, Alice S., McGuire, Valerie, Sieh, Weiva, Sutphen, Rebecca, Menon, Usha, Gayther, Simon A., Ramus, Susan J., Gentry-Maharaj, Aleksandra, Pearce, Celeste Leigh, Wu, Anna H., Pike, Malcolm C., Risch, Harvey A., and Jensen, Allan
Published: 2013

177. High Prediagnosis Inflammation-Related Risk Score Associated with Decreased Ovarian Cancer Survival.

Author: Brieger, Katharine K, Brieger, Katharine K, Phung, Minh Tung, Mukherjee, Bhramar, Bakulski, Kelly M, Anton-Culver, Hoda, Bandera, Elisa V, Bowtell, David DL, Cramer, Daniel W, DeFazio, Anna, Doherty, Jennifer A, Fereday, Sian, Fortner, Renée Turzanski, Gentry-Maharaj, Aleksandra, Goode, Ellen L, Goodman, Marc T, Harris, Holly R, Matsuo, Keitaro, Menon, Usha, Modugno, Francesmary, Moysich, Kirsten B, Qin, Bo, Ramus, Susan J, Risch, Harvey A, Rossing, Mary Anne, Schildkraut, Joellen M, Trabert, Britton, Vierkant, Robert A, Winham, Stacey J, Wentzensen, Nicolas, Wu, Anna H, Ziogas, Argyrios, Khoja, Lilah, Cho, Kathleen R, McLean, Karen, Richardson, Jean, Grout, Bronwyn, Chase, Anne, Deurloo, Cindy McKinnon, Odunsi, Kunle, Nelson, Brad H, Brenton, James D, Terry, Kathryn L, Pharoah, Paul DP, Berchuck, Andrew, Hanley, Gillian E, Webb, Penelope M, Pike, Malcolm C, Pearce, Celeste Leigh, Ovarian Cancer Association Consortium, Brieger, Katharine K, Brieger, Katharine K, Phung, Minh Tung, Mukherjee, Bhramar, Bakulski, Kelly M, Anton-Culver, Hoda, Bandera, Elisa V, Bowtell, David DL, Cramer, Daniel W, DeFazio, Anna, Doherty, Jennifer A, Fereday, Sian, Fortner, Renée Turzanski, Gentry-Maharaj, Aleksandra, Goode, Ellen L, Goodman, Marc T, Harris, Holly R, Matsuo, Keitaro, Menon, Usha, Modugno, Francesmary, Moysich, Kirsten B, Qin, Bo, Ramus, Susan J, Risch, Harvey A, Rossing, Mary Anne, Schildkraut, Joellen M, Trabert, Britton, Vierkant, Robert A, Winham, Stacey J, Wentzensen, Nicolas, Wu, Anna H, Ziogas, Argyrios, Khoja, Lilah, Cho, Kathleen R, McLean, Karen, Richardson, Jean, Grout, Bronwyn, Chase, Anne, Deurloo, Cindy McKinnon, Odunsi, Kunle, Nelson, Brad H, Brenton, James D, Terry, Kathryn L, Pharoah, Paul DP, Berchuck, Andrew, Hanley, Gillian E, Webb, Penelope M, Pike, Malcolm C, Pearce, Celeste Leigh, and Ovarian Cancer Association Consortium
Abstract: BackgroundThere is suggestive evidence that inflammation is related to ovarian cancer survival. However, more research is needed to identify inflammation-related factors that are associated with ovarian cancer survival and to determine their combined effects.MethodsThis analysis used pooled data on 8,147 women with invasive epithelial ovarian cancer from the Ovarian Cancer Association Consortium. The prediagnosis inflammation-related exposures of interest included alcohol use; aspirin use; other nonsteroidal anti-inflammatory drug use; body mass index; environmental tobacco smoke exposure; history of pelvic inflammatory disease, polycystic ovarian syndrome, and endometriosis; menopausal hormone therapy use; physical inactivity; smoking status; and talc use. Using Cox proportional hazards models, the relationship between each exposure and survival was assessed in 50% of the data. A weighted inflammation-related risk score (IRRS) was developed, and its association with survival was assessed using Cox proportional hazards models in the remaining 50% of the data.ResultsThere was a statistically significant trend of increasing risk of death per quartile of the IRRS [HR = 1.09; 95% confidence interval (CI), 1.03-1.14]. Women in the upper quartile of the IRRS had a 31% higher death rate compared with the lowest quartile (95% CI, 1.11-1.54).ConclusionsA higher prediagnosis IRRS was associated with an increased mortality risk after an ovarian cancer diagnosis. Further investigation is warranted to evaluate whether postdiagnosis exposures are also associated with survival.ImpactGiven that pre- and postdiagnosis exposures are often correlated and many are modifiable, our study results can ultimately motivate the development of behavioral recommendations to enhance survival among patients with ovarian cancer.
Published: 2022

178. Appraising the role of previously reported risk factors in epithelial ovarian cancer risk: A Mendelian randomization analysis

Author: Yarmolinsky, James, Relton, Caroline L., Lophatananon, Artitaya, Muir, Kenneth, Menon, Usha, Gentry-Maharaj, Aleksandra, Walther, Axel, Zheng, Jie, Fasching, Peter, Zheng, Wei, Yin Ling, Woo, Park, Sue K., Kim, Byoung-Gie, Choi, Ji-Yeob, Park, Boyoung, Davey Smith, George, Martin, Richard M., and Lewis, Sarah J.
Subjects: Single nucleotide polymorphisms -- Research, Ovarian cancer -- Genetic aspects -- Risk factors, Carcinogenesis, Cancer research, Genetics, Hormones, Polycystic ovary syndrome, Carcinoma, Chromosomes, Medical research, Type 2 diabetes, Genomics, Legal liability, Genetic polymorphisms, Epidemiology, Menopause, Tumors, Endometriosis, Proxy, Genetic research, Hormone replacement therapy, Oral contraceptives, Novels, Biological sciences
Abstract: Background Various risk factors have been associated with epithelial ovarian cancer risk in observational epidemiological studies. However, the causal nature of the risk factors reported, and thus their suitability as effective intervention targets, is unclear given the susceptibility of conventional observational designs to residual confounding and reverse causation. Mendelian randomization (MR) uses genetic variants as proxies for risk factors to strengthen causal inference in observational studies. We used MR to evaluate the association of 12 previously reported risk factors (reproductive, anthropometric, clinical, lifestyle, and molecular factors) with risk of invasive epithelial ovarian cancer, invasive epithelial ovarian cancer histotypes, and low malignant potential tumours. Methods and findings Genetic instruments to proxy 12 risk factors were constructed by identifying single nucleotide polymorphisms (SNPs) that were robustly (P < 5 x 10.sup.-8) and independently associated with each respective risk factor in previously reported genome-wide association studies. These risk factors included genetic liability to 3 factors (endometriosis, polycystic ovary syndrome, type 2 diabetes) scaled to reflect a 50% higher odds liability to disease. We obtained summary statistics for the association of these SNPs with risk of overall and histotype-specific invasive epithelial ovarian cancer (22,406 cases; 40,941 controls) and low malignant potential tumours (3,103 cases; 40,941 controls) from the Ovarian Cancer Association Consortium (OCAC). The OCAC dataset comprises 63 genotyping project/case-control sets with participants of European ancestry recruited from 14 countries (US, Australia, Belarus, Germany, Belgium, Denmark, Finland, Norway, Canada, Poland, UK, Spain, Netherlands, and Sweden). SNPs were combined into multi-allelic inverse-variance-weighted fixed or random effects models to generate effect estimates and 95% confidence intervals (CIs). Three complementary sensitivity analyses were performed to examine violations of MR assumptions: MR-Egger regression and weighted median and mode estimators. A Bonferroni-corrected P value threshold was used to establish strong evidence (P < 0.0042) and suggestive evidence (0.0042 < P < 0.05) for associations. In MR analyses, there was strong or suggestive evidence that 2 of the 12 risk factors were associated with invasive epithelial ovarian cancer and 8 of the 12 were associated with 1 or more invasive epithelial ovarian cancer histotypes. There was strong evidence that genetic liability to endometriosis was associated with an increased risk of invasive epithelial ovarian cancer (odds ratio [OR] per 50% higher odds liability: 1.10, 95% CI 1.06-1.15; P = 6.94 x 10.sup.-7) and suggestive evidence that lifetime smoking exposure was associated with an increased risk of invasive epithelial ovarian cancer (OR per unit increase in smoking score: 1.36, 95% CI 1.04-1.78; P = 0.02). In analyses examining histotypes and low malignant potential tumours, the strongest associations found were between height and clear cell carcinoma (OR per SD increase: 1.36, 95% CI 1.15-1.61; P = 0.0003); age at natural menopause and endometrioid carcinoma (OR per year later onset: 1.09, 95% CI 1.02-1.16; P = 0.007); and genetic liability to polycystic ovary syndrome and endometrioid carcinoma (OR per 50% higher odds liability: 0.89, 95% CI 0.82-0.96; P = 0.002). There was little evidence for an association of genetic liability to type 2 diabetes, parity, or circulating levels of 25-hydroxyvitamin D and sex hormone binding globulin with ovarian cancer or its subtypes. The primary limitations of this analysis include the modest statistical power for analyses of risk factors in relation to some less common ovarian cancer histotypes (low grade serous, mucinous, and clear cell carcinomas), the inability to directly examine the association of some ovarian cancer risk factors that did not have robust genetic variants available to serve as proxies (e.g., oral contraceptive use, hormone replacement therapy), and the assumption of linear relationships between risk factors and ovarian cancer risk. Conclusions Our comprehensive examination of possible aetiological drivers of ovarian carcinogenesis using germline genetic variants to proxy risk factors supports a role for few of these factors in invasive epithelial ovarian cancer overall and suggests distinct aetiologies across histotypes. The identification of novel risk factors remains an important priority for the prevention of epithelial ovarian cancer., Author(s): James Yarmolinsky 1,2, Caroline L. Relton 1,2,3, Artitaya Lophatananon 4, Kenneth Muir 4, Usha Menon 5, Aleksandra Gentry-Maharaj 5, Axel Walther 6, Jie Zheng 1,2, Peter Fasching 7, Wei [...]
Published: 2019
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179. Lifetime ovulatory years and risk of epithelial ovarian cancer: a multinational pooled analysis.

Author: Fu, Zhuxuan, Brooks, Maria Mori, Irvin, Sarah, Jordan, Susan, Aben, Katja K H, Anton-Culver, Hoda, Bandera, Elisa V, Beckmann, Matthias W, Berchuck, Andrew, Brooks-Wilson, Angela, Chang-Claude, Jenny, Cook, Linda S, Cramer, Daniel W, Cushing-Haugen, Kara L, Doherty, Jennifer A, Ekici, Arif B, Fasching, Peter A, Fortner, Renée T, Gayther, Simon A, and Gentry-Maharaj, Aleksandra
Subjects: CONTRACEPTION, OVARIAN epithelial cancer, ORAL contraceptives, BETA (Finance), OVULATION, ANOVULATION
Abstract: Background The role of ovulation in epithelial ovarian cancer (EOC) is supported by the consistent protective effects of parity and oral contraceptive use. Whether these factors protect through anovulation alone remains unclear. We explored the association between lifetime ovulatory years (LOY) and EOC. Methods LOY was calculated using 12 algorithms. Odds ratios (ORs) and 95% confidence intervals (CIs) estimated the association between LOY or LOY components and EOC among 26 204 control participants and 21 267 case patients from 25 studies. To assess whether LOY components act through ovulation suppression alone, we compared beta coefficients obtained from regression models with expected estimates assuming 1 year of ovulation suppression has the same effect regardless of source. Results LOY was associated with increased EOC risk (OR per year increase = 1.014, 95% CI = 1.009 to 1.020 to OR per year increase = 1.044, 95% CI = 1.041 to 1.048). Individual LOY components, except age at menarche, also associated with EOC. The estimated model coefficient for oral contraceptive use and pregnancies were 4.45 times and 12- to 15-fold greater than expected, respectively. LOY was associated with high-grade serous, low-grade serous, endometrioid, and clear cell histotypes (ORs per year increase = 1.054, 1.040, 1.065, and 1.098, respectively) but not mucinous tumors. Estimated coefficients of LOY components were close to expected estimates for high-grade serous but larger than expected for low-grade serous, endometrioid, and clear cell histotypes. Conclusions LOY is positively associated with nonmucinous EOC. Differences between estimated and expected model coefficients for LOY components suggest factors beyond ovulation underlie the associations between LOY components and EOC in general and for non-HGSOC. [ABSTRACT FROM AUTHOR]
Published: 2023
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180. Multiprobabilistic prediction in early medical diagnoses

Author: Nouretdinov, Ilia, Devetyarov, Dmitry, Vovk, Volodya, Burford, Brian, Camuzeaux, Stephane, Gentry-Maharaj, Aleksandra, Tiss, Ali, Smith, Celia, Luo, Zhiyuan, Chervonenkis, Alexey, Hallett, Rachel, Waterfield, Mike, Cramer, Rainer, Timms, John F., Jacobs, Ian, Menon, Usha, and Gammerman, Alex
Published: 2015
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181. Screening for ovarian cancer in the general population

Author: Gentry-Maharaj, Aleksandra and Menon, Usha
Published: 2012
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182. Dose-Response Association of CD8+ Tumor-Infiltrating Lymphocytes and Survival Time in High-Grade Serous Ovarian Cancer

Author: Goode, Ellen L., Block, Matthew S., Kalli, Kimberly R., Vierkant, Robert A., Chen, Wenqian, Fogarty, Zachary C., Gentry-Maharaj, Aleksandra, Tołoczko, Aleksandra, Hein, Alexander, Bouligny, Aliecia L., Jensen, Allan, Osorio, Ana, Hartkopf, Andreas D., Ryan, Andy, Chudecka-Głaz, Anita, Magliocco, Anthony M., Hartmann, Arndt, Jung, Audrey Y, Gao, Bo, Hernandez, Brenda Y., Fridley, Brooke L., McCauley, Bryan M., Kennedy, Catherine J., Wang, Chen, Karpinskyj, Chloe, de Sousa, Christiani B., Tiezzi, Daniel G., Wachter, David L., Herpel, Esther, Taran, Florin Andrei, Modugno, Francesmary, Nelson, Gregg, Lubiński, Jan, Menkiszak, Janusz, Alsop, Jennifer, Lester, Jenny, García-Donas, Jesús, Nation, Jill, Hung, Jillian, Palacios, José, Rothstein, Joseph H., Kelley, Joseph L., de Andrade, Jurandyr M., Robles-Díaz, Luis, Intermaggio, Maria P., Widschwendter, Martin, Beckmann, Matthias W., Ruebner, Matthias, Jimenez-Linan, Mercedes, Singh, Naveena, Oszurek, Oleg, Harnett, Paul R., Rambau, Peter F., Sinn, Peter, Wagner, Philipp, Ghatage, Prafull, Sharma, Raghwa, Edwards, Robert P., Ness, Roberta B., Orsulic, Sandra, Brucker, Sara Y., Johnatty, Sharon E., Longacre, Teri A., Eilber, Ursula, McGuire, Valerie, Sieh, Weiva, Natanzon, Yanina, Li, Zheng, Whittemore, Alice S., deFazio, Anna, Staebler, Annette, Karlan, Beth Y., Gilks, Blake, Bowtell, David D., Høgdall, Estrid, Candido dos Reis, Francisco J., Steed, Helen, Campbell, Ian G., Gronwald, Jacek, Benítez, Javier, Koziak, Jennifer M., Chang-Claude, Jenny, Moysich, Kirsten B., Kelemen, Linda E., Cook, Linda S., Goodman, Marc T., García, María José, Fasching, Peter A., Kommoss, Stefan, Deen, Suha, Kjaer, Susanne K., Menon, Usha, Brenton, James D., Pharoah, Paul D. P., Chenevix-Trench, Georgia, Huntsman, David G., Winham, Stacey J., Köbel, Martin, and Ramus, Susan J.
Published: 2017
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183. Recruitment to Multicentre Trials: Lessons from UKCTOCS: Descriptive Study

Author: Menon, Usha, Gentry-Maharaj, Aleksandra, Ryan, Andy, Sharma, Aarti, Burnell, Matthew, Hallett, Rachel, Lewis, Sara, Lopez, Alberto, Godfrey, Keith, Oram, David, Herod, Jonathan, Williamson, Karin, Seif, Mourad, Scott, Ian, Mould, Tim, Woolas, Robert, Murdoch, John, Dobbs, Stephen, Amso, Nazar, Leeson, Simon, Cruickshank, Derek, McGuire, Ali, Campbell, Stuart, Fallowfield, Lesley, Skates, Steve, Parmar, Mahesh, and Jacobs, Ian
Published: 2008
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184. Recruitment of newly diagnosed ovarian cancer patients proved challenging in a multicentre biobanking study

Author: Balogun, Nyaladzi, Gentry-Maharaj, Aleksandra, Wozniak, Eva L., Lim, Anita, Ryan, Andy, Ramus, Susan J., Ford, Jeremy, Burnell, Matthew, Widschwendter, Martin, Gessler, Sue F., Gayther, Simon A., Jacobs, Ian J., and Menon, Usha
Published: 2011
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185. Sensitivity of transvaginal ultrasound screening for endometrial cancer in postmenopausal women: a case-control study within the UKCTOCS cohort

Author: Jacobs, Ian, Gentry-Maharaj, Aleksandra, Burnell, Matthew, Manchanda, Ranjit, Singh, Naveena, Sharma, Aarti, Ryan, Andy, Seif, Mourad W, Amso, Nazar N, Turner, Gillian, Brunell, Carol, Fletcher, Gwendolen, Rangar, Rani, Ford, Kathy, Godfrey, Keith, Lopes, Alberto, Oram, David, Herod, Jonathan, Williamson, Karin, Scott, Ian, Jenkins, Howard, Mould, Tim, Woolas, Robert, Murdoch, John, Dobbs, Stephen, Leeson, Simon, Cruickshank, Derek, Skates, Steven J, Fallowfield, Lesley, Parmar, Mahesh, Campbell, Stuart, and Menon, Usha
Published: 2011
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186. Validated biomarker assays confirm that ARID1A loss is confounded with MMR deficiency, CD8+ TIL infiltration, and provides no independent prognostic value in endometriosis‐associated ovarian carcinomas

Author: Heinze, Karolin, primary, Nazeran, Tayyebeh M, additional, Lee, Sandra, additional, Krämer, Pauline, additional, Cairns, Evan S, additional, Chiu, Derek S, additional, Leung, Samuel CY, additional, Kang, Eun Young, additional, Meagher, Nicola S, additional, Kennedy, Catherine J, additional, Boros, Jessica, additional, Kommoss, Friedrich, additional, Vollert, Hans‐Walter, additional, Heitz, Florian, additional, du Bois, Andreas, additional, Harter, Philipp, additional, Grube, Marcel, additional, Kraemer, Bernhard, additional, Staebler, Annette, additional, Kommoss, Felix KF, additional, Heublein, Sabine, additional, Sinn, Hans‐Peter, additional, Singh, Naveena, additional, Laslavic, Angela, additional, Elishaev, Esther, additional, Olawaiye, Alex, additional, Moysich, Kirsten, additional, Modugno, Francesmary, additional, Sharma, Raghwa, additional, Brand, Alison H, additional, Harnett, Paul R, additional, DeFazio, Anna, additional, Fortner, Renée T, additional, Lubinski, Jan, additional, Lener, Marcin, additional, Tołoczko‐Grabarek, Aleksandra, additional, Cybulski, Cezary, additional, Gronwald, Helena, additional, Gronwald, Jacek, additional, Coulson, Penny, additional, El‐Bahrawy, Mona A, additional, Jones, Michael E, additional, Schoemaker, Minouk J, additional, Swerdlow, Anthony J, additional, Gorringe, Kylie L, additional, Campbell, Ian, additional, Cook, Linda, additional, Gayther, Simon A, additional, Carney, Michael E, additional, Shvetsov, Yurii B, additional, Hernandez, Brenda Y, additional, Wilkens, Lynne R, additional, Goodman, Marc T, additional, Mateoiu, Constantina, additional, Linder, Anna, additional, Sundfeldt, Karin, additional, Kelemen, Linda E, additional, Gentry‐Maharaj, Aleksandra, additional, Widschwendter, Martin, additional, Menon, Usha, additional, Bolton, Kelly L, additional, Alsop, Jennifer, additional, Shah, Mitul, additional, Jimenez‐Linan, Mercedes, additional, Pharoah, Paul DP, additional, Brenton, James D, additional, Cushing‐Haugen, Kara L, additional, Harris, Holly R, additional, Doherty, Jennifer A, additional, Gilks, Blake, additional, Ghatage, Prafull, additional, Huntsman, David G, additional, Nelson, Gregg S, additional, Tinker, Anna V, additional, Lee, Cheng‐Han, additional, Goode, Ellen L, additional, Nelson, Brad H, additional, Ramus, Susan J, additional, Kommoss, Stefan, additional, Talhouk, Aline, additional, Köbel, Martin, additional, and Anglesio, Michael S, additional
Published: 2022
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187. High Prediagnosis Inflammation-Related Risk Score Associated with Decreased Ovarian Cancer Survival

Author: Brieger, Katharine K., primary, Phung, Minh Tung, additional, Mukherjee, Bhramar, additional, Bakulski, Kelly M., additional, Anton-Culver, Hoda, additional, Bandera, Elisa V., additional, Bowtell, David D.L., additional, Cramer, Daniel W., additional, DeFazio, Anna, additional, Doherty, Jennifer A., additional, Fereday, Sian, additional, Fortner, Renée Turzanski, additional, Gentry-Maharaj, Aleksandra, additional, Goode, Ellen L., additional, Goodman, Marc T., additional, Harris, Holly R., additional, Matsuo, Keitaro, additional, Menon, Usha, additional, Modugno, Francesmary, additional, Moysich, Kirsten B., additional, Qin, Bo, additional, Ramus, Susan J., additional, Risch, Harvey A., additional, Rossing, Mary Anne, additional, Schildkraut, Joellen M., additional, Trabert, Britton, additional, Vierkant, Robert A., additional, Winham, Stacey J., additional, Wentzensen, Nicolas, additional, Wu, Anna H., additional, Ziogas, Argyrios, additional, Khoja, Lilah, additional, Cho, Kathleen R., additional, McLean, Karen, additional, Richardson, Jean, additional, Grout, Bronwyn, additional, Chase, Anne, additional, Deurloo, Cindy McKinnon, additional, Odunsi, Kunle, additional, Nelson, Brad H., additional, Brenton, James D., additional, Terry, Kathryn L., additional, Pharoah, Paul D.P., additional, Berchuck, Andrew, additional, Hanley, Gillian E., additional, Webb, Penelope M., additional, Pike, Malcolm C., additional, and Pearce, Celeste Leigh, additional
Published: 2022
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188. Early detection of pancreatic ductal adenocarcinomas with an ensemble learning model based on a panel of protein serum biomarkers

Author: Nene, Nuno Rocha, primary, Ney, Alexander, additional, Nazarenko, Tatiana, additional, Blyuss, Oleg, additional, Johnston, Harvey, additional, Whitwell, Harry, additional, Sedlak, Eva, additional, Gentry-Maharaj, Aleksandra, additional, Costello, Eithne, additional, Greenhalf, William, additional, Jacobs, Ian, additional, Menon, Usha, additional, Hsuan, Justin, additional, Pereira, Stephen, additional, Zaikin, Alexey, additional, and Timms, John, additional
Published: 2021
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189. Genome-wide association study of subtype-specific epithelial ovarian cancer risk alleles using pooled DNA

Author: Earp, Madalene A., Kelemen, Linda E., Magliocco, Anthony M., Swenerton, Kenneth D., Chenevix-Trench, Georgia, Lu, Yi, Hein, Alexander, Ekici, Arif B., Beckmann, Matthias W., Fasching, Peter A., Lambrechts, Diether, Despierre, Evelyn, Vergote, Ignace, Lambrechts, Sandrina, Doherty, Jennifer A., Rossing, Mary Anne, Chang-Claude, Jenny, Rudolph, Anja, Friel, Grace, Moysich, Kirsten B., Odunsi, Kunle, Sucheston-Campbell, Lara, Lurie, Galina, Goodman, Marc T., Carney, Michael E., Thompson, Pamela J., Runnebaum, Ingo B., Dürst, Matthias, Hillemanns, Peter, Dörk, Thilo, Antonenkova, Natalia, Bogdanova, Natalia, Leminen, Arto, Nevanlinna, Heli, Pelttari, Liisa M., Butzow, Ralf, Bunker, Clareann H., Modugno, Francesmary, Edwards, Robert P., Ness, Roberta B., du Bois, Andreas, Heitz, Florian, Schwaab, Ira, Harter, Philipp, Karlan, Beth Y., Walsh, Christine, Lester, Jenny, Jensen, Allan, Kjær, Susanne K., Høgdall, Claus K., Høgdall, Estrid, Lundvall, Lene, Sellers, Thomas A., Fridley, Brooke L., Goode, Ellen L., Cunningham, Julie M., Vierkant, Robert A., Giles, Graham G., Baglietto, Laura, Severi, Gianluca, Southey, Melissa C., Liang, Dong, Wu, Xifeng, Lu, Karen, Hildebrandt, Michelle A. T., Levine, Douglas A., Bisogna, Maria, Schildkraut, Joellen M., Iversen, Edwin S., Weber, Rachel Palmieri, Berchuck, Andrew, Cramer, Daniel W., Terry, Kathryn L., Poole, Elizabeth M., Tworoger, Shelley S., Bandera, Elisa V., Chandran, Urmila, Orlow, Irene, Olson, Sara H., Wik, Elisabeth, Salvesen, Helga B., Bjorge, Line, Halle, Mari K., van Altena, Anne M., Aben, Katja K. H., Kiemeney, Lambertus A., Massuger, Leon F. A. G., Pejovic, Tanja, Bean, Yukie T., Cybulski, Cezary, Gronwald, Jacek, Lubinski, Jan, Wentzensen, Nicolas, Brinton, Louise A., Lissowska, Jolanta, Garcia-Closas, Montserrat, Dicks, Ed, Dennis, Joe, Easton, Douglas F., Song, Honglin, Tyrer, Jonathan P., Pharoah, Paul D. P., Eccles, Diana, Campbell, Ian G., Whittemore, Alice S., McGuire, Valerie, Sieh, Weiva, Rothstein, Joseph H., Flanagan, James M., Paul, James, Brown, Robert, Phelan, Catherine M., Risch, Harvey A., McLaughlin, John R., Narod, Steven A., Ziogas, Argyrios, Anton-Culver, Hoda, Gentry-Maharaj, Aleksandra, Menon, Usha, Gayther, Simon A., Ramus, Susan J., Wu, Anna H., Pearce, Celeste L., Pike, Malcolm C., Dansonka-Mieszkowska, Agnieszka, Rzepecka, Iwona K., Szafron, Lukasz M., Kupryjanczyk, Jolanta, Cook, Linda S., Le, Nhu D., Brooks-Wilson, Angela, Australian Cancer Study, Australian Ovarian Cancer Study Group, and On behalf of the Ovarian Cancer Association Consortium
Published: 2014
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190. Protein Z: A putative novel biomarker for early detection of ovarian cancer

Author: Russell, Matthew R., Walker, Michael J., Williamson, Andrew J. K., Gentry-Maharaj, Aleksandra, Ryan, Andy, Kalsi, Jatinderpal, Skates, Steven, DʼAmato, Alfonsina, Dive, Caroline, Pernemalm, Maria, Humphryes, Phillip C., Fourkala, Evangelia-Ourania, Whetton, Anthony D., Menon, Usha, Jacobs, Ian, and Graham, Robert L.J.
Published: 2016
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191. Association Between Menopausal Estrogen-Only Therapy and Ovarian Carcinoma Risk

Author: Lee, Alice W., Ness, Roberta B., Roman, Lynda D., Terry, Kathryn L., Schildkraut, Joellen M., Chang-Claude, Jenny, Doherty, Jennifer A., Menon, Usha, Cramer, Daniel W., Gayther, Simon A., Risch, Harvey, Gentry-Maharaj, Aleksandra, Goodman, Marc T., Modugno, Francesmary, Eilber, Ursula, Moysich, Kirsten B., Berchuck, Andrew, Rossing, Mary Anne, Jensen, Allan, Wicklund, Kristine G., Cushing-Haugen, Kara L., Hogdall, Estrid, Rudolph, Anja, Thompson, Pamela J., Wilkens, Lynne R., Kjaer, Susanne K., Carney, Michael E., Stram, Daniel O., Ramus, Susan J., Wu, Anna H., Pike, Malcolm C., and Pearce, Celeste Leigh
Published: 2016
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192. Comprehensive epithelial tubo-ovarian cancer risk prediction model incorporating genetic and epidemiological risk factors

Author: Lee, Andrew, primary, Yang, Xin, additional, Tyrer, Jonathan, additional, Gentry-Maharaj, Aleksandra, additional, Ryan, Andy, additional, Mavaddat, Nasim, additional, Cunningham, Alex P, additional, Carver, Tim, additional, Archer, Stephanie, additional, Leslie, Goska, additional, Kalsi, Jatinder, additional, Gaba, Faiza, additional, Manchanda, Ranjit, additional, Gayther, Simon, additional, Ramus, Susan J, additional, Walter, Fiona M, additional, Tischkowitz, Marc, additional, Jacobs, Ian, additional, Menon, Usha, additional, Easton, Douglas F, additional, Pharoah, Paul, additional, and Antoniou, Antonis C, additional
Published: 2021
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193. Prognostic and Immunological Significance of ARID1A Status in Endometriosis-Associated Ovarian Carcinoma

Author: Heinze, Karolin, primary, Nazeran, Tayyebeh M, additional, Lee, Sandra, additional, Kraemer, Pauline, additional, Cairns, Evan S, additional, Chiu, Derek S, additional, Leung, Samuel CY, additional, Kang, Eun-Young, additional, Meagher, Nicola S, additional, Kennedy, Catherine J, additional, Boros, Jessica, additional, Kommoss, Friedrich, additional, Vollert, Hans-Walter, additional, Heitze, Florian, additional, du Bois, Andreas, additional, Harter, Philipp, additional, Grube, Marcel, additional, Kraemer, Bernhard, additional, Staebler, Annette, additional, Kommoss, Felix K.F, additional, Heublein, Sabine, additional, Sinn, Peter, additional, Singh, Naveena, additional, Laslavic, Angela, additional, Elishaev, Esther, additional, Olawaiye, Alex, additional, Moysich, Kirsten, additional, Modugno, Francesmary, additional, Sharma, Raghwa, additional, Brand, Alison H, additional, Harnett, Paul R, additional, deFazio, Anna, additional, Fortner, Renee T, additional, Lubinski, Jan, additional, Lener, Marcin, additional, Toloczko-Grabarek, Aleksandra, additional, Cybulski, Cezary, additional, Gronwald, Helena, additional, Gronwald, Jacek, additional, Coulson, Penny, additional, El-Bahrawy, Mona A, additional, Jones, Michael E, additional, Schoemaker, Minouk J, additional, Swerdlow, Anthony J, additional, Gorringe, Kylie L, additional, Campbell, Ian, additional, Cook, Linda, additional, Gayther, Simon A, additional, Carney, Michael E, additional, Shvetsov, Yurii B, additional, Hernandez, Brenda B, additional, Wilkens, Lynne R, additional, Goodman, Marc T, additional, Mateoiu, Constantina, additional, Linder, Anna, additional, Sundfeldt, Karin, additional, Kelemen, Linda E, additional, Gentry-Maharaj, Aleksandra, additional, Widschwendter, Martin, additional, Menon, Usha, additional, Bolton, Kelly L, additional, Alsop, Jennifer, additional, Shah, Mitul, additional, Jimenez-Linan, Mercedes, additional, Pharoah, Paul DP, additional, Brenton, James D, additional, Cushing-Haugen, Kara L, additional, Harris, Holly R, additional, Doherty, Jennifer A, additional, Gilks, Blake, additional, Ghatage, Prafull, additional, Huntsman, David G, additional, Nelson, Gregg S, additional, Tinker, Anna V, additional, Lee, Cheng-Han, additional, Goode, Ellen L, additional, Nelson, Brad H, additional, Ramus, Susan J, additional, Kommoss, Stefan, additional, Talhouk, Aline, additional, Koebel, Martin, additional, and Anglesio, Michael S, additional
Published: 2021
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194. Ovarian Cancer Population Screening and Mortality After Long-Term Follow-up in the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS): A Randomised Controlled Trial

Author: Menon, Usha, primary, Gentry-Maharaj, Aleksandra, additional, Burnell, Matthew, additional, Singh, Naveena, additional, Ryan, Andy, additional, Karpinskyj, Chloe, additional, Carlino, Giulia, additional, Taylor, Julie, additional, Massingham, Susan K., additional, Raikou, Maria, additional, Kalsi, Jatinderpal K., additional, Woolas, Robert, additional, Manchanda, Ranjit, additional, Arora, Rupali, additional, Casey, Laura, additional, Dawnay, Anne, additional, Dobbs, Stephen, additional, Leeson, Simon, additional, Mould, Tim, additional, Seif, Mourad W., additional, Sharma, Aarti, additional, Williamson, Karin, additional, Liu, Yiling, additional, Fallowfield, Lesley, additional, McGuire, Alistair J., additional, Campbell, Stuart, additional, Skates, Steven J., additional, Jacobs, Ian J., additional, and Parmar, Mahesh, additional
Published: 2021
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195. Shared genetics underlying epidemiological association between endometriosis and ovarian cancer

Author: Lu, Yi, Cuellar-Partida, Gabriel, Painter, Jodie N., Nyholt, Dale R., Morris, Andrew P., 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, Wicklund, Kristine G., 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, Jensen, Allan, Giles, Graham G., Bruinsma, Fiona, Kjaer, Susanne K., Hildebrandt, Michelle A.T., Liang, Dong, Lu, Karen H., Wu, Xifeng, Bisogna, Maria, Dao, Fanny, Levine, Douglas A., Cramer, Daniel W., Terry, Kathryn L., Tworoger, Shelley S., Missmer, Stacey, Bjorge, Line, Salvesen, Helga B., Kopperud, Reidun K., Bischof, Katharina, Aben, Katja K.H., Kiemeney, Lambertus A., Massuger, Leon F.A.G., 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, Gawełko, Jan, 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, 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., Morgan, Terry K., Risch, Harvey A., Goode, Ellen L., Schildkraut, Joellen M., Webb, Penelope M., Pearce, Celeste L., Berchuck, Andrew, Pharoah, Paul D.P., Montgomery, Grant W., Zondervan, Krina T., Chenevix-Trench, Georgia, MacGregor, Stuart, Anderson, Carl A., Gordon, Scott D., Guo, Qun, Henders, Anjali K., Lambert, Ann, Lee, Sang Hong, Kraft, Peter, Kennedy, Stephen H., Macgregor, Stuart, Martin, Nicholas G., Missmer, Stacey A., Montgomery, Grant W., Morris, Andrew P., Nyholt, Dale R., Painter, Jodie N., Roseman, Fenella, Treloar, Susan A., Visscher, Peter M., Wallace, Leanne, and Zondervan, Krina T.
Published: 2015
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196. Sensitivity and specificity of multimodal and ultrasound screening for ovarian cancer, and stage distribution of detected cancers: results of the prevalence screen of the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS)

Author: Menon, Usha, Gentry-Maharaj, Aleksandra, Hallett, Rachel, Ryan, Andy, Burnell, Matthew, Sharma, Aarti, Lewis, Sara, Davies, Susan, Philpott, Susan, Lopes, Alberto, Godfrey, Keith, Oram, David, Herod, Jonathan, Williamson, Karin, Seif, Mourad W, Scott, Ian, Mould, Tim, Woolas, Robert, Murdoch, John, Dobbs, Stephen, Amso, Nazar N, Leeson, Simon, Cruickshank, Derek, Mcguire, Alistair, Campbell, Stuart, Fallowfield, Lesley, Singh, Naveena, Dawnay, Anne, Skates, Steven J, Parmar, Mahesh, and Jacobs, Ian
Published: 2009
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197. Cigarette smoking and risk of ovarian cancer: a pooled analysis of 21 case–control studies

Author: Faber, Mette T., Kjær, Susanne K., Dehlendorff, Christian, Chang-Claude, Jenny, Andersen, Klaus K., Høgdall, Estrid, Webb, Penelope M., Jordan, Susan J., Rossing, Mary Anne, Doherty, Jennifer A., Lurie, Galina, Thompson, Pamela J., Carney, Michael E., Goodman, Marc T., Ness, Roberta B., Modugno, Francesmary, Edwards, Robert P., Bunker, Clareann H., Goode, Ellen L., Fridley, Brooke L., Vierkant, Robert A., Larson, Melissa C., Schildkraut, Joellen, Cramer, Daniel W., Terry, Kathryn L., Vitonis, Allison F., Bandera, Elisa V., Olson, Sara H., King, Melony, Chandran, Urmila, Kiemeney, Lambertus A., Massuger, Leon F. A. G., van Altena, Anne M., Vermeulen, Sita H., Brinton, Louise, Wentzensen, Nicolas, Lissowska, Jolanta, Yang, Hannah P., Moysich, Kirsten B., Odunsi, Kunle, Kasza, Karin, Odunsi-Akanji, Oluwatosin, Song, Honglin, Pharaoh, Paul, Shah, Mitul, Whittemore, Alice S., McGuire, Valerie, Sieh, Weiva, Sutphen, Rebecca, Menon, Usha, Gayther, Simon A., Ramus, Susan J., Gentry-Maharaj, Aleksandra, Pearce, Celeste Leigh, Wu, Anna H., Pike, Malcolm C., Risch, Harvey A., Jensen, Allan, The Australian Cancer Study (Ovarian Cancer), Australian Ovarian Cancer Study Group, and On behalf of the Ovarian Cancer Association Consortium
Published: 2013
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198. Early detection of hereditary gynaecological cancers

Author: Gentry-Maharaj, Aleksandra, primary and Menon, Usha, additional
Published: 2014
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199. Computational learning methods for early detection of ovarian cancer

Author: Mariño, Ines P., primary, Vázquez, Manuel A., additional, Blyuss, Oleg, additional, Ryan, Andy, additional, Gentry-Maharaj, Aleksandra, additional, Kalsi, Jatinderpal, additional, Manchanda, Ranjit, additional, Jacobs, Ian, additional, Menon, Usha, additional, and Zaikin, Alexey, additional
Published: 2021
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200. Additional file 3 of Completeness and accuracy of national cancer and death registration for outcome ascertainment in trials—an ovarian cancer exemplar

Author: Jatinderpal K. Kalsi, Ryan, Andy, Gentry-Maharaj, Aleksandra, Margolin-Crump, Danielle, Naveena Singh, Burnell, Matthew, Benjamin, Elizabeth, Apostolidou, Sophia, Habib, Mariam, Massingham, Susan, Karpinskyj, Chloe, Woolas, Robert, Widschwendter, Martin, Fallowfield, Lesley, Campbell, Stuart, Skates, Steven, McGuire, Alistair, Parmar, Max, Jacobs, Ian, and Menon, Usha
Abstract: Additional file 3: Supplementary Figure 2. Outcomes Death Review Form.
Published: 2021
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