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1. 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, 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, 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

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Genetics, Ovarian Cancer, Clinical Research, Rare Diseases, Cancer, Aetiology, 2.1 Biological and endogenous factors, Humans, Female, Ovarian Neoplasms, Prognosis, Survival Analysis, RNA, Messenger, Cystadenocarcinoma, Serous, Biomarkers, Tumor, Forkhead Transcription Factors, AOCs group, Public Health and Health Services, Oncology & Carcinogenesis, Oncology and carcinogenesis
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 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

2. Gene expression profiling of mucinous ovarian tumors and comparison with upper and lower gastrointestinal tumors identifies markers associated with adverse outcomes.

Author

Meagher, Nicola S, Gorringe, Kylie L, Wakefield, Matthew, Bolithon, Adelyn, Pang, Chi Nam Ignatius, Chiu, Derek S, Anglesio, Michael S, Mallitt, Kylie-Ann, Doherty, Jennifer A, Harris, Holly R, Schildkraut, Joellen M, Berchuck, Andrew, Cushing-Haugen, Kara L, Chezar, Ksenia, Chou, Angela, Tan, Adeline, Alsop, Jennifer, Barlow, Ellen, Beckmann, Matthias W, Boros, Jessica, Bowtell, David DL, Group, for the AOCS, Brand, Alison H, Brenton, James D, Campbell, Ian, Cheasley, Dane, Cohen, Joshua, Cybulski, Cezary, Elishaev, Esther, Erber, Ramona, Farrell, Rhonda, Fischer, Anna, Fu, Zhuxuan, Gilks, Blake, Gill, Anthony J, Initiative, for the Australian Pancreatic Genome, Gourley, Charlie, Grube, Marcel, Harnett, Paul R, Hartmann, Arndt, Hettiaratchi, Anusha, Høgdall, Claus K, Huzarski, Tomasz, Jakubowska, Anna, Jimenez-Linan, Mercedes, Kennedy, Catherine J, Kim, Byoung-Gie, Kim, Jae-Weon, Kim, Jae-Hoon, Klett, Kayla, Koziak, Jennifer M, Lai, Tiffany, Laslavic, Angela, Lester, Jenny, Leung, Yee, Li, Na, Liauw, Winston, Lim, Belle WX, Linder, Anna, Lubiński, Jan, Mahale, Sakshi, Mateoiu, Constantina, McInerny, Simone, Menkiszak, Janusz, Minoo, Parham, Mittelstadt, Suzana, Morris, David, Orsulic, Sandra, Park, Sang-Yoon, Pearce, Celeste Leigh, Pearson, John V, Pike, Malcolm C, Quinn, Carmel M, Mohan, Ganendra Raj, Rao, Jianyu, Riggan, Marjorie J, Ruebner, Matthias, Salfinger, Stuart, Scott, Clare L, Shah, Mitul, Steed, Helen, Stewart, Colin JR, Subramanian, Deepak, Sung, Soseul, Tang, Katrina, Timpson, Paul, Ward, Robyn L, Wiedenhoefer, Rebekka, Thorne, Heather, Investigators, for the kConFab, Cohen, Paul A, Crowe, Philip, Fasching, Peter A, Gronwald, Jacek, Hawkins, Nicholas J, Høgdall, Estrid, Huntsman, David G, James, Paul A, Karlan, Beth Y, and Kelemen, Linda E

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Ovarian Cancer, Rare Diseases, Cancer, Digestive Diseases, Genetics, 4.1 Discovery and preclinical testing of markers and technologies, Detection, screening and diagnosis, Female, Humans, Neoplasm Staging, Ovarian Neoplasms, Carcinoma, Ovarian Epithelial, Adenocarcinoma, Mucinous, Prognosis, Gastrointestinal Neoplasms, AOCS Group, Australian Pancreatic Genome Initiative, kConFab Investigators, Oncology & Carcinogenesis, Clinical sciences, Oncology and carcinogenesis
Abstract

PurposeAdvanced-stage mucinous ovarian carcinoma (MOC) has poor chemotherapy response and prognosis and lacks biomarkers to aid stage I adjuvant treatment. Differentiating primary MOC from gastrointestinal (GI) metastases to the ovary is also challenging due to phenotypic similarities. Clinicopathologic and gene-expression data were analyzed to identify prognostic and diagnostic features.Experimental designDiscovery analyses selected 19 genes with prognostic/diagnostic potential. Validation was performed through the Ovarian Tumor Tissue Analysis consortium and GI cancer biobanks comprising 604 patients with MOC (n = 333), mucinous borderline ovarian tumors (MBOT, n = 151), and upper GI (n = 65) and lower GI tumors (n = 55).ResultsInfiltrative pattern of invasion was associated with decreased overall survival (OS) within 2 years from diagnosis, compared with expansile pattern in stage I MOC [hazard ratio (HR), 2.77; 95% confidence interval (CI), 1.04-7.41, P = 0.042]. Increased expression of THBS2 and TAGLN was associated with shorter OS in MOC patients (HR, 1.25; 95% CI, 1.04-1.51, P = 0.016) and (HR, 1.21; 95% CI, 1.01-1.45, P = 0.043), respectively. ERBB2 (HER2) amplification or high mRNA expression was evident in 64 of 243 (26%) of MOCs, but only 8 of 243 (3%) were also infiltrative (4/39, 10%) or stage III/IV (4/31, 13%).ConclusionsAn infiltrative growth pattern infers poor prognosis within 2 years from diagnosis and may help select stage I patients for adjuvant therapy. High expression of THBS2 and TAGLN in MOC confers an adverse prognosis and is upregulated in the infiltrative subtype, which warrants further investigation. Anti-HER2 therapy should be investigated in a subset of patients. MOC samples clustered with upper GI, yet markers to differentiate these entities remain elusive, suggesting similar underlying biology and shared treatment strategies.

Published
2022

3. Bilateral Oophorectomy and the Risk of Breast Cancer in BRCA1 Mutation Carriers: A Reappraisal.

Author

Kotsopoulos, Joanne, Lubinski, Jan, Gronwald, Jacek, Menkiszak, Janusz, McCuaig, Jeanna, Metcalfe, Kelly, Foulkes, William D, Neuhausen, Susan L, Sun, Sophie, Karlan, Beth Y, Eisen, Andrea, Tung, Nadine, Olopade, Olufunmilayo I, Couch, Fergus J, Huzarski, Tomasz, Senter, Leigha, Bordeleau, Louise, Singer, Christian F, Eng, Charis, Fruscio, Robert, Pal, Tuya, Sun, Ping, and Narod, Steven A

Subjects
Health Services and Systems, Biomedical and Clinical Sciences, Health Sciences, Oncology and Carcinogenesis, Breast Cancer, Cancer, Rare Diseases, Aging, Prevention, Patient Safety, Ovarian Cancer, Clinical Research, Adult, BRCA1 Protein, Breast Neoplasms, Female, Humans, Mutation, Odds Ratio, Ovarian Neoplasms, Ovariectomy, Risk, Medical and Health Sciences, Epidemiology, Biomedical and clinical sciences, Health sciences
Abstract

BackgroundThe lack of consensus on whether bilateral oophorectomy impacts risk of developing breast cancer among BRCA1 mutation carriers might be attributed to various biases, specifically, cancer-induced testing bias due to inclusion of prevalent cases. We conducted two complementary matched case-control analyses to evaluate the association of oophorectomy and BRCA1 breast cancer.MethodsA research questionnaire was administered every two years to collect information on exposures and disease. In the first analysis, we limited the study to prevalent breast cancer cases (diagnosed prior to study entry; n = 2,962) who were matched to controls on year of birth and country of residence (n = 4,358). In the second approach, we limited to 330 incident cases (diagnosed in the follow-up period) and 1,548 matched controls. Conditional logistic regression was used to estimate the adjusted odds ratios (OR) and 95% confidence intervals (CI) of invasive breast cancer.ResultsIn the first approach, there was a significant inverse association between oophorectomy and the risk of developing breast cancer [OR = 0.43; 95% confidence interval (CI), 0.34-0.55; P < 00001]. In the second approach, there was no association between oophorectomy and risk (OR = 1.21; 95% CI, 0.87-1.70; P = 0.26).ConclusionsThe inclusion of women with a personal history of breast cancer prior to ascertainment likely impacts upon the association of oophorectomy and BRCA1 breast cancer risk.ImpactOophorectomy is unlikely a determinant of breast cancer risk in BRCA1 mutation carriers but should be offered at age 35 to reduce the risk of ovarian and fallopian tube cancer.

Published
2022

4. eP160: Bilateral oophorectomy and the risk of breast cancer in women with a pathogenic variant in BRCA1: A reappraisal

Author

Kotsopoulos, joanne, Lubinski, Jan, Gronwald, Jacek, Menkiszak, Janusz, McCuaig, Jeanna, Metcalfe, Kelly, Foulkes, William, Neuhausen, Susan, Sun, Sophie, Karlan, Beth, Eisen, Andrea, Tung, Nadine, Olopade, Olufunmilayo, Couch, Fergus, Huzarski, Tomasz, Senter, Leigha, Bordeleau, Louise, Singer, Christian, Eng, Charis, Fruscio, Robert, Pal, Tuya, Sun, Ping, and Narod, Steven

Subjects
Biological Sciences, Genetics, Clinical Sciences, Genetics & Heredity
Published
2022

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

Author

Talhouk, Aline, George, Joshy, Wang, Chen, Budden, Timothy, Tan, Tuan Zea, Chiu, Derek S, Kommoss, Stefan, San Leong, Huei, Chen, Stephanie, Intermaggio, Maria P, Gilks, Blake, Nazeran, Tayyebeh M, Volchek, Mila, Elatre, Wafaa, Bentley, Rex C, Senz, Janine, Lum, Amy, Chow, Veronica, Sudderuddin, Hanwei, Mackenzie, Robertson, Leong, Samuel CY, Liu, Geyi, Johnson, Dustin, Chen, Billy, Group, AOCS, Alsop, Jennifer, Banerjee, Susana N, Behrens, Sabine, Bodelon, Clara, Brand, Alison H, Brinton, Louise, Carney, Michael E, Chiew, Yoke-Eng, Cushing-Haugen, Kara L, Cybulski, Cezary, Ennis, Darren, Fereday, Sian, Fortner, Renée T, García-Donas, Jesús, Gentry-Maharaj, Aleksandra, Glasspool, Rosalind, Goranova, Teodora, Greene, Casey S, Haluska, Paul, Harris, Holly R, Hendley, Joy, Hernandez, Brenda Y, Herpel, Esther, Jimenez-Linan, Mercedes, Karpinskyj, Chloe, Kaufmann, Scott H, Keeney, Gary L, Kennedy, Catherine J, Köbel, Martin, Koziak, Jennifer M, Larson, Melissa C, Lester, Jenny, Lewsley, Liz-Anne, Lissowska, Jolanta, Lubiński, Jan, Luk, Hugh, Macintyre, Geoff, Mahner, Sven, McNeish, Iain A, Menkiszak, Janusz, Nevins, Nikilyn, Osorio, Ana, Oszurek, Oleg, Palacios, José, Hinsley, Samantha, Pearce, Celeste L, Pike, Malcolm C, Piskorz, Anna M, Ray-Coquard, Isabelle, Rhenius, Valerie, Rodriguez-Antona, Cristina, Sharma, Raghwa, Sherman, Mark E, De Silva, Dilrini, Singh, Naveena, Sinn, Peter, Slamon, Dennis, Song, Honglin, Steed, Helen, Stronach, Euan A, Thompson, Pamela J, Tołoczko, Aleksandra, Trabert, Britton, Traficante, Nadia, Tseng, Chiu-Chen, Widschwendter, Martin, Wilkens, Lynne R, Winham, Stacey J, Winterhoff, Boris, Beeghly-Fadiel, Alicia, Benitez, Javier, Berchuck, Andrew, Brenton, James D, Brown, Robert, and Chang-Claude, Jenny

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Rare Diseases, Orphan Drug, Genetics, Ovarian Cancer, Women's Health, Cancer Genomics, Precision Medicine, Cancer, Human Genome, 4.2 Evaluation of markers and technologies, Good Health and Well Being, Aged, Algorithms, Cystadenoma, Serous, Female, Gene Expression Regulation, Neoplastic, Humans, Lymphocytes, Tumor-Infiltrating, Middle Aged, Neoplasm Grading, Neoplasm Proteins, Neoplasm, Residual, Ovarian Neoplasms, Transcriptome, Oncology & Carcinogenesis, Clinical sciences, Oncology and carcinogenesis
Abstract

PurposeGene expression-based molecular subtypes of high-grade serous tubo-ovarian cancer (HGSOC), demonstrated across multiple studies, may provide improved stratification for molecularly targeted trials. However, evaluation of clinical utility has been hindered by nonstandardized methods, which are not applicable in a clinical setting. We sought to generate a clinical grade minimal gene set assay for classification of individual tumor specimens into HGSOC subtypes and confirm previously reported subtype-associated features.Experimental designAdopting two independent approaches, we derived and internally validated algorithms for subtype prediction using published gene expression data from 1,650 tumors. We applied resulting models to NanoString data on 3,829 HGSOCs from the Ovarian Tumor Tissue Analysis consortium. We further developed, confirmed, and validated a reduced, minimal gene set predictor, with methods suitable for a single-patient setting.ResultsGene expression data were used to derive the predictor of high-grade serous ovarian carcinoma molecular subtype (PrOTYPE) assay. We established a de facto standard as a consensus of two parallel approaches. PrOTYPE subtypes are significantly associated with age, stage, residual disease, tumor-infiltrating lymphocytes, and outcome. The locked-down clinical grade PrOTYPE test includes a model with 55 genes that predicted gene expression subtype with >95% accuracy that was maintained in all analytic and biological validations.ConclusionsWe validated the PrOTYPE assay following the Institute of Medicine guidelines for the development of omics-based tests. This fully defined and locked-down clinical grade assay will enable trial design with molecular subtype stratification and allow for objective assessment of the predictive value of HGSOC molecular subtypes in precision medicine applications.See related commentary by McMullen et al., p. 5271.

Published
2020

7. Adult height is associated with increased risk of ovarian cancer: a Mendelian randomisation study

Author

Dixon-Suen, Suzanne C, Nagle, Christina M, Thrift, Aaron P, Pharoah, Paul DP, Ewing, Ailith, Pearce, Celeste Leigh, Zheng, Wei, Australian Ovarian Cancer Study Group, Chenevix-Trench, Georgia, Fasching, Peter A, Beckmann, Matthias W, Lambrechts, Diether, Vergote, Ignace, Lambrechts, Sandrina, Van Nieuwenhuysen, Els, Rossing, Mary Anne, Doherty, Jennifer A, Wicklund, Kristine G, Chang-Claude, Jenny, Jung, Audrey Y, Moysich, Kirsten B, Odunsi, Kunle, Goodman, Marc T, Wilkens, Lynne R, Thompson, Pamela J, Shvetsov, Yurii B, Dörk, Thilo, Park-Simon, Tjoung-Won, Hillemanns, Peter, Bogdanova, Natalia, Butzow, Ralf, Nevanlinna, Heli, Pelttari, Liisa M, Leminen, Arto, Modugno, Francesmary, Ness, Roberta B, Edwards, Robert P, Kelley, Joseph L, Heitz, Florian, du Bois, Andreas, Harter, Philipp, Schwaab, Ira, Karlan, Beth Y, Lester, Jenny, Orsulic, Sandra, Rimel, Bobbie J, Kjær, Susanne K, Høgdall, Estrid, Jensen, Allan, Goode, Ellen L, Fridley, Brooke L, Cunningham, Julie M, Winham, Stacey J, Giles, Graham G, Bruinsma, Fiona, Milne, Roger L, Southey, Melissa C, Hildebrandt, Michelle AT, Wu, Xifeng, Lu, Karen H, Liang, Dong, Levine, Douglas A, Bisogna, Maria, Schildkraut, Joellen M, Berchuck, Andrew, Cramer, Daniel W, Terry, Kathryn L, Bandera, Elisa V, Olson, Sara H, Salvesen, Helga B, Thomsen, Liv Cecilie Vestrheim, Kopperud, Reidun K, Bjorge, Line, Kiemeney, Lambertus A, Massuger, Leon FAG, Pejovic, Tanja, Bruegl, Amanda, Cook, Linda S, Le, Nhu D, Swenerton, Kenneth D, Brooks-Wilson, Angela, Kelemen, Linda E, Lubiński, Jan, Huzarski, Tomasz, Gronwald, Jacek, Menkiszak, Janusz, Wentzensen, Nicolas, Brinton, Louise, Yang, Hannah, Lissowska, Jolanta, Høgdall, Claus K, Lundvall, Lene, Song, Honglin, Tyrer, Jonathan P, Campbell, Ian, Eccles, Diana, Paul, James, Glasspool, Rosalind, Siddiqui, Nadeem, and Whittemore, Alice S

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Rare Diseases, Prevention, Genetics, Ovarian Cancer, Women's Health, Cancer, 2.1 Biological and endogenous factors, Adolescent, Adult, Aged, Aged, 80 and over, Body Height, Carcinoma, Ovarian Epithelial, Case-Control Studies, Female, Genetic Predisposition to Disease, Geography, Humans, Mendelian Randomization Analysis, Middle Aged, Ovarian Neoplasms, Risk Factors, Young Adult, Australian Ovarian Cancer Study Group, Ovarian Cancer Association Consortium, Public Health and Health Services, Oncology & Carcinogenesis, Oncology and carcinogenesis
Abstract

BackgroundObservational studies suggest greater height is associated with increased ovarian cancer risk, but cannot exclude bias and/or confounding as explanations for this. Mendelian randomisation (MR) can provide evidence which may be less prone to bias.MethodsWe pooled data from 39 Ovarian Cancer Association Consortium studies (16,395 cases; 23,003 controls). We applied two-stage predictor-substitution MR, using a weighted genetic risk score combining 609 single-nucleotide polymorphisms. Study-specific odds ratios (OR) and 95% confidence intervals (CI) for the association between genetically predicted height and risk were pooled using random-effects meta-analysis.ResultsGreater genetically predicted height was associated with increased ovarian cancer risk overall (pooled-OR (pOR) = 1.06; 95% CI: 1.01-1.11 per 5 cm increase in height), and separately for invasive (pOR = 1.06; 95% CI: 1.01-1.11) and borderline (pOR = 1.15; 95% CI: 1.02-1.29) tumours.ConclusionsWomen with a genetic propensity to being taller have increased risk of ovarian cancer. This suggests genes influencing height are involved in pathways promoting ovarian carcinogenesis.

Published
2018

8. MyD88 and TLR4 Expression in Epithelial Ovarian Cancer.

Author

Block, Matthew S, Vierkant, Robert A, Rambau, Peter F, Winham, Stacey J, Wagner, Philipp, Traficante, Nadia, Tołoczko, Aleksandra, Tiezzi, Daniel G, Taran, Florin Andrei, Sinn, Peter, Sieh, Weiva, Sharma, Raghwa, Rothstein, Joseph H, Ramón Y Cajal, Teresa, Paz-Ares, Luis, Oszurek, Oleg, Orsulic, Sandra, Ness, Roberta B, Nelson, Gregg, Modugno, Francesmary, Menkiszak, Janusz, McGuire, Valerie, McCauley, Bryan M, Mack, Marie, Lubiński, Jan, Longacre, Teri A, Li, Zheng, Lester, Jenny, Kennedy, Catherine J, Kalli, Kimberly R, Jung, Audrey Y, Johnatty, Sharon E, Jimenez-Linan, Mercedes, Jensen, Allan, Intermaggio, Maria P, Hung, Jillian, Herpel, Esther, Hernandez, Brenda Y, Hartkopf, Andreas D, Harnett, Paul R, Ghatage, Prafull, García-Bueno, José M, Gao, Bo, Fereday, Sian, Eilber, Ursula, Edwards, Robert P, de Sousa, Christiani B, de Andrade, Jurandyr M, Chudecka-Głaz, Anita, Chenevix-Trench, Georgia, Cazorla, Alicia, Brucker, Sara Y, Australian Ovarian Cancer Study Group, Alsop, Jennifer, Whittemore, Alice S, Steed, Helen, Staebler, Annette, Moysich, Kirsten B, Menon, Usha, Koziak, Jennifer M, Kommoss, Stefan, Kjaer, Susanne K, Kelemen, Linda E, Karlan, Beth Y, Huntsman, David G, Høgdall, Estrid, Gronwald, Jacek, Goodman, Marc T, Gilks, Blake, García, María José, Fasching, Peter A, de Fazio, Anna, Deen, Suha, Chang-Claude, Jenny, Candido Dos Reis, Francisco J, Campbell, Ian G, Brenton, James D, Bowtell, David D, Benítez, Javier, Pharoah, Paul DP, Köbel, Martin, Ramus, Susan J, and Goode, Ellen L

Subjects
Australian Ovarian Cancer Study Group, Humans, Ovarian Neoplasms, Tissue Array Analysis, Immunohistochemistry, Survival Analysis, Adult, Aged, Middle Aged, Female, Toll-Like Receptor 4, Myeloid Differentiation Factor 88, Biomarkers, Tumor, Carcinoma, Ovarian Epithelial, Biomarkers, Tumor, Carcinoma, Ovarian Epithelial, Medical and Health Sciences
Abstract

ObjectiveTo evaluate myeloid differentiation primary response gene 88 (MyD88) and Toll-like receptor 4 (TLR4) expression in relation to clinical features of epithelial ovarian cancer, histologic subtypes, and overall survival.Patients and methodsWe conducted centralized immunohistochemical staining, semi-quantitative scoring, and survival analysis in 5263 patients participating in the Ovarian Tumor Tissue Analysis consortium. Patients were diagnosed between January 1, 1978, and December 31, 2014, including 2865 high-grade serous ovarian carcinomas (HGSOCs), with more than 12,000 person-years of follow-up time. Tissue microarrays were stained for MyD88 and TLR4, and staining intensity was classified using a 2-tiered system for each marker (weak vs strong).ResultsExpression of MyD88 and TLR4 was similar in all histotypes except clear cell ovarian cancer, which showed reduced expression compared with other histotypes (P

Published
2018

9. 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, dos Reis, Francisco J Candido, 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 DP, Chenevix-Trench, Georgia, Huntsman, David G, Winham, Stacey J, Köbel, Martin, and Ramus, Susan J

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Immunology, Cancer, Prevention, Vaccine Related, Rare Diseases, Clinical Research, Ovarian Cancer, BRCA2 Protein, CD8 Antigens, Carcinoma, Ovarian Epithelial, Cohort Studies, Cystadenocarcinoma, Serous, Female, Humans, Lymphocytes, Tumor-Infiltrating, Middle Aged, Mutation, Neoplasm Grading, Ovarian Neoplasms, Prospective Studies, Survival Analysis, Treatment Outcome, Ovarian Tumor Tissue Analysis (OTTA) Consortium, Public Health and Health Services, Oncology and carcinogenesis
Abstract

ImportanceCytotoxic CD8+ tumor-infiltrating lymphocytes (TILs) participate in immune control of epithelial ovarian cancer; however, little is known about prognostic patterns of CD8+ TILs by histotype and in relation to other clinical factors.ObjectiveTo define the prognostic role of CD8+ TILs in epithelial ovarian cancer.Design, setting, and participantsThis was a multicenter observational, prospective survival cohort study of the Ovarian Tumor Tissue Analysis Consortium. More than 5500 patients, including 3196 with high-grade serous ovarian carcinomas (HGSOCs), were followed prospectively for over 24 650 person-years.ExposuresFollowing immunohistochemical analysis, CD8+ TILs were identified within the epithelial components of tumor islets. Patients were grouped based on the estimated number of CD8+ TILs per high-powered field: negative (none), low (1-2), moderate (3-19), and high (≥20). CD8+ TILs in a subset of patients were also assessed in a quantitative, uncategorized manner, and the functional form of associations with survival was assessed using penalized B-splines.Main outcomes and measuresOverall survival time.ResultsThe final sample included 5577 women; mean age at diagnosis was 58.4 years (median, 58.2 years). Among the 5 major invasive histotypes, HGSOCs showed the most infiltration. CD8+ TILs in HGSOCs were significantly associated with longer overall survival; median survival was 2.8 years for patients with no CD8+ TILs and 3.0 years, 3.8 years, and 5.1 years for patients with low, moderate, or high levels of CD8+ TILs, respectively (P value for trend = 4.2 × 10−16). A survival benefit was also observed among women with endometrioid and mucinous carcinomas, but not for those with the other histotypes. Among HGSOCs, CD8+ TILs were favorable regardless of extent of residual disease following cytoreduction, known standard treatment, and germline BRCA1 pathogenic mutation, but were not prognostic for BRCA2 mutation carriers. Evaluation of uncategorized CD8+ TIL counts showed a near-log-linear functional form.Conclusions and relevanceThis study demonstrates the histotype-specific nature of immune infiltration and provides definitive evidence for a dose-response relationship between CD8+ TILs and HGSOC survival. That the extent of infiltration is prognostic, not merely its presence or absence, suggests that understanding factors that drive infiltration will be the key to unraveling outcome heterogeneity in this cancer.

Published
2017

10. Dose-Response Association of CD8+ Tumor-Infiltrating Lymphocytes and Survival Time in High-Grade Serous Ovarian Cancer.

Author

Ovarian Tumor Tissue Analysis (OTTA) Consortium, 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, 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, Ursula, Eilber, McGuire, Valerie, Sieh, Weiva, Natanzon, Yanina, Li, Zheng, Whittemore, Alice S, Anna, deFazio, 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 DP, Chenevix-Trench, Georgia, Huntsman, David G, Winham, Stacey J, Köbel, Martin, and Ramus, Susan J

Subjects
Ovarian Tumor Tissue Analysis (OTTA) Consortium, Lymphocytes, Tumor-Infiltrating, Humans, Cystadenocarcinoma, Serous, Ovarian Neoplasms, BRCA2 Protein, Treatment Outcome, Survival Analysis, Cohort Studies, Prospective Studies, Mutation, Middle Aged, Female, Neoplasm Grading, CD8 Antigens, Carcinoma, Ovarian Epithelial, Lymphocytes, Tumor-Infiltrating, Cystadenocarcinoma, Serous, Carcinoma, Ovarian Epithelial, Cancer, Prevention, Ovarian Cancer, Rare Diseases, Vaccine Related, Clinical Research, Oncology and Carcinogenesis, Public Health and Health Services
Abstract

ImportanceCytotoxic CD8+ tumor-infiltrating lymphocytes (TILs) participate in immune control of epithelial ovarian cancer; however, little is known about prognostic patterns of CD8+ TILs by histotype and in relation to other clinical factors.ObjectiveTo define the prognostic role of CD8+ TILs in epithelial ovarian cancer.Design, setting, and participantsThis was a multicenter observational, prospective survival cohort study of the Ovarian Tumor Tissue Analysis Consortium. More than 5500 patients, including 3196 with high-grade serous ovarian carcinomas (HGSOCs), were followed prospectively for over 24 650 person-years.ExposuresFollowing immunohistochemical analysis, CD8+ TILs were identified within the epithelial components of tumor islets. Patients were grouped based on the estimated number of CD8+ TILs per high-powered field: negative (none), low (1-2), moderate (3-19), and high (≥20). CD8+ TILs in a subset of patients were also assessed in a quantitative, uncategorized manner, and the functional form of associations with survival was assessed using penalized B-splines.Main outcomes and measuresOverall survival time.ResultsThe final sample included 5577 women; mean age at diagnosis was 58.4 years (median, 58.2 years). Among the 5 major invasive histotypes, HGSOCs showed the most infiltration. CD8+ TILs in HGSOCs were significantly associated with longer overall survival; median survival was 2.8 years for patients with no CD8+ TILs and 3.0 years, 3.8 years, and 5.1 years for patients with low, moderate, or high levels of CD8+ TILs, respectively (P value for trend = 4.2 × 10−16). A survival benefit was also observed among women with endometrioid and mucinous carcinomas, but not for those with the other histotypes. Among HGSOCs, CD8+ TILs were favorable regardless of extent of residual disease following cytoreduction, known standard treatment, and germline BRCA1 pathogenic mutation, but were not prognostic for BRCA2 mutation carriers. Evaluation of uncategorized CD8+ TIL counts showed a near-log-linear functional form.Conclusions and relevanceThis study demonstrates the histotype-specific nature of immune infiltration and provides definitive evidence for a dose-response relationship between CD8+ TILs and HGSOC survival. That the extent of infiltration is prognostic, not merely its presence or absence, suggests that understanding factors that drive infiltration will be the key to unraveling outcome heterogeneity in this cancer.

Published
2017

11. Investigation of Exomic Variants Associated with Overall Survival in Ovarian Cancer

Author

Winham, Stacey J, Pirie, Ailith, Chen, Yian Ann, Larson, Melissa C, Fogarty, Zachary C, Earp, Madalene A, Anton-Culver, Hoda, Bandera, Elisa V, Cramer, Daniel, Doherty, Jennifer A, Goodman, Marc T, Gronwald, Jacek, Karlan, Beth Y, Kjaer, Susanne K, Levine, Douglas A, Menon, Usha, Ness, Roberta B, Pearce, Celeste L, Pejovic, Tanja, Rossing, Mary Anne, Wentzensen, Nicolas, Bean, Yukie T, Bisogna, Maria, Brinton, Louise A, Carney, Michael E, Cunningham, Julie M, Cybulski, Cezary, deFazio, Anna, Dicks, Ed M, Edwards, Robert P, Gayther, Simon A, Gentry-Maharaj, Aleksandra, Gore, Martin, Iversen, Edwin S, Jensen, Allan, Johnatty, Sharon E, Lester, Jenny, Lin, Hui-Yi, Lissowska, Jolanta, Lubinski, Jan, Menkiszak, Janusz, Modugno, Francesmary, Moysich, Kirsten B, Orlow, Irene, Pike, Malcolm C, Ramus, Susan J, Song, Honglin, Terry, Kathryn L, Thompson, Pamela J, Tyrer, Jonathan P, van den Berg, David J, Vierkant, Robert A, Vitonis, Allison F, Walsh, Christine, Wilkens, Lynne R, Wu, Anna H, Yang, Hannah, Ziogas, Argyrios, Berchuck, Andrew, Group, Georgia Chenevix-Trench on behalf of Australian Ovarian Cancer Study, Schildkraut, Joellen M, Permuth-Wey, Jennifer, Phelan, Catherine M, Pharoah, Paul DP, Fridley, Brooke L, Sellers, Thomas A, and Goode, Ellen L

Subjects
Epidemiology, Biomedical and Clinical Sciences, Health Sciences, Oncology and Carcinogenesis, Cancer, Genetics, Prevention, Clinical Research, Human Genome, Rare Diseases, Ovarian Cancer, 2.1 Biological and endogenous factors, Aetiology, Exome, Female, Genotype, Humans, Middle Aged, Ovarian Neoplasms, Survival Rate, Australian Ovarian Cancer Study Group, Medical and Health Sciences, Biomedical and clinical sciences, Health sciences
Abstract

BackgroundWhile numerous susceptibility loci for epithelial ovarian cancer (EOC) have been identified, few associations have been reported with overall survival. In the absence of common prognostic genetic markers, we hypothesize that rare coding variants may be associated with overall EOC survival and assessed their contribution in two exome-based genotyping projects of the Ovarian Cancer Association Consortium (OCAC).MethodsThe primary patient set (Set 1) included 14 independent EOC studies (4,293 patients) and 227,892 variants, and a secondary patient set (Set 2) included six additional EOC studies (1,744 patients) and 114,620 variants. Because power to detect rare variants individually is reduced, gene-level tests were conducted. Sets were analyzed separately at individual variants and by gene, and then combined with meta-analyses (73,203 variants and 13,163 genes overlapped).ResultsNo individual variant reached genome-wide statistical significance. A SNP previously implicated to be associated with EOC risk and, to a lesser extent, survival, rs8170, showed the strongest evidence of association with survival and similar effect size estimates across sets (Pmeta = 1.1E-6, HRSet1 = 1.17, HRSet2 = 1.14). Rare variants in ATG2B, an autophagy gene important for apoptosis, were significantly associated with survival after multiple testing correction (Pmeta = 1.1E-6; Pcorrected = 0.01).ConclusionsCommon variant rs8170 and rare variants in ATG2B may be associated with EOC overall survival, although further study is needed.ImpactThis study represents the first exome-wide association study of EOC survival to include rare variant analyses, and suggests that complementary single variant and gene-level analyses in large studies are needed to identify rare variants that warrant follow-up study. Cancer Epidemiol Biomarkers Prev; 25(3); 446-54. ©2016 AACR.

Published
2016

12. A combination of the immunohistochemical markers CK7 and SATB2 is highly sensitive and specific for distinguishing primary ovarian mucinous tumors from colorectal and appendiceal metastases

Author

Meagher, Nicola S., Wang, Linyuan, Rambau, Peter F., Intermaggio, Maria P., Huntsman, David G., Wilkens, Lynne R., El-Bahrawy, Mona A., Ness, Roberta B., Odunsi, Kunle, Steed, Helen, Herpel, Esther, Anglesio, Michael S., Zhang, Bonnie, Lambie, Neil, Swerdlow, Anthony J., Lubiński, Jan, Vierkant, Robert A., Goode, Ellen L., Menon, Usha, Toloczko-Grabarek, Aleksandra, Oszurek, Oleg, Bilic, Sanela, Talhouk, Aline, García-Closas, Montserrat, Wang, Qin, Tan, Adeline, Farrell, Rhonda, Kennedy, Catherine J., Jimenez-Linan, Mercedes, Sundfeldt, Karin, Etter, John L., Menkiszak, Janusz, Goodman, Marc T., Klonowski, Paul, Leung, Yee, Winham, Stacey J., Moysich, Kirsten B., Behrens, Sabine, Kluz, Tomasz, Edwards, Robert P., Gronwald, Jacek, Modugno, Francesmary, Hernandez, Brenda Y, Chow, Christine, Kelemen, Linda E., Keeney, Gary L., Carney, Michael E., Natanzon, Yanina, Robertson, Gregory, Sharma, Raghwa, Gayther, Simon A., Alsop, Jennifer, Luk, Hugh, Karpinskyj, Chloe, Campbell, Ian, Sinn, Peter, Gentry-Maharaj, Aleksandra, Coulson, Penny, Chang-Claude, Jenny, Shah, Mitul, Widschwendter, Martin, Tang, Katrina, Schoemaker, Minouk J., Koziak, Jennifer M., Cook, Linda S., Brenton, James D., Daley, Frances, Kristjansdottir, Björg, Mateoiu, Constantina, Larson, Melissa C., Harnett, Paul R., Jung, Audrey, deFazio, Anna, Gorringe, Kylie L., Pharoah, Paul D.P., Minoo, Parham, Stewart, Colin, Bathe, Oliver F., Gui, Xianyong, Cohen, Paul, Ramus, Susan J., and Köbel, Martin

Published
2019
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14. Variation in NF-κB Signaling Pathways and Survival in Invasive Epithelial Ovarian Cancer

Author

Block, Matthew S, Charbonneau, Bridget, Vierkant, Robert A, Fogarty, Zachary, Bamlet, William R, Pharoah, Paul DP, Chenevix-Trench, Georgia, AOCS, for, Group, ACS, Rossing, Mary Anne, Cramer, Daniel, Pearce, Celeste Leigh, Schildkraut, Joellen, Menon, Usha, Kjaer, Susanne K, Levine, Douglas A, Gronwald, Jacek, Culver, Hoda Anton, Whittemore, Alice S, Karlan, Beth Y, Lambrechts, Diether, Wentzensen, Nicolas, Kupryjanczyk, Jolanta, Chang-Claude, Jenny, Bandera, Elisa V, Hogdall, Estrid, Heitz, Florian, Kaye, Stanley B, Fasching, Peter A, Campbell, Ian, Goodman, Marc T, Pejovic, Tanja, Bean, Yukie T, Hays, Laura E, Lurie, Galina, Eccles, Diana, Hein, Alexander, Beckmann, Matthias W, Ekici, Arif B, Paul, James, Brown, Robert, Flanagan, James M, Harter, Philipp, du Bois, Andreas, Schwaab, Ira, Hogdall, Claus K, Lundvall, Lene, Olson, Sara H, Orlow, Irene, Paddock, Lisa E, Rudolph, Anja, Eilber, Ursula, Dansonka-Mieszkowska, Agnieszka, Rzepecka, Iwona K, Ziolkowska-Seta, Izabela, Brinton, Louise A, Yang, Hannah, Garcia-Closas, Montserrat, Despierre, Evelyn, Lambrechts, Sandrina, Vergote, Ignace, Walsh, Christine S, Lester, Jenny, Sieh, Weiva, McGuire, Valerie, Rothstein, Joseph H, Ziogas, Argyrios, Lubiński, Jan, Cybulski, Cezary, Menkiszak, Janusz, Jensen, Allan, Gayther, Simon A, Ramus, Susan J, Gentry-Maharaj, Aleksandra, Berchuck, Andrew, Wu, Anna H, Pike, Malcolm C, Van Den Berg, David, Terry, Kathryn L, Vitonis, Allison F, Ramirez, Starr M, Rider, David N, Knutson, Keith L, Sellers, Thomas A, Phelan, Catherine M, Doherty, Jennifer A, Johnatty, Sharon E, deFazio, Anna, Song, Honglin, Tyrer, Jonathan, Kalli, Kimberly R, Fridley, Brooke L, Cunningham, Julie M, and Goode, Ellen L

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Immunology, Prevention, Ovarian Cancer, Genetics, Rare Diseases, Cancer, Aetiology, 2.1 Biological and endogenous factors, Inflammatory and immune system, Adult, Aged, Carcinoma, Ovarian Epithelial, Female, Genotype, Humans, Middle Aged, NF-kappa B, Neoplasm Invasiveness, Neoplasms, Glandular and Epithelial, Ovarian Neoplasms, Polymorphism, Single Nucleotide, Proportional Hazards Models, Signal Transduction, Georgia Chenevix-Trench, for AOCS, /ACS Group, Medical and Health Sciences, Epidemiology, Biomedical and clinical sciences, Health sciences
Abstract

Survival in epithelial ovarian cancer (EOC) is influenced by the host immune response, yet the key genetic determinants of inflammation and immunity that affect prognosis are not known. The nuclear factor-κB (NF-κB) transcription factor family plays an important role in many immune and inflammatory responses, including the response to cancer. We studied common inherited variation in 210 genes in the NF-κB family in 10,084 patients with invasive EOC (5,248 high-grade serous, 1,452 endometrioid, 795 clear cell, and 661 mucinous) from the Ovarian Cancer Association Consortium. Associations between genotype and overall survival were assessed using Cox regression for all patients and by major histology, adjusting for known prognostic factors and correcting for multiple testing (threshold for statistical significance, P < 2.5 × 10(-5)). Results were statistically significant when assessed for patients of a single histology. Key associations were with caspase recruitment domain family, member 11 (CARD11) rs41324349 in patients with mucinous EOC [HR, 1.82; 95% confidence interval (CI), 1.41-2.35; P = 4.13 × 10(-6)] and tumor necrosis factor receptor superfamily, member 13B (TNFRSF13B) rs7501462 in patients with endometrioid EOC (HR, 0.68; 95% CI, 0.56-0.82; P = 2.33 × 10(-5)). Other associations of note included TNF receptor-associated factor 2 (TRAF2) rs17250239 in patients with high-grade serous EOC (HR, 0.84; 95% CI, 0.77-0.92; P = 6.49 × 10(-5)) and phospholipase C, gamma 1 (PLCG1) rs11696662 in patients with clear cell EOC (HR, 0.43; 95% CI, 0.26-0.73; P = 4.56 × 10(-4)). These associations highlight the potential importance of genes associated with host inflammation and immunity in modulating clinical outcomes in distinct EOC histologies.

Published
2014

15. Large-Scale Evaluation of Common Variation in Regulatory T Cell–Related Genes and Ovarian Cancer Outcome

Author

Charbonneau, Bridget, Moysich, Kirsten B, Kalli, Kimberly R, Oberg, Ann L, Vierkant, Robert A, Fogarty, Zachary C, Block, Matthew S, Maurer, Matthew J, Goergen, Krista M, Fridley, Brooke L, Cunningham, Julie M, Rider, David N, Preston, Claudia, Hartmann, Lynn C, Lawrenson, Kate, Wang, Chen, Tyrer, Jonathan, Song, Honglin, deFazio, Anna, Johnatty, Sharon E, Doherty, Jennifer A, Phelan, Catherine M, Sellers, Thomas A, Ramirez, Starr M, Vitonis, Allison F, Terry, Kathryn L, Van Den Berg, David, Pike, Malcolm C, Wu, Anna H, Berchuck, Andrew, Gentry-Maharaj, Aleksandra, Ramus, Susan J, Diergaarde, Brenda, Shen, Howard, Jensen, Allan, Menkiszak, Janusz, Cybulski, Cezary, Lubiński, Jan, Ziogas, Argyrios, Rothstein, Joseph H, McGuire, Valerie, Sieh, Weiva, Lester, Jenny, Walsh, Christine, Vergote, Ignace, Lambrechts, Sandrina, Despierre, Evelyn, Garcia-Closas, Montserrat, Yang, Hannah, Brinton, Louise A, Spiewankiewicz, Beata, Rzepecka, Iwona K, Dansonka-Mieszkowska, Agnieszka, Seibold, Petra, Rudolph, Anja, Paddock, Lisa E, Orlow, Irene, Lundvall, Lene, Olson, Sara H, Hogdall, Claus K, Schwaab, Ira, du Bois, Andreas, Harter, Philipp, Flanagan, James M, Brown, Robert, Paul, James, Ekici, Arif B, Beckmann, Matthias W, Hein, Alexander, Eccles, Diana, Lurie, Galina, Hays, Laura E, Bean, Yukie T, Pejovic, Tanja, Goodman, Marc T, Campbell, Ian, Fasching, Peter A, Konecny, Gottfried, Kaye, Stanley B, Heitz, Florian, Hogdall, Estrid, Bandera, Elisa V, Chang-Claude, Jenny, Kupryjanczyk, Jolanta, Wentzensen, Nicolas, Lambrechts, Diether, Karlan, Beth Y, Whittemore, Alice S, Culver, Hoda Anton, Gronwald, Jacek, Levine, Douglas A, Kjaer, Susanne K, Menon, Usha, Schildkraut, Joellen M, Pearce, Celeste Leigh, Cramer, Daniel W, Rossing, Mary Anne, Chenevix-Trench, Georgia, group, for the AOCS, and ACS

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Immunology, Cancer, Genetics, Clinical Research, Ovarian Cancer, Rare Diseases, Women's Health, 2.1 Biological and endogenous factors, Female, Gene Expression, Gene Expression Profiling, Genetic Predisposition to Disease, Genetic Variation, Germ-Line Mutation, Humans, Interleukin-2 Receptor alpha Subunit, Neoplasm Grading, Neoplasm Invasiveness, Ovarian Neoplasms, Patient Outcome Assessment, Polymorphism, Single Nucleotide, Prognosis, T-Lymphocytes, Regulatory, AOCS group, ACS, Pharmacology and Pharmaceutical Sciences, Oncology and carcinogenesis
Abstract

The presence of regulatory T cells (Treg) in solid tumors is known to play a role in patient survival in ovarian cancer and other malignancies. We assessed inherited genetic variations via 749 tag single-nucleotide polymorphisms (SNP) in 25 Treg-associated genes (CD28, CTLA4, FOXP3, IDO1, IL10, IL10RA, IL15, 1L17RA, IL23A, IL23R, IL2RA, IL6, IL6R, IL8, LGALS1, LGALS9, MAP3K8, STAT5A, STAT5B, TGFB1, TGFB2, TGFB3, TGFBR1, TGRBR2, and TGFBR3) in relation to ovarian cancer survival. We analyzed genotype and overall survival in 10,084 women with invasive epithelial ovarian cancer, including 5,248 high-grade serous, 1,452 endometrioid, 795 clear cell, and 661 mucinous carcinoma cases of European descent across 28 studies from the Ovarian Cancer Association Consortium (OCAC). The strongest associations were found for endometrioid carcinoma and IL2RA SNPs rs11256497 [HR, 1.42; 95% confidence interval (CI), 1.22-1.64; P = 5.7 × 10(-6)], rs791587 (HR, 1.36; 95% CI, 1.17-1.57; P = 6.2 × 10(-5)), rs2476491 (HR, = 1.40; 95% CI, 1.19-1.64; P = 5.6 × 10(-5)), and rs10795763 (HR, 1.35; 95% CI, 1.17-1.57; P = 7.9 × 10(-5)), and for clear cell carcinoma and CTLA4 SNP rs231775 (HR, 0.67; 95% CI, 0.54-0.82; P = 9.3 × 10(-5)) after adjustment for age, study site, population stratification, stage, grade, and oral contraceptive use. The rs231775 allele associated with improved survival in our study also results in an amino acid change in CTLA4 and previously has been reported to be associated with autoimmune conditions. Thus, we found evidence that SNPs in genes related to Tregs seem to play a role in ovarian cancer survival, particularly in patients with clear cell and endometrioid epithelial ovarian cancer.

Published
2014

16. Risk of ovarian cancer and the NF-κB pathway: genetic association with IL1A and TNFSF10.

Author

Charbonneau, Bridget, Block, Matthew, Bamlet, William, Vierkant, Robert, Kalli, Kimberly, Fogarty, Zachary, Rider, David, Sellers, Thomas, Tworoger, Shelley, Poole, Elizabeth, Risch, Harvey, Salvesen, Helga, Kiemeney, Lambertus, Baglietto, Laura, Giles, Graham, Severi, Gianluca, Trabert, Britton, Wentzensen, Nicolas, Chenevix-Trench, Georgia, Whittemore, Alice, Sieh, Weiva, Chang-Claude, Jenny, Bandera, Elisa, Orlow, Irene, Terry, Kathryn, Goodman, Marc, Thompson, Pamela, Cook, Linda, Rossing, Mary, Ness, Roberta, Narod, Steven, Kupryjanczyk, Jolanta, Lu, Karen, Butzow, Ralf, Dörk, Thilo, Pejovic, Tanja, Campbell, Ian, Le, Nhu, Bunker, Clareann, Bogdanova, Natalia, Runnebaum, Ingo, Eccles, Diana, Paul, James, Wu, Anna, Gayther, Simon, Hogdall, Estrid, Heitz, Florian, Kaye, Stanley, Walsh, Christine, Despierre, Evelyn, Brinton, Louise, Hein, Alexander, Rudolph, Anja, Dansonka-Mieszkowska, Agnieszka, Olson, Sara, Harter, Philipp, Tyrer, Jonathan, Vitonis, Allison, Brooks-Wilson, Angela, Aben, Katja, Pike, Malcolm, Ramus, Susan, Wik, Elisabeth, Cybulski, Cezary, Lin, Jie, Sucheston, Lara, Edwards, Robert, McGuire, Valerie, Lester, Jenny, du Bois, Andreas, Lundvall, Lene, Wang-Gohrke, Shan, Szafron, Lukasz, Lambrechts, Sandrina, Yang, Hannah, Beckmann, Matthias, Pelttari, Liisa, Van Altena, Anne, van den Berg, David, Halle, Mari, Gentry-Maharaj, Aleksandra, Schwaab, Ira, Chandran, Urmila, Menkiszak, Janusz, Ekici, Arif, Wilkens, Lynne, Leminen, Arto, Modugno, Francesmary, Friel, Grace, Rothstein, Joseph, Vergote, Ignace, Garcia-Closas, Montserrat, Hildebrandt, Michelle, Sobiczewski, Piotr, Kelemen, Linda, Pharoah, Paul, Moysich, Kirsten, Knutson, Keith, Cunningham, Julie, and Fridley, Brooke

Subjects
Case-Control Studies, Female, Genetic Association Studies, Humans, Interleukin-1alpha, NF-kappa B, Ovarian Neoplasms, Polymorphism, Single Nucleotide, Risk, Signal Transduction, TNF-Related Apoptosis-Inducing Ligand
Abstract

A missense single-nucleotide polymorphism (SNP) in the immune modulatory gene IL1A has been associated with ovarian cancer risk (rs17561). Although the exact mechanism through which this SNP alters risk of ovarian cancer is not clearly understood, rs17561 has also been associated with risk of endometriosis, an epidemiologic risk factor for ovarian cancer. Interleukin-1α (IL1A) is both regulated by and able to activate NF-κB, a transcription factor family that induces transcription of many proinflammatory genes and may be an important mediator in carcinogenesis. We therefore tagged SNPs in more than 200 genes in the NF-κB pathway for a total of 2,282 SNPs (including rs17561) for genotype analysis of 15,604 cases of ovarian cancer in patients of European descent, including 6,179 of high-grade serous (HGS), 2,100 endometrioid, 1,591 mucinous, 1,034 clear cell, and 1,016 low-grade serous, including 23,235 control cases spanning 40 studies in the Ovarian Cancer Association Consortium. In this large population, we confirmed the association between rs17561 and clear cell ovarian cancer [OR, 0.84; 95% confidence interval (CI), 0.76-0.93; P = 0.00075], which remained intact even after excluding participants in the prior study (OR, 0.85; 95% CI, 0.75-0.95; P = 0.006). Considering a multiple-testing-corrected significance threshold of P < 2.5 × 10(-5), only one other variant, the TNFSF10 SNP rs6785617, was associated significantly with a risk of ovarian cancer (low malignant potential tumors OR, 0.85; 95% CI, 0.79-0.91; P = 0.00002). Our results extend the evidence that borderline tumors may have a distinct genetic etiology. Further investigation of how these SNPs might modify ovarian cancer associations with other inflammation-related risk factors is warranted.

Published
2014

18. Risk model in women with ovarian cancer without mutations

Author

Cymbaluk-Płoska Aneta, Chudecka-Głaz Anita, Sompolska-Rzechuła Agnieszka, Rasinska Kamila, Dubiel Paulina, and Menkiszak Janusz

Subjects
logit, mathematical model, ovarian cancer, risk factor, Medicine
Abstract

Ovarian cancer is characterised by the greatest mortality among all tumors of the reproductive tract.

Published
2018
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19. Data from Large-Scale Evaluation of Common Variation in Regulatory T Cell–Related Genes and Ovarian Cancer Outcome

Author

Charbonneau, Bridget, primary, Moysich, Kirsten B., primary, Kalli, Kimberly R., primary, Oberg, Ann L., primary, Vierkant, Robert A., primary, Fogarty, Zachary C., primary, Block, Matthew S., primary, Maurer, Matthew J., primary, Goergen, Krista M., primary, Fridley, Brooke L., primary, Cunningham, Julie M., primary, Rider, David N., primary, Preston, Claudia, primary, Hartmann, Lynn C., primary, Lawrenson, Kate, primary, Wang, Chen, primary, Tyrer, Jonathan, primary, Song, Honglin, primary, deFazio, Anna, primary, Johnatty, Sharon E., primary, Doherty, Jennifer A., primary, Phelan, Catherine M., primary, Sellers, Thomas A., primary, Ramirez, Starr M., primary, Vitonis, Allison F., primary, Terry, Kathryn L., primary, Van Den Berg, David, primary, Pike, Malcolm C., primary, Wu, Anna H., primary, Berchuck, Andrew, primary, Gentry-Maharaj, Aleksandra, primary, Ramus, Susan J., primary, Diergaarde, Brenda, primary, Shen, Howard, primary, Jensen, Allan, primary, Menkiszak, Janusz, primary, Cybulski, Cezary, primary, Lubiński, Jan, primary, Ziogas, Argyrios, primary, Rothstein, Joseph H., primary, McGuire, Valerie, primary, Sieh, Weiva, primary, Lester, Jenny, primary, Walsh, Christine, primary, Vergote, Ignace, primary, Lambrechts, Sandrina, primary, Despierre, Evelyn, primary, Garcia-Closas, Montserrat, primary, Yang, Hannah, primary, Brinton, Louise A., primary, Spiewankiewicz, Beata, primary, Rzepecka, Iwona K., primary, Dansonka-Mieszkowska, Agnieszka, primary, Seibold, Petra, primary, Rudolph, Anja, primary, Paddock, Lisa E., primary, Orlow, Irene, primary, Lundvall, Lene, primary, Olson, Sara H., primary, Hogdall, Claus K., primary, Schwaab, Ira, primary, du Bois, Andreas, primary, Harter, Philipp, primary, Flanagan, James M., primary, Brown, Robert, primary, Paul, James, primary, Ekici, Arif B., primary, Beckmann, Matthias W., primary, Hein, Alexander, primary, Eccles, Diana, primary, Lurie, Galina, primary, Hays, Laura E., primary, Bean, Yukie T., primary, Pejovic, Tanja, primary, Goodman, Marc T., primary, Campbell, Ian, primary, Fasching, Peter A., primary, Konecny, Gottfried, primary, Kaye, Stanley B., primary, Heitz, Florian, primary, Hogdall, Estrid, primary, Bandera, Elisa V., primary, Chang-Claude, Jenny, primary, Kupryjanczyk, Jolanta, primary, Wentzensen, Nicolas, primary, Lambrechts, Diether, primary, Karlan, Beth Y., primary, Whittemore, Alice S., primary, Culver, Hoda Anton, primary, Gronwald, Jacek, primary, Levine, Douglas A., primary, Kjaer, Susanne K., primary, Menon, Usha, primary, Schildkraut, Joellen M., primary, Pearce, Celeste Leigh, primary, Cramer, Daniel W., primary, Rossing, Mary Anne, primary, Chenevix-Trench, Georgia, primary, Pharoah, Paul D.P., primary, Gayther, Simon A., primary, Ness, Roberta B., primary, Odunsi, Kunle, primary, Sucheston, Lara E., primary, Knutson, Keith L., primary, and Goode, Ellen L., primary

Published
2023
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20. Supplementary Tables 1 - 4 from Large-Scale Evaluation of Common Variation in Regulatory T Cell–Related Genes and Ovarian Cancer Outcome

Author

Charbonneau, Bridget, primary, Moysich, Kirsten B., primary, Kalli, Kimberly R., primary, Oberg, Ann L., primary, Vierkant, Robert A., primary, Fogarty, Zachary C., primary, Block, Matthew S., primary, Maurer, Matthew J., primary, Goergen, Krista M., primary, Fridley, Brooke L., primary, Cunningham, Julie M., primary, Rider, David N., primary, Preston, Claudia, primary, Hartmann, Lynn C., primary, Lawrenson, Kate, primary, Wang, Chen, primary, Tyrer, Jonathan, primary, Song, Honglin, primary, deFazio, Anna, primary, Johnatty, Sharon E., primary, Doherty, Jennifer A., primary, Phelan, Catherine M., primary, Sellers, Thomas A., primary, Ramirez, Starr M., primary, Vitonis, Allison F., primary, Terry, Kathryn L., primary, Van Den Berg, David, primary, Pike, Malcolm C., primary, Wu, Anna H., primary, Berchuck, Andrew, primary, Gentry-Maharaj, Aleksandra, primary, Ramus, Susan J., primary, Diergaarde, Brenda, primary, Shen, Howard, primary, Jensen, Allan, primary, Menkiszak, Janusz, primary, Cybulski, Cezary, primary, Lubiński, Jan, primary, Ziogas, Argyrios, primary, Rothstein, Joseph H., primary, McGuire, Valerie, primary, Sieh, Weiva, primary, Lester, Jenny, primary, Walsh, Christine, primary, Vergote, Ignace, primary, Lambrechts, Sandrina, primary, Despierre, Evelyn, primary, Garcia-Closas, Montserrat, primary, Yang, Hannah, primary, Brinton, Louise A., primary, Spiewankiewicz, Beata, primary, Rzepecka, Iwona K., primary, Dansonka-Mieszkowska, Agnieszka, primary, Seibold, Petra, primary, Rudolph, Anja, primary, Paddock, Lisa E., primary, Orlow, Irene, primary, Lundvall, Lene, primary, Olson, Sara H., primary, Hogdall, Claus K., primary, Schwaab, Ira, primary, du Bois, Andreas, primary, Harter, Philipp, primary, Flanagan, James M., primary, Brown, Robert, primary, Paul, James, primary, Ekici, Arif B., primary, Beckmann, Matthias W., primary, Hein, Alexander, primary, Eccles, Diana, primary, Lurie, Galina, primary, Hays, Laura E., primary, Bean, Yukie T., primary, Pejovic, Tanja, primary, Goodman, Marc T., primary, Campbell, Ian, primary, Fasching, Peter A., primary, Konecny, Gottfried, primary, Kaye, Stanley B., primary, Heitz, Florian, primary, Hogdall, Estrid, primary, Bandera, Elisa V., primary, Chang-Claude, Jenny, primary, Kupryjanczyk, Jolanta, primary, Wentzensen, Nicolas, primary, Lambrechts, Diether, primary, Karlan, Beth Y., primary, Whittemore, Alice S., primary, Culver, Hoda Anton, primary, Gronwald, Jacek, primary, Levine, Douglas A., primary, Kjaer, Susanne K., primary, Menon, Usha, primary, Schildkraut, Joellen M., primary, Pearce, Celeste Leigh, primary, Cramer, Daniel W., primary, Rossing, Mary Anne, primary, Chenevix-Trench, Georgia, primary, Pharoah, Paul D.P., primary, Gayther, Simon A., primary, Ness, Roberta B., primary, Odunsi, Kunle, primary, Sucheston, Lara E., primary, Knutson, Keith L., primary, and Goode, Ellen L., primary

Published
2023
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21. Figure S6A from Investigation of Exomic Variants Associated with Overall Survival in Ovarian Cancer

Author

Winham, Stacey J., primary, Pirie, Ailith, primary, Chen, Yian Ann, primary, Larson, Melissa C., primary, Fogarty, Zachary C., primary, Earp, Madalene A., primary, Anton-Culver, Hoda, primary, Bandera, Elisa V., primary, Cramer, Daniel, primary, Doherty, Jennifer A., primary, Goodman, Marc T., primary, Gronwald, Jacek, primary, Karlan, Beth Y., primary, Kjaer, Susanne K., primary, Levine, Douglas A., primary, Menon, Usha, primary, Ness, Roberta B., primary, Pearce, Celeste L., primary, Pejovic, Tanja, primary, Rossing, Mary Anne, primary, Wentzensen, Nicolas, primary, Bean, Yukie T., primary, Bisogna, Maria, primary, Brinton, Louise A., primary, Carney, Michael E., primary, Cunningham, Julie M., primary, Cybulski, Cezary, primary, deFazio, Anna, primary, Dicks, Ed M., primary, Edwards, Robert P., primary, Gayther, Simon A., primary, Gentry-Maharaj, Aleksandra, primary, Gore, Martin, primary, Iversen, Edwin S., primary, Jensen, Allan, primary, Johnatty, Sharon E., primary, Lester, Jenny, primary, Lin, Hui-Yi, primary, Lissowska, Jolanta, primary, Lubinski, Jan, primary, Menkiszak, Janusz, primary, Modugno, Francesmary, primary, Moysich, Kirsten B., primary, Orlow, Irene, primary, Pike, Malcolm C., primary, Ramus, Susan J., primary, Song, Honglin, primary, Terry, Kathryn L., primary, Thompson, Pamela J., primary, Tyrer, Jonathan P., primary, van den Berg, David J., primary, Vierkant, Robert A., primary, Vitonis, Allison F., primary, Walsh, Christine, primary, Wilkens, Lynne R., primary, Wu, Anna H., primary, Yang, Hannah, primary, Ziogas, Argyrios, primary, Berchuck, Andrew, primary, Schildkraut, Joellen M., primary, Permuth-Wey, Jennifer, primary, Phelan, Catherine M., primary, Pharoah, Paul D.P., primary, Fridley, Brooke L., primary, Sellers, Thomas A., primary, and Goode, Ellen L., primary

Published
2023
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22. Supplemental Figure Legends from Investigation of Exomic Variants Associated with Overall Survival in Ovarian Cancer

Author

Winham, Stacey J., primary, Pirie, Ailith, primary, Chen, Yian Ann, primary, Larson, Melissa C., primary, Fogarty, Zachary C., primary, Earp, Madalene A., primary, Anton-Culver, Hoda, primary, Bandera, Elisa V., primary, Cramer, Daniel, primary, Doherty, Jennifer A., primary, Goodman, Marc T., primary, Gronwald, Jacek, primary, Karlan, Beth Y., primary, Kjaer, Susanne K., primary, Levine, Douglas A., primary, Menon, Usha, primary, Ness, Roberta B., primary, Pearce, Celeste L., primary, Pejovic, Tanja, primary, Rossing, Mary Anne, primary, Wentzensen, Nicolas, primary, Bean, Yukie T., primary, Bisogna, Maria, primary, Brinton, Louise A., primary, Carney, Michael E., primary, Cunningham, Julie M., primary, Cybulski, Cezary, primary, deFazio, Anna, primary, Dicks, Ed M., primary, Edwards, Robert P., primary, Gayther, Simon A., primary, Gentry-Maharaj, Aleksandra, primary, Gore, Martin, primary, Iversen, Edwin S., primary, Jensen, Allan, primary, Johnatty, Sharon E., primary, Lester, Jenny, primary, Lin, Hui-Yi, primary, Lissowska, Jolanta, primary, Lubinski, Jan, primary, Menkiszak, Janusz, primary, Modugno, Francesmary, primary, Moysich, Kirsten B., primary, Orlow, Irene, primary, Pike, Malcolm C., primary, Ramus, Susan J., primary, Song, Honglin, primary, Terry, Kathryn L., primary, Thompson, Pamela J., primary, Tyrer, Jonathan P., primary, van den Berg, David J., primary, Vierkant, Robert A., primary, Vitonis, Allison F., primary, Walsh, Christine, primary, Wilkens, Lynne R., primary, Wu, Anna H., primary, Yang, Hannah, primary, Ziogas, Argyrios, primary, Berchuck, Andrew, primary, Schildkraut, Joellen M., primary, Permuth-Wey, Jennifer, primary, Phelan, Catherine M., primary, Pharoah, Paul D.P., primary, Fridley, Brooke L., primary, Sellers, Thomas A., primary, and Goode, Ellen L., primary

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2023
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23. Supplemental Tables from Investigation of Exomic Variants Associated with Overall Survival in Ovarian Cancer

Author

Winham, Stacey J., primary, Pirie, Ailith, primary, Chen, Yian Ann, primary, Larson, Melissa C., primary, Fogarty, Zachary C., primary, Earp, Madalene A., primary, Anton-Culver, Hoda, primary, Bandera, Elisa V., primary, Cramer, Daniel, primary, Doherty, Jennifer A., primary, Goodman, Marc T., primary, Gronwald, Jacek, primary, Karlan, Beth Y., primary, Kjaer, Susanne K., primary, Levine, Douglas A., primary, Menon, Usha, primary, Ness, Roberta B., primary, Pearce, Celeste L., primary, Pejovic, Tanja, primary, Rossing, Mary Anne, primary, Wentzensen, Nicolas, primary, Bean, Yukie T., primary, Bisogna, Maria, primary, Brinton, Louise A., primary, Carney, Michael E., primary, Cunningham, Julie M., primary, Cybulski, Cezary, primary, deFazio, Anna, primary, Dicks, Ed M., primary, Edwards, Robert P., primary, Gayther, Simon A., primary, Gentry-Maharaj, Aleksandra, primary, Gore, Martin, primary, Iversen, Edwin S., primary, Jensen, Allan, primary, Johnatty, Sharon E., primary, Lester, Jenny, primary, Lin, Hui-Yi, primary, Lissowska, Jolanta, primary, Lubinski, Jan, primary, Menkiszak, Janusz, primary, Modugno, Francesmary, primary, Moysich, Kirsten B., primary, Orlow, Irene, primary, Pike, Malcolm C., primary, Ramus, Susan J., primary, Song, Honglin, primary, Terry, Kathryn L., primary, Thompson, Pamela J., primary, Tyrer, Jonathan P., primary, van den Berg, David J., primary, Vierkant, Robert A., primary, Vitonis, Allison F., primary, Walsh, Christine, primary, Wilkens, Lynne R., primary, Wu, Anna H., primary, Yang, Hannah, primary, Ziogas, Argyrios, primary, Berchuck, Andrew, primary, Schildkraut, Joellen M., primary, Permuth-Wey, Jennifer, primary, Phelan, Catherine M., primary, Pharoah, Paul D.P., primary, Fridley, Brooke L., primary, Sellers, Thomas A., primary, and Goode, Ellen L., primary

Published
2023
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24. Data from Variation in NF-κB Signaling Pathways and Survival in Invasive Epithelial Ovarian Cancer

Author

Block, Matthew S., primary, Charbonneau, Bridget, primary, Vierkant, Robert A., primary, Fogarty, Zachary, primary, Bamlet, William R., primary, Pharoah, Paul D.P., primary, Rossing, Mary Anne, primary, Cramer, Daniel, primary, Pearce, Celeste Leigh, primary, Schildkraut, Joellen, primary, Menon, Usha, primary, Kjaer, Susanne K., primary, Levine, Douglas A., primary, Gronwald, Jacek, primary, Culver, Hoda Anton, primary, Whittemore, Alice S., primary, Karlan, Beth Y., primary, Lambrechts, Diether, primary, Wentzensen, Nicolas, primary, Kupryjanczyk, Jolanta, primary, Chang-Claude, Jenny, primary, Bandera, Elisa V., primary, Hogdall, Estrid, primary, Heitz, Florian, primary, Kaye, Stanley B., primary, Fasching, Peter A., primary, Campbell, Ian, primary, Goodman, Marc T., primary, Pejovic, Tanja, primary, Bean, Yukie T., primary, Hays, Laura E., primary, Lurie, Galina, primary, Eccles, Diana, primary, Hein, Alexander, primary, Beckmann, Matthias W., primary, Ekici, Arif B., primary, Paul, James, primary, Brown, Robert, primary, Flanagan, James M., primary, Harter, Philipp, primary, du Bois, Andreas, primary, Schwaab, Ira, primary, Hogdall, Claus K., primary, Lundvall, Lene, primary, Olson, Sara H., primary, Orlow, Irene, primary, Paddock, Lisa E., primary, Rudolph, Anja, primary, Eilber, Ursula, primary, Dansonka-Mieszkowska, Agnieszka, primary, Rzepecka, Iwona K., primary, Ziolkowska-Seta, Izabela, primary, Brinton, Louise A., primary, Yang, Hannah, primary, Garcia-Closas, Montserrat, primary, Despierre, Evelyn, primary, Lambrechts, Sandrina, primary, Vergote, Ignace, primary, Walsh, Christine S., primary, Lester, Jenny, primary, Sieh, Weiva, primary, McGuire, Valerie, primary, Rothstein, Joseph H., primary, Ziogas, Argyrios, primary, Lubiński, Jan, primary, Cybulski, Cezary, primary, Menkiszak, Janusz, primary, Jensen, Allan, primary, Gayther, Simon A., primary, Ramus, Susan J., primary, Gentry-Maharaj, Aleksandra, primary, Berchuck, Andrew, primary, Wu, Anna H., primary, Pike, Malcolm C., primary, Van Den Berg, David, primary, Terry, Kathryn L., primary, Vitonis, Allison F., primary, Ramirez, Starr M., primary, Rider, David N., primary, Knutson, Keith L., primary, Sellers, Thomas A., primary, Phelan, Catherine M., primary, Doherty, Jennifer A., primary, Johnatty, Sharon E., primary, deFazio, Anna, primary, Song, Honglin, primary, Tyrer, Jonathan, primary, Kalli, Kimberly R., primary, Fridley, Brooke L., primary, Cunningham, Julie M., primary, and Goode, Ellen L., primary

Published
2023
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25. Data from Investigation of Exomic Variants Associated with Overall Survival in Ovarian Cancer

Author

Winham, Stacey J., primary, Pirie, Ailith, primary, Chen, Yian Ann, primary, Larson, Melissa C., primary, Fogarty, Zachary C., primary, Earp, Madalene A., primary, Anton-Culver, Hoda, primary, Bandera, Elisa V., primary, Cramer, Daniel, primary, Doherty, Jennifer A., primary, Goodman, Marc T., primary, Gronwald, Jacek, primary, Karlan, Beth Y., primary, Kjaer, Susanne K., primary, Levine, Douglas A., primary, Menon, Usha, primary, Ness, Roberta B., primary, Pearce, Celeste L., primary, Pejovic, Tanja, primary, Rossing, Mary Anne, primary, Wentzensen, Nicolas, primary, Bean, Yukie T., primary, Bisogna, Maria, primary, Brinton, Louise A., primary, Carney, Michael E., primary, Cunningham, Julie M., primary, Cybulski, Cezary, primary, deFazio, Anna, primary, Dicks, Ed M., primary, Edwards, Robert P., primary, Gayther, Simon A., primary, Gentry-Maharaj, Aleksandra, primary, Gore, Martin, primary, Iversen, Edwin S., primary, Jensen, Allan, primary, Johnatty, Sharon E., primary, Lester, Jenny, primary, Lin, Hui-Yi, primary, Lissowska, Jolanta, primary, Lubinski, Jan, primary, Menkiszak, Janusz, primary, Modugno, Francesmary, primary, Moysich, Kirsten B., primary, Orlow, Irene, primary, Pike, Malcolm C., primary, Ramus, Susan J., primary, Song, Honglin, primary, Terry, Kathryn L., primary, Thompson, Pamela J., primary, Tyrer, Jonathan P., primary, van den Berg, David J., primary, Vierkant, Robert A., primary, Vitonis, Allison F., primary, Walsh, Christine, primary, Wilkens, Lynne R., primary, Wu, Anna H., primary, Yang, Hannah, primary, Ziogas, Argyrios, primary, Berchuck, Andrew, primary, Schildkraut, Joellen M., primary, Permuth-Wey, Jennifer, primary, Phelan, Catherine M., primary, Pharoah, Paul D.P., primary, Fridley, Brooke L., primary, Sellers, Thomas A., primary, and Goode, Ellen L., primary

Published
2023
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26. Supplementary Tables 1 through 3 from Variation in NF-κB Signaling Pathways and Survival in Invasive Epithelial Ovarian Cancer

Author

Block, Matthew S., primary, Charbonneau, Bridget, primary, Vierkant, Robert A., primary, Fogarty, Zachary, primary, Bamlet, William R., primary, Pharoah, Paul D.P., primary, Rossing, Mary Anne, primary, Cramer, Daniel, primary, Pearce, Celeste Leigh, primary, Schildkraut, Joellen, primary, Menon, Usha, primary, Kjaer, Susanne K., primary, Levine, Douglas A., primary, Gronwald, Jacek, primary, Culver, Hoda Anton, primary, Whittemore, Alice S., primary, Karlan, Beth Y., primary, Lambrechts, Diether, primary, Wentzensen, Nicolas, primary, Kupryjanczyk, Jolanta, primary, Chang-Claude, Jenny, primary, Bandera, Elisa V., primary, Hogdall, Estrid, primary, Heitz, Florian, primary, Kaye, Stanley B., primary, Fasching, Peter A., primary, Campbell, Ian, primary, Goodman, Marc T., primary, Pejovic, Tanja, primary, Bean, Yukie T., primary, Hays, Laura E., primary, Lurie, Galina, primary, Eccles, Diana, primary, Hein, Alexander, primary, Beckmann, Matthias W., primary, Ekici, Arif B., primary, Paul, James, primary, Brown, Robert, primary, Flanagan, James M., primary, Harter, Philipp, primary, du Bois, Andreas, primary, Schwaab, Ira, primary, Hogdall, Claus K., primary, Lundvall, Lene, primary, Olson, Sara H., primary, Orlow, Irene, primary, Paddock, Lisa E., primary, Rudolph, Anja, primary, Eilber, Ursula, primary, Dansonka-Mieszkowska, Agnieszka, primary, Rzepecka, Iwona K., primary, Ziolkowska-Seta, Izabela, primary, Brinton, Louise A., primary, Yang, Hannah, primary, Garcia-Closas, Montserrat, primary, Despierre, Evelyn, primary, Lambrechts, Sandrina, primary, Vergote, Ignace, primary, Walsh, Christine S., primary, Lester, Jenny, primary, Sieh, Weiva, primary, McGuire, Valerie, primary, Rothstein, Joseph H., primary, Ziogas, Argyrios, primary, Lubiński, Jan, primary, Cybulski, Cezary, primary, Menkiszak, Janusz, primary, Jensen, Allan, primary, Gayther, Simon A., primary, Ramus, Susan J., primary, Gentry-Maharaj, Aleksandra, primary, Berchuck, Andrew, primary, Wu, Anna H., primary, Pike, Malcolm C., primary, Van Den Berg, David, primary, Terry, Kathryn L., primary, Vitonis, Allison F., primary, Ramirez, Starr M., primary, Rider, David N., primary, Knutson, Keith L., primary, Sellers, Thomas A., primary, Phelan, Catherine M., primary, Doherty, Jennifer A., primary, Johnatty, Sharon E., primary, deFazio, Anna, primary, Song, Honglin, primary, Tyrer, Jonathan, primary, Kalli, Kimberly R., primary, Fridley, Brooke L., primary, Cunningham, Julie M., primary, and Goode, Ellen L., primary

Published
2023
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27. Data from Risk of Ovarian Cancer and the NF-κB Pathway: Genetic Association with IL1A and TNFSF10

Author

Charbonneau, Bridget, primary, Block, Matthew S., primary, Bamlet, William R., primary, Vierkant, Robert A., primary, Kalli, Kimberly R., primary, Fogarty, Zachary, primary, Rider, David N., primary, Sellers, Thomas A., primary, Tworoger, Shelley S., primary, Poole, Elizabeth, primary, Risch, Harvey A., primary, Salvesen, Helga B., primary, Kiemeney, Lambertus A., primary, Baglietto, Laura, primary, Giles, Graham G., primary, Severi, Gianluca, primary, Trabert, Britton, primary, Wentzensen, Nicolas, primary, Chenevix-Trench, Georgia, primary, Whittemore, Alice S., primary, Sieh, Weiva, primary, Chang-Claude, Jenny, primary, Bandera, Elisa V., primary, Orlow, Irene, primary, Terry, Kathryn, primary, Goodman, Marc T., primary, Thompson, Pamela J., primary, Cook, Linda S., primary, Rossing, Mary Anne, primary, Ness, Roberta B., primary, Narod, Steven A., primary, Kupryjanczyk, Jolanta, primary, Lu, Karen, primary, Butzow, Ralf, primary, Dörk, Thilo, primary, Pejovic, Tanja, primary, Campbell, Ian, primary, Le, Nhu D., primary, Bunker, Clareann H., primary, Bogdanova, Natalia, primary, Runnebaum, Ingo B., primary, Eccles, Diana, primary, Paul, James, primary, Wu, Anna H., primary, Gayther, Simon A., primary, Hogdall, Estrid, primary, Heitz, Florian, primary, Kaye, Stanley B., primary, Karlan, Beth Y., primary, Anton-Culver, Hoda, primary, Gronwald, Jacek, primary, Hogdall, Claus K., primary, Lambrechts, Diether, primary, Fasching, Peter A., primary, Menon, Usha, primary, Schildkraut, Joellen, primary, Pearce, Celeste Leigh, primary, Levine, Douglas A., primary, Kjaer, Susanne Kruger, primary, Cramer, Daniel, primary, Flanagan, James M., primary, Phelan, Catherine M., primary, Brown, Robert, primary, Massuger, Leon F.A.G., primary, Song, Honglin, primary, Doherty, Jennifer A., primary, Krakstad, Camilla, primary, Liang, Dong, primary, Odunsi, Kunle, primary, Berchuck, Andrew, primary, Jensen, Allan, primary, Lubiński, Jan, primary, Nevanlinna, Heli, primary, Bean, Yukie T., primary, Lurie, Galina, primary, Ziogas, Argyrios, primary, Walsh, Christine, primary, Despierre, Evelyn, primary, Brinton, Louise, primary, Hein, Alexander, primary, Rudolph, Anja, primary, Dansonka-Mieszkowska, Agnieszka, primary, Olson, Sara H., primary, Harter, Philipp, primary, Tyrer, Jonathan, primary, Vitonis, Allison F., primary, Brooks-Wilson, Angela, primary, Aben, Katja K., primary, Pike, Malcolm C., primary, Ramus, Susan J., primary, Wik, Elisabeth, primary, Cybulski, Cezary, primary, Lin, Jie, primary, Sucheston, Lara, primary, Edwards, Robert, primary, McGuire, Valerie, primary, Lester, Jenny, primary, du Bois, Andreas, primary, Lundvall, Lene, primary, Wang-Gohrke, Shan, primary, Szafron, Lukasz M., primary, Lambrechts, Sandrina, primary, Yang, Hannah, primary, Beckmann, Matthias W., primary, Pelttari, Liisa M., primary, Van Altena, Anne M., primary, van den Berg, David, primary, Halle, Mari K., primary, Gentry-Maharaj, Aleksandra, primary, Schwaab, Ira, primary, Chandran, Urmila, primary, Menkiszak, Janusz, primary, Ekici, Arif B., primary, Wilkens, Lynne R., primary, Leminen, Arto, primary, Modugno, Francesmary, primary, Friel, Grace, primary, Rothstein, Joseph H., primary, Vergote, Ignace, primary, Garcia-Closas, Montserrat, primary, Hildebrandt, Michelle A.T., primary, Sobiczewski, Piotr, primary, Kelemen, Linda E., primary, Pharoah, Paul D.P., primary, Moysich, Kirsten, primary, Knutson, Keith L., primary, Cunningham, Julie M., primary, Fridley, Brooke L., primary, and Goode, Ellen L., primary

Published
2023
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28. Supplementary Tables 1 - 5 from Risk of Ovarian Cancer and the NF-κB Pathway: Genetic Association with IL1A and TNFSF10

Author

Charbonneau, Bridget, primary, Block, Matthew S., primary, Bamlet, William R., primary, Vierkant, Robert A., primary, Kalli, Kimberly R., primary, Fogarty, Zachary, primary, Rider, David N., primary, Sellers, Thomas A., primary, Tworoger, Shelley S., primary, Poole, Elizabeth, primary, Risch, Harvey A., primary, Salvesen, Helga B., primary, Kiemeney, Lambertus A., primary, Baglietto, Laura, primary, Giles, Graham G., primary, Severi, Gianluca, primary, Trabert, Britton, primary, Wentzensen, Nicolas, primary, Chenevix-Trench, Georgia, primary, Whittemore, Alice S., primary, Sieh, Weiva, primary, Chang-Claude, Jenny, primary, Bandera, Elisa V., primary, Orlow, Irene, primary, Terry, Kathryn, primary, Goodman, Marc T., primary, Thompson, Pamela J., primary, Cook, Linda S., primary, Rossing, Mary Anne, primary, Ness, Roberta B., primary, Narod, Steven A., primary, Kupryjanczyk, Jolanta, primary, Lu, Karen, primary, Butzow, Ralf, primary, Dörk, Thilo, primary, Pejovic, Tanja, primary, Campbell, Ian, primary, Le, Nhu D., primary, Bunker, Clareann H., primary, Bogdanova, Natalia, primary, Runnebaum, Ingo B., primary, Eccles, Diana, primary, Paul, James, primary, Wu, Anna H., primary, Gayther, Simon A., primary, Hogdall, Estrid, primary, Heitz, Florian, primary, Kaye, Stanley B., primary, Karlan, Beth Y., primary, Anton-Culver, Hoda, primary, Gronwald, Jacek, primary, Hogdall, Claus K., primary, Lambrechts, Diether, primary, Fasching, Peter A., primary, Menon, Usha, primary, Schildkraut, Joellen, primary, Pearce, Celeste Leigh, primary, Levine, Douglas A., primary, Kjaer, Susanne Kruger, primary, Cramer, Daniel, primary, Flanagan, James M., primary, Phelan, Catherine M., primary, Brown, Robert, primary, Massuger, Leon F.A.G., primary, Song, Honglin, primary, Doherty, Jennifer A., primary, Krakstad, Camilla, primary, Liang, Dong, primary, Odunsi, Kunle, primary, Berchuck, Andrew, primary, Jensen, Allan, primary, Lubiński, Jan, primary, Nevanlinna, Heli, primary, Bean, Yukie T., primary, Lurie, Galina, primary, Ziogas, Argyrios, primary, Walsh, Christine, primary, Despierre, Evelyn, primary, Brinton, Louise, primary, Hein, Alexander, primary, Rudolph, Anja, primary, Dansonka-Mieszkowska, Agnieszka, primary, Olson, Sara H., primary, Harter, Philipp, primary, Tyrer, Jonathan, primary, Vitonis, Allison F., primary, Brooks-Wilson, Angela, primary, Aben, Katja K., primary, Pike, Malcolm C., primary, Ramus, Susan J., primary, Wik, Elisabeth, primary, Cybulski, Cezary, primary, Lin, Jie, primary, Sucheston, Lara, primary, Edwards, Robert, primary, McGuire, Valerie, primary, Lester, Jenny, primary, du Bois, Andreas, primary, Lundvall, Lene, primary, Wang-Gohrke, Shan, primary, Szafron, Lukasz M., primary, Lambrechts, Sandrina, primary, Yang, Hannah, primary, Beckmann, Matthias W., primary, Pelttari, Liisa M., primary, Van Altena, Anne M., primary, van den Berg, David, primary, Halle, Mari K., primary, Gentry-Maharaj, Aleksandra, primary, Schwaab, Ira, primary, Chandran, Urmila, primary, Menkiszak, Janusz, primary, Ekici, Arif B., primary, Wilkens, Lynne R., primary, Leminen, Arto, primary, Modugno, Francesmary, primary, Friel, Grace, primary, Rothstein, Joseph H., primary, Vergote, Ignace, primary, Garcia-Closas, Montserrat, primary, Hildebrandt, Michelle A.T., primary, Sobiczewski, Piotr, primary, Kelemen, Linda E., primary, Pharoah, Paul D.P., primary, Moysich, Kirsten, primary, Knutson, Keith L., primary, Cunningham, Julie M., primary, Fridley, Brooke L., primary, and Goode, Ellen L., primary

Published
2023
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29. 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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31. Ectopic pregnancy treatment by combination therapy

Author

Cymbaluk-Płoska Aneta, Chudecka-Głaz Anita, Kuźniak Sławomir, and Menkiszak Janusz

Subjects
Ectopic pregnancy, Laparoscopy, Hyperosmolar glucose, Methotrexate injection, Medicine
Abstract

Detectability of early stages of ectopic pregnancies has increased due to improvements in ultrasonographic and biochemical techniques. Since the patients’ future procreative plans must be taken into consideration when commencing treatment, the goal of this work was to compare the effects of treatment methods and their impact on fertility. The study included 91 patients treated surgically for ectopic pregnancy. The choice of treatment depended on patients’ general condition, ultrasonographic evaluation and serum level of beta-hCG. A combination of laparoscopic and conservative systemic treatment was applied in 70% of cases. More rapid beta-hCG reduction was noted when laparoscopy and intra-oviductal injection of hyperosmolar glucose or methotrexate (MTX) were combined with intramuscular administration of MTX at a dose of 50 mg/m2. Follow-up examination of 66 patients revealed that the greatest number of spontaneous pregnancies (48%) resulted after this combination therapy. We conclude that this combination treatment is safe and provides satisfactory results in terms of future fertility.

Published
2016
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32. Bilateral Oophorectomy and the Risk of Breast Cancer in BRCA1 Mutation Carriers: a Reappraisal

Author

Kotsopoulos, J, Lubiński, J, Gronwald, J, Menkiszak, J, Mccuaig, J, Metcalfe, K, Foulkes, W, Neuhausen, S, Sun, S, Karlan, B, Eisen, A, Tung, N, Olopade, O, Couch, F, Huzarski, T, Senter, L, Bordeleau, L, Singer, C, Eng, C, Fruscio, R, Pal, T, Sun, P, Narod, S, Kotsopoulos, Joanne, Lubiński, Jan, Gronwald, Jacek, Menkiszak, Janusz, McCuaig, Jeanna, Metcalfe, Kelly, Foulkes, William D, Neuhausen, Susan L, Sun, Sophie, Karlan, Beth Y, Eisen, Andrea, Tung, Nadine, Olopade, Olufunmilayo I, Couch, Fergus J, Huzarski, Tomasz, Senter, Leigha, Bordeleau, Louise, Singer, Christian F, Eng, Charis, Fruscio, Robert, Pal, Tuya, Sun, Ping, Narod, Steven A, Kotsopoulos, J, Lubiński, J, Gronwald, J, Menkiszak, J, Mccuaig, J, Metcalfe, K, Foulkes, W, Neuhausen, S, Sun, S, Karlan, B, Eisen, A, Tung, N, Olopade, O, Couch, F, Huzarski, T, Senter, L, Bordeleau, L, Singer, C, Eng, C, Fruscio, R, Pal, T, Sun, P, Narod, S, Kotsopoulos, Joanne, Lubiński, Jan, Gronwald, Jacek, Menkiszak, Janusz, McCuaig, Jeanna, Metcalfe, Kelly, Foulkes, William D, Neuhausen, Susan L, Sun, Sophie, Karlan, Beth Y, Eisen, Andrea, Tung, Nadine, Olopade, Olufunmilayo I, Couch, Fergus J, Huzarski, Tomasz, Senter, Leigha, Bordeleau, Louise, Singer, Christian F, Eng, Charis, Fruscio, Robert, Pal, Tuya, Sun, Ping, and Narod, Steven A

Abstract

Background: The lack of consensus on whether bilateral oophorectomy impacts risk of developing breast cancer among BRCA1 mutation carriers might be attributed to various biases, specifically, cancer-induced testing bias due to inclusion of prevalent cases. We conducted two complementary matched case-control analyses to evaluate the association of oophorectomy and BRCA1 breast cancer. Methods: A research questionnaire was administered every two years to collect information on exposures and disease. In the first analysis, we limited the study to prevalent breast cancer cases (diagnosed prior to study entry; n = 2,962) who were matched to controls on year of birth and country of residence (n=4,358). In the second approach, we limited to 330 incident cases (diagnosed in the follow-up period) and 1,548 matched controls. Conditional logistic regression was used to estimate the adjusted odds ratios (OR) and 95% confidence intervals (CI) of invasive breast cancer. Results: In the first approach, there was a significant inverse association between oophorectomy and the risk of developing breast cancer [OR = 0.43; 95% confidence interval (CI), 0.34- 0.55; P < 00001]. In the second approach, there was no association between oophorectomy and risk (OR = 1.21; 95% CI, 0.87-1.70; P = 0.26). Conclusions: The inclusion of women with a personal history of breast cancer prior to ascertainment likely impacts upon the association of oophorectomy and BRCA1 breast cancer risk. Impact: Oophorectomy is unlikely a determinant of breast cancer risk in BRCA1 mutation carriers but should be offered at age 35 to reduce the risk of ovarian and fallopian tube cancer.

Published
2022

34. Hereditary breast and ovarian cancer

Author

Gronwald Jacek, Byrski Tomasz, Huzarski Tomasz, Oszurek Oleg, Janicka Anna, Szymańska-Pasternak Jolanta, Górski Bohdan, Menkiszak Janusz, Rzepka-Górska Izabella, and Lubiński Jan

Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282, Genetics, QH426-470
Published
2008
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35. Association of Type and Location of BRCA1 and BRCA2 Mutations With Risk of Breast and Ovarian Cancer

Author

Rebbeck, Timothy R., Mitra, Nandita, Wan, Fei, Sinilnikova, Olga M., Healey, Sue, McGuffog, Lesley, Mazoyer, Sylvie, Chenevix-Trench, Georgia, Easton, Douglas F., Antoniou, Antonis C., Nathanson, Katherine L., Laitman, Yael, Kushnir, Anya, Paluch-Shimon, Shani, Berger, Raanan, Zidan, Jamal, Friedman, Eitan, Ehrencrona, Hans, Stenmark-Askmalm, Marie, Einbeigi, Zakaria, Loman, Niklas, Harbst, Katja, Rantala, Johanna, Melin, Beatrice, Huo, Dezheng, Olopade, Olufunmilayo I., Seldon, Joyce, Ganz, Patricia A., Nussbaum, Robert L., Chan, Salina B., Odunsi, Kunle, Gayther, Simon A., Domchek, Susan M., Arun, Banu K., Lu, Karen H., Mitchell, Gillian, Karlan, Beth Y., Walsh, Christine, Lester, Jenny, Godwin, Andrew K., Pathak, Harsh, Ross, Eric, Daly, Mary B., Whittemore, Alice S., John, Esther M., Miron, Alexander, Terry, Mary Beth, Chung, Wendy K., Goldgar, David E., Buys, Saundra S., Janavičius, Ramūnas, Tihomirova, Laima, Tung, Nadine, Dorfling, Cecilia M., van Rensburg, Elizabeth J., Steele, Linda, Neuhausen, Susan L., Ding, Yuan Chun, Ejlertsen, Bent, Gerdes, Anne-Marie, Hansen, Thomas v. O., Ramón y Cajal, Teresa, Osorio, Ana, Benitez, Javier, Godino, Javier, Tejada, Maria-Isabel, Duran, Mercedes, Weitzel, Jeffrey N., Bobolis, Kristie A, Sand, Sharon R., Fontaine, Annette, Savarese, Antonella, Pasini, Barbara, Peissel, Bernard, Bonanni, Bernardo, Zaffaroni, Daniela, Vignolo-Lutati, Francesca, Scuvera, Giulietta, Giannini, Giuseppe, Bernard, Loris, Genuardi, Maurizio, Radice, Paolo, Dolcetti, Riccardo, Manoukian, Siranoush, Pensotti, Valeria, Gismondi, Viviana, Yannoukakos, Drakoulis, Fostira, Florentia, Garber, Judy, Torres, Diana, Rashid, Muhammad Usman, Hamann, Ute, Peock, Susan, Frost, Debra, Platte, Radka, Evans, D. Gareth, Eeles, Rosalind, Davidson, Rosemarie, Eccles, Diana, Cole, Trevor, Cook, Jackie, Brewer, Carole, Hodgson, Shirley, Morrison, Patrick J., Walker, Lisa, Porteous, Mary E., Kennedy, M. John, Izatt, Louise, Adlard, Julian, Donaldson, Alan, Ellis, Steve, Sharma, Priyanka, Schmutzler, Rita Katharina, Wappenschmidt, Barbara, Becker, Alexandra, Rhiem, Kerstin, Hahnen, Eric, Engel, Christoph, Meindl, Alfons, Engert, Stefanie, Ditsch, Nina, Arnold, Norbert, Plendl, Hans Jörg, Mundhenke, Christoph, Niederacher, Dieter, Fleisch, Markus, Sutter, Christian, Bartram, C. R., Dikow, Nicola, Wang-Gohrke, Shan, Gadzicki, Dorothea, Steinemann, Doris, Kast, Karin, Beer, Marit, Varon-Mateeva, Raymonda, Gehrig, Andrea, Weber, Bernhard H., Stoppa-Lyonnet, Dominique, Sinilnikova, Olga M., Mazoyer, Sylvie, Houdayer, Claude, Belotti, Muriel, Gauthier-Villars, Marion, Damiola, Francesca, Boutry-Kryza, Nadia, Lasset, Christine, Sobol, Hagay, Peyrat, Jean-Philippe, Muller, Danièle, Fricker, Jean-Pierre, Collonge-Rame, Marie-Agnès, Mortemousque, Isabelle, Nogues, Catherine, Rouleau, Etienne, Isaacs, Claudine, De Paepe, Anne, Poppe, Bruce, Claes, Kathleen, De Leeneer, Kim, Piedmonte, Marion, Rodriguez, Gustavo, Wakely, Katie, Boggess, John, Blank, Stephanie V., Basil, Jack, Azodi, Masoud, Phillips, Kelly-Anne, Caldes, Trinidad, de la Hoya, Miguel, Romero, Atocha, Nevanlinna, Heli, Aittomäki, Kristiina, van der Hout, Annemarie H., Hogervorst, Frans B. L., Verhoef, Senno, Collée, J. Margriet, Seynaeve, Caroline, Oosterwijk, Jan C., Gille, Johannes J. P., Wijnen, Juul T., Garcia, Encarna B. Gómez, Kets, Carolien M., Ausems, Margreet G. E. M., Aalfs, Cora M., Devilee, Peter, Mensenkamp, Arjen R., Kwong, Ava, Olah, Edith, Papp, Janos, Diez, Orland, Lazaro, Conxi, Darder, Esther, Blanco, Ignacio, Salinas, Mónica, Jakubowska, Anna, Lubinski, Jan, Gronwald, Jacek, Jaworska-Bieniek, Katarzyna, Durda, Katarzyna, Sukiennicki, Grzegorz, Huzarski, Tomasz, Byrski, Tomasz, Cybulski, Cezary, Toloczko-Grabarek, Aleksandra, Złowocka-Perłowska, Elżbieta, Menkiszak, Janusz, Arason, Adalgeir, Barkardottir, Rosa B., Simard, Jacques, Laframboise, Rachel, Montagna, Marco, Agata, Simona, Alducci, Elisa, Peixoto, Ana, Teixeira, Manuel R., Spurdle, Amanda B., Lee, Min Hyuk, Park, Sue K., Kim, Sung-Won, Friebel, Tara M., Couch, Fergus J., Lindor, Noralane M., Pankratz, Vernon S., Guidugli, Lucia, Wang, Xianshu, Tischkowitz, Marc, Foretova, Lenka, Vijai, Joseph, Offit, Kenneth, Robson, Mark, Rau-Murthy, Rohini, Kauff, Noah, Fink-Retter, Anneliese, Singer, Christian F., Rappaport, Christine, Gschwantler-Kaulich, Daphne, Pfeiler, Georg, Tea, Muy-Kheng, Berger, Andreas, Greene, Mark H., Mai, Phuong L., Imyanitov, Evgeny N., Toland, Amanda Ewart, Senter, Leigha, Bojesen, Anders, Pedersen, Inge Sokilde, Skytte, Anne-Bine, Sunde, Lone, Thomassen, Mads, Moeller, Sanne Traasdahl, Kruse, Torben A., Jensen, Uffe Birk, Caligo, Maria Adelaide, Aretini, Paolo, Teo, Soo-Hwang, Selkirk, Christina G., Hulick, Peter J., and Andrulis, Irene

Published
2015
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38. The presence of prostate cancer at biopsy is predicted by a number of genetic variants

Author

Kashyap, Aniruddh, Kluźniak, Wojciech, Wokołorczyk, Dominika, Gołąb, Adam, Sikorski, Andrzej, Słojewski, Marcin, Gliniewicz, Bartłomiej, Świtała, Jerzy, Borkowski, Tomasz, Borkowski, Andrzej, Antczak, Andrzej, Wojnar, Łukasz, Przybyła, Jacek, Sosnowski, Marek, Małkiewicz, Bartosz, Zdrojowy, Romuald, Sikorska-Radek, Paulina, Matych, Józef, Wilkosz, Jacek, Różański, Waldemar, Kiś, Jacek, Bar, Krzysztof, Bryniarski, Piotr, Paradysz, Andrzej, Jersak, Konrad, Niemirowicz, Jerzy, Słupski, Piotr, Jarzemski, Piotr, Skrzypczyk, Michał, Dobruch, Jakub, Domagała, Paweł, Piotrowski, Krzysztof, Jakubowska, Anna, Gronwald, Jacek, Huzarski, Tomasz, Byrski, Tomasz, Dębniak, Tadeusz, Górski, Bohdan, Masojć, Bartłomiej, van de Wetering, Thierry, Menkiszak, Janusz, Akbari, Mohammad R., Lubiński, Jan, Narod, Steven A., and Cybulski, Cezary

Published
2014
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40. Recurrent Mutations in BRCA1, BRCA2, RAD51C, PALB2 and CHEK2 in Polish Patients with Ovarian Cancer

Author

Łukomska, Alicja, primary, Menkiszak, Janusz, additional, Gronwald, Jacek, additional, Tomiczek-Szwiec, Joanna, additional, Szwiec, Marek, additional, Jasiówka, Marek, additional, Blecharz, Paweł, additional, Kluz, Tomasz, additional, Stawicka-Niełacna, Małgorzata, additional, Mądry, Radosław, additional, Białkowska, Katarzyna, additional, Prajzendanc, Karolina, additional, Kluźniak, Wojciech, additional, Cybulski, Cezary, additional, Dębniak, Tadeusz, additional, Huzarski, Tomasz, additional, Tołoczko-Grabarek, Aleksandra, additional, Byrski, Tomasz, additional, Baszuk, Piotr, additional, Narod, Steven A., additional, Lubiński, Jan, additional, and Jakubowska, Anna, additional

Published
2021
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48. Ovarian cancer risk in Polish BRCA1 mutation carriers is not associated with the prohibitin 3' untranslated region polymorphism

Author

Benner Axel, Byrski Tomasz, Huzarski Tomasz, Górski Bohdan, Menkiszak Janusz, Gronwald Jacek, Jakubowska Anna, Lubiński Jan, Scott Rodney J, and Hamann Ute

Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract Background The variable penetrance of ovarian cancer in BRCA1 mutation carriers suggests that other genetic or environmental factors modify disease risk. The C to T transition in the 3' untranslated region of the prohibitin (PHB) gene alters mRNA function and has recently been shown to be associated with hereditary breast cancer risk in Polish women harbouring BRCA1 mutations. Methods To investigate whether the PHB 3'UTR polymorphism also modifies hereditary ovarian cancer risk, we performed a case-control study among Polish women carrying one of the three common founder mutations (5382insC, 300 T > G, 4154delA) including 127 ovarian cases and 127 unaffected controls who had both breasts and ovaries intact. Controls were matched to cases by year of birth and BRCA1 mutation. Genotyping analysis was performed using PCR-based restriction fragment length polymorphism analysis. Odds ratios (OR) were calculated using conditional and penalized univariable and multivariable logistic regression. Results A comparison of the genotype frequencies between cases and controls revealed no association of the PHB 3'UTR _CT+TT genotypes with ovarian cancer risk (ORadj 1.34; 95% CI, 0.59–3.11). Conclusion Our data suggest that the PHB 3'UTR polymorphism does not modify ovarian cancer risk in women carrying one of the three Polish BRCA1 founder mutations.

Published
2008
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49. Evaluation of biologically active substances promoting the development of or protecting against endometrial cancer

Author

Cymbaluk-Płoska,Aneta, Chudecka-Głaz,Anita, Jagodzińska,Anna, Pius-Sadowska,Ewa, Sompolska-Rzechuła,Agnieszka, Machaliński,Bogusław, Menkiszak,Janusz, Cymbaluk-Płoska,Aneta, Chudecka-Głaz,Anita, Jagodzińska,Anna, Pius-Sadowska,Ewa, Sompolska-Rzechuła,Agnieszka, Machaliński,Bogusław, and Menkiszak,Janusz

Abstract

Aneta Cymbaluk-PÅ‚oska,1 Anita Chudecka-GÅ‚az,1 Anna JagodziÅ„ska,1 Ewa Pius-Sadowska,2 Agnieszka Sompolska-RzechuÅ‚a,3 BogusÅ‚aw MachaliÅ„ski,2 Janusz Menkiszak1 1Department of Gynecological Surgery and Gynecological Oncology of Adults and Adolescents, Pomeranian Medical University, Szczecin, Poland; 2General Pathology Department, Pomeranian Medical University, Szczecin, Poland; 3Department of Statistics, West Pomeranian University of Technology, Szczecin, Poland Introduction: Adipose tissue is considered an endocrine organ and produces a number of biologically active substances. Aims: To consider the role that four adipokines – leptin, omentin-1, vaspin, and galectin-3 – play in the diagnosis of endometrium cancer and to investigate the association between serum concentrations of adipose tissue metabolism products and the diagnostics and prognosis in endometrial cancer. Patients and methods: The study included 168 patients with body mass index (BMI) >20 kg/m2 admitted due to post-menopausal bleeding. Results: A receiver operating characteristic curves test was performed to determine the diagnostic values of the proteins tested. For leptin and galectin-3 the area under the curve (AUC) values were 0.79/0.68, while for vaspin and omentin-1 the AUC values were 0.82/0.86 for all study patients. The final model identified the following independent risk factors: glucose concentration, BMI, waist circumference, leptin, and vaspin concentrations. Diagnostic values of leptin and galectin-3 with regard to differentiation between high (Fédération Internationale de Gynécologie Obstétrique [FIGO] III and IV) and low (FIGO I and II) stages of clinical tumor advancement and prediction of tumor grading (G1 vs G3) based on the AUC curve were 0.82/0.70 and 0.80/0.74. The AUC values for vaspin and omentin-1 with respect to differentiation between histopathological advancement and grading were 0.86/0.81 and 0.83/0.

Published
2018

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