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171 results on '"Schmutzler, Rita Katharina"'

1. First international workshop of the ATM and cancer risk group (4-5 December 2019)

Author: Lesueur, Fabienne, Easton, Douglas F., Renault, Anne-Laure, Tavtigian, Sean V., Bernstein, Jonine L., Kote-Jarai, Zsofia, Eeles, Rosalind A., Plaseska-Karanfia, Dijana, Feliubadaló, Lidia, Arun, Banu, Herold, Natalie, Versmold, Beatrix, Schmutzler, Rita Katharina, Nguyen-Dumont, Tú, Southey, Melissa C., Dorling, Leila, Dunning, Alison M., Ghiorzo, Paola, Dalmasso, Bruna Samia, Cavaciuti, Eve, Le Gal, Dorothée, Roberts, Nicholas J., Dominguez-Valentin, Mev, Rookus, Matti, Taylor, Alexander M. R., Goldstein, Alisa M., Goldgar, David E., Stoppa-Lyonnet, Dominique, and Andrieu, Nadine
Published: 2022
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2. Risk-Adjusted Prevention. Perspectives on the Governance of Entitlements to Benefits in the Case of Genetic (Breast Cancer) Risks

Author: Meier, Friedhelm, Harney, Anke, Rhiem, Kerstin, Neusser, Silke, Neumann, Anja, Braun, Matthias, Wasem, Jürgen, Huster, Stefan, Dabrock, Peter, Schmutzler, Rita Katharina, Krämer, Alwin, Series Editor, Lu, Jiade J., Series Editor, Bauer, Axel W., editor, Hofheinz, Ralf-Dieter, editor, and Utikal, Jochen S., editor
Published: 2021
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3. Implementing mainstream genetic counseling within the area‐wide network of the German Consortium Hereditary Breast and Ovarian Cancer (GD‐HBOC): Satisfaction of primary care providers with the provided state‐of‐the‐art training by the Cologne Center

Author: Herold, Natalie, primary, Bredow, Kathrin, additional, Ernst, Corinna, additional, Tüchler, Anja, additional, Blümcke, Britta, additional, Waha, Anke, additional, Keser, Ebru, additional, Hauke, Jan, additional, Wappenschmidt, Barbara, additional, Hahnen, Eric, additional, Schmutzler, Rita Katharina, additional, and Rhiem, Kerstin, additional
Published: 2024
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4. Risikoadaptierte Prävention bei familiär bedingtem Brust- und Eierstockkrebs: Ein Best-Practice-Beispiel

Author: Schmutzler, Rita Katharina
Published: 2021
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5. Identification of six new susceptibility loci for invasive epithelial ovarian cancer.

Author: Kuchenbaecker, Karoline B, Ramus, Susan J, Tyrer, Jonathan, Lee, Andrew, Shen, Howard C, Beesley, Jonathan, Lawrenson, Kate, McGuffog, Lesley, Healey, Sue, Lee, Janet M, Spindler, Tassja J, Lin, Yvonne G, Pejovic, Tanja, Bean, Yukie, Li, Qiyuan, Coetzee, Simon, Hazelett, Dennis, Miron, Alexander, Southey, Melissa, Terry, Mary Beth, Goldgar, David E, Buys, Saundra S, Janavicius, Ramunas, Dorfling, Cecilia M, van Rensburg, Elizabeth J, Neuhausen, Susan L, Ding, Yuan Chun, Hansen, Thomas VO, Jønson, Lars, Gerdes, Anne-Marie, Ejlertsen, Bent, Barrowdale, Daniel, Dennis, Joe, Benitez, Javier, Osorio, Ana, Garcia, Maria Jose, Komenaka, Ian, Weitzel, Jeffrey N, Ganschow, Pamela, Peterlongo, Paolo, Bernard, Loris, Viel, Alessandra, Bonanni, Bernardo, Peissel, Bernard, Manoukian, Siranoush, Radice, Paolo, Papi, Laura, Ottini, Laura, Fostira, Florentia, Konstantopoulou, Irene, Garber, Judy, Frost, Debra, Perkins, Jo, Platte, Radka, Ellis, Steve, EMBRACE, Godwin, Andrew K, Schmutzler, Rita Katharina, Meindl, Alfons, Engel, Christoph, Sutter, Christian, Sinilnikova, Olga M, GEMO Study Collaborators, Damiola, Francesca, Mazoyer, Sylvie, Stoppa-Lyonnet, Dominique, Claes, Kathleen, De Leeneer, Kim, Kirk, Judy, Rodriguez, Gustavo C, Piedmonte, Marion, O'Malley, David M, de la Hoya, Miguel, Caldes, Trinidad, Aittomäki, Kristiina, Nevanlinna, Heli, Collée, J Margriet, Rookus, Matti A, Oosterwijk, Jan C, Breast Cancer Family Registry, Tihomirova, Laima, Tung, Nadine, Hamann, Ute, Isaccs, Claudine, Tischkowitz, Marc, Imyanitov, Evgeny N, Caligo, Maria A, Campbell, Ian G, Hogervorst, Frans BL, HEBON, Olah, Edith, Diez, Orland, Blanco, Ignacio, Brunet, Joan, Lazaro, Conxi, Pujana, Miquel Angel, Jakubowska, Anna, Gronwald, Jacek, Lubinski, Jan, and Sukiennicki, Grzegorz
Subjects: EMBRACE, GEMO Study Collaborators, Breast Cancer Family Registry, HEBON, KConFab Investigators, Australian Cancer Study, Australian Ovarian Cancer Study Group, Consortium of Investigators of Modifiers of BRCA1 and BRCA2, Humans, Neoplasms, Glandular and Epithelial, Ovarian Neoplasms, Genetic Predisposition to Disease, BRCA1 Protein, BRCA2 Protein, Risk, Genotype, Heterozygote, Mutation, Polymorphism, Single Nucleotide, Alleles, Genes, Reporter, Quantitative Trait Loci, Adolescent, Adult, Female, Genome-Wide Association Study, Young Adult, Carcinoma, Ovarian Epithelial, Human Genome, Rare Diseases, Genetics, Cancer, Prevention, Ovarian Cancer, 2.1 Biological and endogenous factors, Aetiology, Biological Sciences, Medical and Health Sciences, Developmental Biology
Abstract: Genome-wide association studies (GWAS) have identified 12 epithelial ovarian cancer (EOC) susceptibility alleles. The pattern of association at these loci is consistent in BRCA1 and BRCA2 mutation carriers who are at high risk of EOC. After imputation to 1000 Genomes Project data, we assessed associations of 11 million genetic variants with EOC risk from 15,437 cases unselected for family history and 30,845 controls and from 15,252 BRCA1 mutation carriers and 8,211 BRCA2 mutation carriers (3,096 with ovarian cancer), and we combined the results in a meta-analysis. This new study design yielded increased statistical power, leading to the discovery of six new EOC susceptibility loci. Variants at 1p36 (nearest gene, WNT4), 4q26 (SYNPO2), 9q34.2 (ABO) and 17q11.2 (ATAD5) were associated with EOC risk, and at 1p34.3 (RSPO1) and 6p22.1 (GPX6) variants were specifically associated with the serous EOC subtype, all with P < 5 × 10(-8). Incorporating these variants into risk assessment tools will improve clinical risk predictions for BRCA1 and BRCA2 mutation carriers.
Published: 2015

6. Refined histopathological predictors of BRCA1 and BRCA2mutation status: a large-scale analysis of breast cancer characteristics from the BCAC, CIMBA, and ENIGMA consortia

Author: Spurdle, Amanda B, Couch, Fergus J, Parsons, Michael T, McGuffog, Lesley, Barrowdale, Daniel, Bolla, Manjeet K, Wang, Qin, Healey, Sue, Schmutzler, Rita Katharina, Wappenschmidt, Barbara, Rhiem, Kerstin, Hahnen, Eric, Engel, Christoph, Meindl, Alfons, Ditsch, Nina, Arnold, Norbert, Plendl, Hansjoerg, Niederacher, Dieter, Sutter, Christian, Wang-Gohrke, Shan, Steinemann, Doris, Preisler-Adams, Sabine, Kast, Karin, Varon-Mateeva, Raymonda, Ellis, Steve, Frost, Debra, Platte, Radka, Perkins, Jo, Evans, D Gareth, Izatt, Louise, Eeles, Ros, Adlard, Julian, Davidson, Rosemarie, Cole, Trevor, Scuvera, Giulietta, Manoukian, Siranoush, Bonanni, Bernardo, Mariette, Frederique, Fortuzzi, Stefano, Viel, Alessandra, Pasini, Barbara, Papi, Laura, Varesco, Liliana, Balleine, Rosemary, Nathanson, Katherine L, Domchek, Susan M, Offitt, Kenneth, Jakubowska, Anna, Lindor, Noralane, Thomassen, Mads, Jensen, Uffe Birk, Rantala, Johanna, Borg, Åke, Andrulis, Irene L, Miron, Alexander, Hansen, Thomas VO, Caldes, Trinidad, Neuhausen, Susan L, Toland, Amanda E, Nevanlinna, Heli, Montagna, Marco, Garber, Judy, Godwin, Andrew K, Osorio, Ana, Factor, Rachel E, Terry, Mary B, Rebbeck, Timothy R, Karlan, Beth Y, Southey, Melissa, Rashid, Muhammad Usman, Tung, Nadine, Pharoah, Paul DP, Blows, Fiona M, Dunning, Alison M, Provenzano, Elena, Hall, Per, Czene, Kamila, Schmidt, Marjanka K, Broeks, Annegien, Cornelissen, Sten, Verhoef, Senno, Fasching, Peter A, Beckmann, Matthias W, Ekici, Arif B, Slamon, Dennis J, Bojesen, Stig E, Nordestgaard, Børge G, Nielsen, Sune F, Flyger, Henrik, Chang-Claude, Jenny, Flesch-Janys, Dieter, Rudolph, Anja, Seibold, Petra, Aittomäki, Kristiina, Muranen, Taru A, Heikkilä, Päivi, Blomqvist, Carl, Figueroa, Jonine, Chanock, Stephen J, and Brinton, Louise
Subjects: Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Breast Cancer, Cancer, Prevention, Genetics, Detection, screening and diagnosis, 4.2 Evaluation of markers and technologies, Adult, Age Factors, Aged, Breast Neoplasms, Carcinoma, Female, Genes, BRCA1, Genes, BRCA2, Humans, Likelihood Functions, Middle Aged, Mutation, Neoplasm Grading, Neoplasm Staging, Receptor, ErbB-2, Receptors, Estrogen, Receptors, Progesterone, Triple Negative Breast Neoplasms, ABCTB Investigators, EMBRACE Group, GENICA Network, HEBON Group, kConFab Investigators, Receptor, erbB-2, Oncology & Carcinogenesis, Oncology and carcinogenesis
Abstract: The distribution of histopathological features of invasive breast tumors in BRCA1 or BRCA2 germline mutation carriers differs from that of individuals with no known mutation. Histopathological features thus have utility for mutation prediction, including statistical modeling to assess pathogenicity of BRCA1 or BRCA2 variants of uncertain clinical significance. We analyzed large pathology datasets accrued by the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) and the Breast Cancer Association Consortium (BCAC) to reassess histopathological predictors of BRCA1 and BRCA2 mutation status, and provide robust likelihood ratio (LR) estimates for statistical modeling. Selection criteria for study/center inclusion were estrogen receptor (ER) status or grade data available for invasive breast cancer diagnosed younger than 70 years. The dataset included 4,477 BRCA1 mutation carriers, 2,565 BRCA2 mutation carriers, and 47,565 BCAC breast cancer cases. Country-stratified estimates of the likelihood of mutation status by histopathological markers were derived using a Mantel-Haenszel approach. ER-positive phenotype negatively predicted BRCA1 mutation status, irrespective of grade (LRs from 0.08 to 0.90). ER-negative grade 3 histopathology was more predictive of positive BRCA1 mutation status in women 50 years or older (LR = 4.13 (3.70 to 4.62)) versus younger than 50 years (LR = 3.16 (2.96 to 3.37)). For BRCA2, ER-positive grade 3 phenotype modestly predicted positive mutation status irrespective of age (LR = 1.7-fold), whereas ER-negative grade 3 features modestly predicted positive mutation status at 50 years or older (LR = 1.54 (1.27 to 1.88)). Triple-negative tumor status was highly predictive of BRCA1 mutation status for women younger than 50 years (LR = 3.73 (3.43 to 4.05)) and 50 years or older (LR = 4.41 (3.86 to 5.04)), and modestly predictive of positive BRCA2 mutation status in women 50 years or older (LR = 1.79 (1.42 to 2.24)). These results refine likelihood-ratio estimates for predicting BRCA1 and BRCA2 mutation status by using commonly measured histopathological features. Age at diagnosis is an important variable for most analyses, and grade is more informative than ER status for BRCA2 mutation carrier prediction. The estimates will improve BRCA1 and BRCA2 variant classification and inform patient mutation testing and clinical management.
Published: 2014

7. Risk-Adjusted Prevention. Perspectives on the Governance of Entitlements to Benefits in the Case of Genetic (Breast Cancer) Risks

Author: Meier, Friedhelm, primary, Harney, Anke, additional, Rhiem, Kerstin, additional, Neusser, Silke, additional, Neumann, Anja, additional, Braun, Matthias, additional, Wasem, Jürgen, additional, Huster, Stefan, additional, Dabrock, Peter, additional, and Schmutzler, Rita Katharina, additional
Published: 2021
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8. DNA glycosylases involved in base excision repair may be associated with cancer risk in BRCA1 and BRCA2 mutation carriers.

Author: Osorio, Ana, Milne, Roger L, Kuchenbaecker, Karoline, Vaclová, Tereza, Pita, Guillermo, Alonso, Rosario, Peterlongo, Paolo, Blanco, Ignacio, de la Hoya, Miguel, Duran, Mercedes, Díez, Orland, Ramón Y Cajal, Teresa, Konstantopoulou, Irene, Martínez-Bouzas, Cristina, Andrés Conejero, Raquel, Soucy, Penny, McGuffog, Lesley, Barrowdale, Daniel, Lee, Andrew, SWE-BRCA, Arver, Brita, Rantala, Johanna, Loman, Niklas, Ehrencrona, Hans, Olopade, Olufunmilayo I, Beattie, Mary S, Domchek, Susan M, Nathanson, Katherine, Rebbeck, Timothy R, Arun, Banu K, Karlan, Beth Y, Walsh, Christine, Lester, Jenny, John, Esther M, Whittemore, Alice S, Daly, Mary B, Southey, Melissa, Hopper, John, Terry, Mary B, Buys, Saundra S, Janavicius, Ramunas, Dorfling, Cecilia M, van Rensburg, Elizabeth J, Steele, Linda, Neuhausen, Susan L, Ding, Yuan Chun, Hansen, Thomas VO, Jønson, Lars, Ejlertsen, Bent, Gerdes, Anne-Marie, Infante, Mar, Herráez, Belén, Moreno, Leticia Thais, Weitzel, Jeffrey N, Herzog, Josef, Weeman, Kisa, Manoukian, Siranoush, Peissel, Bernard, Zaffaroni, Daniela, Scuvera, Giulietta, Bonanni, Bernardo, Mariette, Frederique, Volorio, Sara, Viel, Alessandra, Varesco, Liliana, Papi, Laura, Ottini, Laura, Tibiletti, Maria Grazia, Radice, Paolo, Yannoukakos, Drakoulis, Garber, Judy, Ellis, Steve, Frost, Debra, Platte, Radka, Fineberg, Elena, Evans, Gareth, Lalloo, Fiona, Izatt, Louise, Eeles, Ros, Adlard, Julian, Davidson, Rosemarie, Cole, Trevor, Eccles, Diana, Cook, Jackie, Hodgson, Shirley, Brewer, Carole, Tischkowitz, Marc, Douglas, Fiona, Porteous, Mary, Side, Lucy, Walker, Lisa, Morrison, Patrick, Donaldson, Alan, Kennedy, John, Foo, Claire, Godwin, Andrew K, Schmutzler, Rita Katharina, Wappenschmidt, Barbara, Rhiem, Kerstin, and Engel, Christoph
Subjects: SWE-BRCA, HEBON, KConFab Investigators, Humans, Breast Neoplasms, Ovarian Neoplasms, Genetic Predisposition to Disease, DNA Glycosylases, BRCA1 Protein, BRCA2 Protein, Risk, DNA Repair, Genotype, Polymorphism, Single Nucleotide, Adolescent, Adult, Aged, Aged, 80 and over, Middle Aged, Female, Polymorphism, Single Nucleotide, and over, Developmental Biology, Genetics
Abstract: Single Nucleotide Polymorphisms (SNPs) in genes involved in the DNA Base Excision Repair (BER) pathway could be associated with cancer risk in carriers of mutations in the high-penetrance susceptibility genes BRCA1 and BRCA2, given the relation of synthetic lethality that exists between one of the components of the BER pathway, PARP1 (poly ADP ribose polymerase), and both BRCA1 and BRCA2. In the present study, we have performed a comprehensive analysis of 18 genes involved in BER using a tagging SNP approach in a large series of BRCA1 and BRCA2 mutation carriers. 144 SNPs were analyzed in a two stage study involving 23,463 carriers from the CIMBA consortium (the Consortium of Investigators of Modifiers of BRCA1 and BRCA2). Eleven SNPs showed evidence of association with breast and/or ovarian cancer at p
Published: 2014

9. Genome-wide association study in BRCA1 mutation carriers identifies novel loci associated with breast and ovarian cancer risk.

Author: Couch, Fergus J, Wang, Xianshu, McGuffog, Lesley, Lee, Andrew, Olswold, Curtis, Kuchenbaecker, Karoline B, Soucy, Penny, Fredericksen, Zachary, Barrowdale, Daniel, Dennis, Joe, Gaudet, Mia M, Dicks, Ed, Kosel, Matthew, Healey, Sue, Sinilnikova, Olga M, Lee, Adam, Bacot, François, Vincent, Daniel, Hogervorst, Frans BL, Peock, Susan, Stoppa-Lyonnet, Dominique, Jakubowska, Anna, kConFab Investigators, Radice, Paolo, Schmutzler, Rita Katharina, SWE-BRCA, Domchek, Susan M, Piedmonte, Marion, Singer, Christian F, Friedman, Eitan, Thomassen, Mads, Ontario Cancer Genetics Network, Hansen, Thomas VO, Neuhausen, Susan L, Szabo, Csilla I, Blanco, Ignacio, Greene, Mark H, Karlan, Beth Y, Garber, Judy, Phelan, Catherine M, Weitzel, Jeffrey N, Montagna, Marco, Olah, Edith, Andrulis, Irene L, Godwin, Andrew K, Yannoukakos, Drakoulis, Goldgar, David E, Caldes, Trinidad, Nevanlinna, Heli, Osorio, Ana, Terry, Mary Beth, Daly, Mary B, van Rensburg, Elizabeth J, Hamann, Ute, Ramus, Susan J, Toland, Amanda Ewart, Caligo, Maria A, Olopade, Olufunmilayo I, Tung, Nadine, Claes, Kathleen, Beattie, Mary S, Southey, Melissa C, Imyanitov, Evgeny N, Tischkowitz, Marc, Janavicius, Ramunas, John, Esther M, Kwong, Ava, Diez, Orland, Balmaña, Judith, Barkardottir, Rosa B, Arun, Banu K, Rennert, Gad, Teo, Soo-Hwang, Ganz, Patricia A, Campbell, Ian, van der Hout, Annemarie H, van Deurzen, Carolien HM, Seynaeve, Caroline, Gómez Garcia, Encarna B, van Leeuwen, Flora E, Meijers-Heijboer, Hanne EJ, Gille, Johannes JP, Ausems, Margreet GEM, Blok, Marinus J, Ligtenberg, Marjolijn JL, Rookus, Matti A, Devilee, Peter, Verhoef, Senno, van Os, Theo AM, Wijnen, Juul T, HEBON, EMBRACE, Frost, Debra, Ellis, Steve, Fineberg, Elena, Platte, Radka, Evans, D Gareth, Izatt, Louise, Eeles, Rosalind A, and Adlard, Julian
Subjects: kConFab Investigators, SWE-BRCA, Ontario Cancer Genetics Network, HEBON, EMBRACE, GEMO Study Collaborators, BCFR, CIMBA, Humans, Breast Neoplasms, Ovarian Neoplasms, Genetic Predisposition to Disease, BRCA1 Protein, BRCA2 Protein, Prognosis, Risk Factors, Genotype, Heterozygote, Mutation, Polymorphism, Single Nucleotide, Middle Aged, Female, Genome-Wide Association Study, Polymorphism, Single Nucleotide, Developmental Biology, Genetics
Abstract: BRCA1-associated breast and ovarian cancer risks can be modified by common genetic variants. To identify further cancer risk-modifying loci, we performed a multi-stage GWAS of 11,705 BRCA1 carriers (of whom 5,920 were diagnosed with breast and 1,839 were diagnosed with ovarian cancer), with a further replication in an additional sample of 2,646 BRCA1 carriers. We identified a novel breast cancer risk modifier locus at 1q32 for BRCA1 carriers (rs2290854, P = 2.7 × 10(-8), HR = 1.14, 95% CI: 1.09-1.20). In addition, we identified two novel ovarian cancer risk modifier loci: 17q21.31 (rs17631303, P = 1.4 × 10(-8), HR = 1.27, 95% CI: 1.17-1.38) and 4q32.3 (rs4691139, P = 3.4 × 10(-8), HR = 1.20, 95% CI: 1.17-1.38). The 4q32.3 locus was not associated with ovarian cancer risk in the general population or BRCA2 carriers, suggesting a BRCA1-specific association. The 17q21.31 locus was also associated with ovarian cancer risk in 8,211 BRCA2 carriers (P = 2×10(-4)). These loci may lead to an improved understanding of the etiology of breast and ovarian tumors in BRCA1 carriers. Based on the joint distribution of the known BRCA1 breast cancer risk-modifying loci, we estimated that the breast cancer lifetime risks for the 5% of BRCA1 carriers at lowest risk are 28%-50% compared to 81%-100% for the 5% at highest risk. Similarly, based on the known ovarian cancer risk-modifying loci, the 5% of BRCA1 carriers at lowest risk have an estimated lifetime risk of developing ovarian cancer of 28% or lower, whereas the 5% at highest risk will have a risk of 63% or higher. Such differences in risk may have important implications for risk prediction and clinical management for BRCA1 carriers.
Published: 2013

10. Identification of 12 new susceptibility loci for different histotypes of epithelial ovarian cancer

Author: Phelan, Catherine M, Kuchenbaecker, Karoline B, Tyrer, Jonathan P, Kar, Siddhartha P, Lawrenson, Kate, Winham, Stacey J, Dennis, Joe, Pirie, Ailith, Riggan, Marjorie J, Chornokur, Ganna, Earp, Madalene A, Lyra, Jr, Paulo C, Lee, Janet M, Coetzee, Simon, Beesley, Jonathan, McGuffog, Lesley, Soucy, Penny, Dicks, Ed, Lee, Andrew, Barrowdale, Daniel, Lecarpentier, Julie, Leslie, Goska, Aalfs, Cora M, Aben, Katja K H, Adams, Marcia, Adlard, Julian, Andrulis, Irene L, Anton-Culver, Hoda, Antonenkova, Natalia, Aravantinos, Gerasimos, Arnold, Norbert, Arun, Banu K, Arver, Brita, Azzollini, Jacopo, Balmaña, Judith, Banerjee, Susana N, Barjhoux, Laure, Barkardottir, Rosa B, Bean, Yukie, Beckmann, Matthias W, Beeghly-Fadiel, Alicia, Benitez, Javier, Bermisheva, Marina, Bernardini, Marcus Q, Birrer, Michael J, Bjorge, Line, Black, Amanda, Blankstein, Kenneth, Blok, Marinus J, Bodelon, Clara, Bogdanova, Natalia, Bojesen, Anders, Bonanni, Bernardo, Borg, Åke, Bradbury, Angela R, Brenton, James D, Brewer, Carole, Brinton, Louise, Broberg, Per, Brooks-Wilson, Angela, Bruinsma, Fiona, Brunet, Joan, Buecher, Bruno, Butzow, Ralf, Buys, Saundra S, Caldes, Trinidad, Caligo, Maria A, Campbell, Ian, Cannioto, Rikki, Carney, Michael E, Cescon, Terence, Chan, Salina B, Chang-Claude, Jenny, Chanock, Stephen, Chen, Xiao Qing, Chiew, Yoke-Eng, Chiquette, Jocelyne, Chung, Wendy K, Claes, Kathleen B M, Conner, Thomas, Cook, Linda S, Cook, Jackie, Cramer, Daniel W, Cunningham, Julie M, D'Aloisio, Aimee A, Daly, Mary B, Damiola, Francesca, Damirovna, Sakaeva Dina, Dansonka-Mieszkowska, Agnieszka, Dao, Fanny, Davidson, Rosemarie, DeFazio, Anna, Delnatte, Capucine, Doheny, Kimberly F, Diez, Orland, Ding, Yuan Chun, Doherty, Jennifer Anne, Domchek, Susan M, Dorfling, Cecilia M, Dörk, Thilo, Dossus, Laure, Duran, Mercedes, Dürst, Matthias, Dworniczak, Bernd, Eccles, Diana, Edwards, Todd, Eeles, Ros, Eilber, Ursula, Ejlertsen, Bent, Ekici, Arif B, Ellis, Steve, Elvira, Mingajeva, Eng, Kevin H, Engel, Christoph, Evans, D Gareth, Fasching, Peter A, Ferguson, Sarah, Ferrer, Sandra Fert, Flanagan, James M, Fogarty, Zachary C, Fortner, Renée T, Fostira, Florentia, Foulkes, William D, Fountzilas, George, Fridley, Brooke L, Friebel, Tara M, Friedman, Eitan, Frost, Debra, Ganz, Patricia A, Garber, Judy, García, María J, Garcia-Barberan, Vanesa, Gehrig, Andrea, Gentry-Maharaj, Aleksandra, Gerdes, Anne-Marie, Giles, Graham G, Glasspool, Rosalind, Glendon, Gord, Godwin, Andrew K, Goldgar, David E, Goranova, Teodora, Gore, Martin, Greene, Mark H, Gronwald, Jacek, Gruber, Stephen, Hahnen, Eric, Haiman, Christopher A, Håkansson, Niclas, Hamann, Ute, Hansen, Thomas V O, Harrington, Patricia A, Harris, Holly R, Hauke, Jan, Hein, Alexander, Henderson, Alex, Hildebrandt, Michelle A T, Hillemanns, Peter, Hodgson, Shirley, Høgdall, Claus K, Høgdall, Estrid, Hogervorst, Frans B L, Holland, Helene, Hooning, Maartje J, Hosking, Karen, Huang, Ruea-Yea, Hulick, Peter J, Hung, Jillian, Hunter, David J, Huntsman, David G, Huzarski, Tomasz, Imyanitov, Evgeny N, Isaacs, Claudine, Iversen, Edwin S, Izatt, Louise, Izquierdo, Angel, Jakubowska, Anna, James, Paul, Janavicius, Ramunas, Jernetz, Mats, Jensen, Allan, Jensen, Uffe Birk, John, Esther M, Johnatty, Sharon, Jones, Michael E, Kannisto, Päivi, Karlan, Beth Y, Karnezis, Anthony, Kast, Karin, Kennedy, Catherine J, Khusnutdinova, Elza, Kiemeney, Lambertus A, Kiiski, Johanna I, Kim, Sung-Won, Kjaer, Susanne K, Köbel, Martin, Kopperud, Reidun K, Kruse, Torben A, Kupryjanczyk, Jolanta, Kwong, Ava, Laitman, Yael, Lambrechts, Diether, Larrañaga, Nerea, Larson, Melissa C, Lazaro, Conxi, Le, Nhu D, Le Marchand, Loic, Lee, Jong Won, Lele, Shashikant B, Leminen, Arto, Leroux, Dominique, Lester, Jenny, Lesueur, Fabienne, Levine, Douglas A, Liang, Dong, Liebrich, Clemens, Lilyquist, Jenna, Lipworth, Loren, Lissowska, Jolanta, Lu, Karen H, Lubinński, Jan, Luccarini, Craig, Lundvall, Lene, Mai, Phuong L, Mendoza-Fandiño, Gustavo, Manoukian, Siranoush, Massuger, Leon F A G, May, Taymaa, Mazoyer, Sylvie, McAlpine, Jessica N, McGuire, Valerie, McLaughlin, John R, McNeish, Iain, Meijers-Heijboer, Hanne, Meindl, Alfons, Menon, Usha, Mensenkamp, Arjen R, Merritt, Melissa A, Milne, Roger L, Mitchell, Gillian, Modugno, Francesmary, Moes-Sosnowska, Joanna, Moffitt, Melissa, Montagna, Marco, Moysich, Kirsten B, Mulligan, Anna Marie, Musinsky, Jacob, Nathanson, Katherine L, Nedergaard, Lotte, Ness, Roberta B, Neuhausen, Susan L, Nevanlinna, Heli, Niederacher, Dieter, Nussbaum, Robert L, Odunsi, Kunle, Olah, Edith, Olopade, Olufunmilayo I, Olsson, Håkan, Olswold, Curtis, O'Malley, David M, Ong, Kai-ren, Onland-Moret, N Charlotte, Orr, Nicholas, Orsulic, Sandra, Osorio, Ana, Palli, Domenico, Papi, Laura, Park-Simon, Tjoung-Won, Paul, James, Pearce, Celeste L, Pedersen, Inge Søkilde, Peeters, Petra H M, Peissel, Bernard, Peixoto, Ana, Pejovic, Tanja, Pelttari, Liisa M, Permuth, Jennifer B, Peterlongo, Paolo, Pezzani, Lidia, Pfeiler, Georg, Phillips, Kelly-Anne, Piedmonte, Marion, Pike, Malcolm C, Piskorz, Anna M, Poblete, Samantha R, Pocza, Timea, Poole, Elizabeth M, Poppe, Bruce, Porteous, Mary E, Prieur, Fabienne, Prokofyeva, Darya, Pugh, Elizabeth, Pujana, Miquel Angel, Pujol, Pascal, Radice, Paolo, Rantala, Johanna, Rappaport-Fuerhauser, Christine, Rennert, Gad, Rhiem, Kerstin, Rice, Patricia, Richardson, Andrea, Robson, Mark, Rodriguez, Gustavo C, Rodríguez-Antona, Cristina, Romm, Jane, Rookus, Matti A, Rossing, Mary Anne, Rothstein, Joseph H, Rudolph, Anja, Runnebaum, Ingo B, Salvesen, Helga B, Sandler, Dale P, Schoemaker, Minouk J, Senter, Leigha, Setiawan, V Wendy, Severi, Gianluca, Sharma, Priyanka, Shelford, Tameka, Siddiqui, Nadeem, Side, Lucy E, Sieh, Weiva, Singer, Christian F, Sobol, Hagay, Song, Honglin, Southey, Melissa C, Spurdle, Amanda B, Stadler, Zsofia, Steinemann, Doris, Stoppa-Lyonnet, Dominique, Sucheston-Campbell, Lara E, Sukiennicki, Grzegorz, Sutphen, Rebecca, Sutter, Christian, Swerdlow, Anthony J, Szabo, Csilla I, Szafron, Lukasz, Tan, Yen Y, Taylor, Jack A, Tea, Muy-Kheng, Teixeira, Manuel R, Teo, Soo-Hwang, Terry, Kathryn L, Thompson, Pamela J, Thomsen, Liv Cecilie Vestrheim, Thull, Darcy L, Tihomirova, Laima, Tinker, Anna V, Tischkowitz, Marc, Tognazzo, Silvia, Toland, Amanda Ewart, Tone, Alicia, Trabert, Britton, Travis, Ruth C, Trichopoulou, Antonia, Tung, Nadine, Tworoger, Shelley S, van Altena, Anne M, Van Den Berg, David, van der Hout, Annemarie H, van der Luijt, Rob B, Van Heetvelde, Mattias, Van Nieuwenhuysen, Els, van Rensburg, Elizabeth J, Vanderstichele, Adriaan, Varon-Mateeva, Raymonda, Vega, Ana, Edwards, Digna Velez, Vergote, Ignace, Vierkant, Robert A, Vijai, Joseph, Vratimos, Athanassios, Walker, Lisa, Walsh, Christine, Wand, Dorothea, Wang-Gohrke, Shan, Wappenschmidt, Barbara, Webb, Penelope M, Weinberg, Clarice R, Weitzel, Jeffrey N, Wentzensen, Nicolas, Whittemore, Alice S, Wijnen, Juul T, Wilkens, Lynne R, Wolk, Alicja, Woo, Michelle, Wu, Xifeng, Wu, Anna H, Yang, Hannah, Yannoukakos, Drakoulis, Ziogas, Argyrios, Zorn, Kristin K, Narod, Steven A, Easton, Douglas F, Amos, Christopher I, Schildkraut, Joellen M, Ramus, Susan J, Ottini, Laura, Goodman, Marc T, Park, Sue K, Kelemen, Linda E, Risch, Harvey A, Thomassen, Mads, Offit, Kenneth, Simard, Jacques, Schmutzler, Rita Katharina, Hazelett, Dennis, Monteiro, Alvaro N, Couch, Fergus J, Berchuck, Andrew, Chenevix-Trench, Georgia, Goode, Ellen L, Sellers, Thomas A, Gayther, Simon A, Antoniou, Antonis C, and Pharoah, Paul D P
Published: 2017
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11. Association of breast cancer risk in BRCA1 and BRCA2 mutation carriers with genetic variants showing differential allelic expression: identification of a modifier of breast cancer risk at locus 11q22.3

Author: Hamdi, Yosr, Soucy, Penny, Kuchenbaeker, Karoline B., Pastinen, Tomi, Droit, Arnaud, Lemaçon, Audrey, Adlard, Julian, Aittomäki, Kristiina, Andrulis, Irene L., Arason, Adalgeir, Arnold, Norbert, Arun, Banu K., Azzollini, Jacopo, Bane, Anita, Barjhoux, Laure, Barrowdale, Daniel, Benitez, Javier, Berthet, Pascaline, Blok, Marinus J., Bobolis, Kristie, Bonadona, Valérie, Bonanni, Bernardo, Bradbury, Angela R., Brewer, Carole, Buecher, Bruno, Buys, Saundra S., Caligo, Maria A., Chiquette, Jocelyne, Chung, Wendy K., Claes, Kathleen B. M., Daly, Mary B., Damiola, Francesca, Davidson, Rosemarie, De la Hoya, Miguel, De Leeneer, Kim, Diez, Orland, Ding, Yuan Chun, Dolcetti, Riccardo, Domchek, Susan M., Dorfling, Cecilia M., Eccles, Diana, Eeles, Ros, Einbeigi, Zakaria, Ejlertsen, Bent, Engel, Christoph, Gareth Evans, D., Feliubadalo, Lidia, Foretova, Lenka, Fostira, Florentia, Foulkes, William D., Fountzilas, George, Friedman, Eitan, Frost, Debra, Ganschow, Pamela, Ganz, Patricia A., Garber, Judy, Gayther, Simon A., Gerdes, Anne-Marie, Glendon, Gord, Godwin, Andrew K., Goldgar, David E., Greene, Mark H., Gronwald, Jacek, Hahnen, Eric, Hamann, Ute, Hansen, Thomas V. O., Hart, Steven, Hays, John L., Hogervorst, Frans B. L., Hulick, Peter J., Imyanitov, Evgeny N., Isaacs, Claudine, Izatt, Louise, Jakubowska, Anna, James, Paul, Janavicius, Ramunas, Jensen, Uffe Birk, John, Esther M., Joseph, Vijai, Just, Walter, Kaczmarek, Katarzyna, Karlan, Beth Y., Kets, Carolien M., Kirk, Judy, Kriege, Mieke, Laitman, Yael, Laurent, Maïté, Lazaro, Conxi, Leslie, Goska, Lester, Jenny, Lesueur, Fabienne, Liljegren, Annelie, Loman, Niklas, Loud, Jennifer T., Manoukian, Siranoush, Mariani, Milena, Mazoyer, Sylvie, McGuffog, Lesley, Meijers-Heijboer, Hanne E. J., Meindl, Alfons, Miller, Austin, Montagna, Marco, Mulligan, Anna Marie, Nathanson, Katherine L., Neuhausen, Susan L., Nevanlinna, Heli, Nussbaum, Robert L., Olah, Edith, Olopade, Olufunmilayo I., Ong, Kai-ren, Oosterwijk, Jan C., Osorio, Ana, Papi, Laura, Park, Sue Kyung, Pedersen, Inge Sokilde, Peissel, Bernard, Segura, Pedro Perez, Peterlongo, Paolo, Phelan, Catherine M., Radice, Paolo, Rantala, Johanna, Rappaport-Fuerhauser, Christine, Rennert, Gad, Richardson, Andrea, Robson, Mark, Rodriguez, Gustavo C., Rookus, Matti A., Schmutzler, Rita Katharina, Sevenet, Nicolas, Shah, Payal D., Singer, Christian F., Slavin, Thomas P., Snape, Katie, Sokolowska, Johanna, Sønderstrup, Ida Marie Heeholm, Southey, Melissa, Spurdle, Amanda B., Stadler, Zsofia, Stoppa-Lyonnet, Dominique, Sukiennicki, Grzegorz, Sutter, Christian, Tan, Yen, Tea, Muy-Kheng, Teixeira, Manuel R., Teulé, Alex, Teo, Soo-Hwang, Terry, Mary Beth, Thomassen, Mads, Tihomirova, Laima, Tischkowitz, Marc, Tognazzo, Silvia, Toland, Amanda Ewart, Tung, Nadine, van den Ouweland, Ans M. W., van der Luijt, Rob B., van Engelen, Klaartje, van Rensburg, Elizabeth J., Varon-Mateeva, Raymonda, Wappenschmidt, Barbara, Wijnen, Juul T., Rebbeck, Timothy, Chenevix-Trench, Georgia, Offit, Kenneth, Couch, Fergus J., Nord, Silje, Easton, Douglas F., Antoniou, Antonis C., Simard, Jacques, EMBRACE, GEMO Study Collaborators, HEBON, and KConFab Investigators
Published: 2017
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12. Implementierung und Evaluation eines Decision Coaching Programms für gesunde BRCA1/2 Mutationsträgerinnen - Ergebnisse der randomisierten kontrollierten EDCP-BRCA

Author: Isselhard, Anna, Töpper, Maren, Lautz, Zoe, Vitinius, Frank, Fischer, Hannah, Berger-Höger, Birte, Steckelberg, Anke, Beifus, Karolina, Köberlein-Neu, Juliane, Rhiem, Kerstin, Schmutzler, Rita Katharina, and Stock, Stephanie
Subjects: ddc: 610, Medicine and health
Abstract: Hintergrund und Stand (inter)nationaler Forschung: Bei rund 5–10% aller neuen Brust- und Eierstockkrebsdiagnosen liegt eine pathogene BRCA1 oder BRCA2 Mutation zugrunde. Gesunde Frauen, bei denen eine dieser Mutationen festgestellt wird, haben im Rahmen der risikoadaptierten Prävention [zum vollständigen Text gelangen Sie über die oben angegebene URL]
Published: 2022

13. Präventives Versorgungskonzept bei erblichem Brustkrebs

Author: Rhiem, Kerstin, Schmutzler, Rita Katharina, Kirch, Wilhelm, editor, Badura, Bernhard, editor, and Pfaff, Holger, editor
Published: 2008
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14. Familiäres Mammakarzinom: Beratung, Gendiagnostik und Betreuung betroffener Familien

Author: Schmutzler, Rita Katharina, Meindl, Alfons, Kreienberg, Rolf, Jonat, Walter, Volm, Tanja, Möbus, Volker, and Alt, Dieter
Published: 2006
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15. Satisfaction and Quality of Life of Healthy and Unilateral Diseased BRCA1/2 Pathogenic Variant Carriers after Risk-Reducing Mastectomy and Reconstruction Using the BREAST-Q Questionnaire

Author: Herold, Natalie, primary, Hellmich, Martin, additional, Lichtenheldt, Frank, additional, Ataseven, Beyhan, additional, Hillebrand, Vanessa, additional, Wappenschmidt, Barbara, additional, Schmutzler, Rita Katharina, additional, and Rhiem, Kerstin, additional
Published: 2022
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16. Satisfaction and Quality of Life of Healthy and Unilateral Diseased BRCA1/2 Pathogenic Variant Carriers after Risk-Reducing Mastectomy and Reconstruction Using the BREAST-Q Questionnaire

Author: Herold, Natalie, Hellmich, Martin, Lichtenheldt, Frank, Ataseven, Beyhan, Hillebrand, Vanessa, Wappenschmidt, Barbara, Schmutzler, Rita Katharina, Rhiem, Kerstin, Herold, Natalie, Hellmich, Martin, Lichtenheldt, Frank, Ataseven, Beyhan, Hillebrand, Vanessa, Wappenschmidt, Barbara, Schmutzler, Rita Katharina, and Rhiem, Kerstin
Abstract: Risk-reducing mastectomy (RRM) is the most efficient form of breast cancer (BC) risk reduction in BRCA1/2 pathogenic variant (pV) carriers. However, this intervention in physical integrity is associated with significant morbidity. We assessed long-term perception of satisfaction and health-related quality of life (QoL) after bilateral RRM and reconstruction using the validated BREAST-Q. We searched the prospective database of the Center for Hereditary Breast and Ovarian Cancer Cologne for previvors and survivors who underwent bilateral RRM from 1994 to 2015 and evaluated the results of their BREAST-Q scores. The study enrolled 43 previvors and 90 survivors after a mean follow-up of 46.3 +/- 45.3 months after RRM. Satisfaction and QoL were independent of the technique of RRM or type of reconstruction but depended on the time of RRM. Compared to survivors, previvors had significantly higher mean satisfaction scores in their psychosocial, sexual, and physical well-being (chest) in both modules. Among previvors and survivors, higher psychological well-being correlated with a higher satisfaction with information and higher satisfaction with outcome. As psychological well-being correlated with satisfaction with information and outcome, we developed decision aids to improve shared decision making and long-term satisfaction with the decision and the postoperative outcome.
Published: 2022

17. Erste zielgerichtete Therapie bei Ovarialkarzinom für BRCA1/2-Mutationsträgerinnen zugelassen

Author: Schmutzler, Rita Katharina and Meindl, Alfons
Published: 2015
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18. 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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19. First international workshop of the ATM and cancer risk group (4-5 December 2019)

Author: Lesueur, Fabienne, Easton, Douglas F, Renault, Anne-Laure, Tavtigian, Sean V, Bernstein, Jonine L, Kote-Jarai, Zsofia, Eeles, Rosalind A, Plaseska-Karanfia, Dijana, Feliubadaló, Lidia, Spanish ATM Working Group, Arun, Banu, Herold, Natalie, Versmold, Beatrix, Schmutzler, Rita Katharina, GC-HBOC, Nguyen-Dumont, Tú, Southey, Melissa C, Dorling, Leila, Dunning, Alison M, Ghiorzo, Paola, Dalmasso, Bruna Samia, Cavaciuti, Eve, Le Gal, Dorothée, Roberts, Nicholas J, Dominguez-Valentin, Mev, Rookus, Matti, Taylor, Alexander MR, Goldstein, Alisa M, Goldgar, David E, CARRIERS And Ambry Groups, Stoppa-Lyonnet, Dominique, Andrieu, Nadine, Andrieu, Nadine [0000-0001-8820-5550], and Apollo - University of Cambridge Repository
Subjects: Heterozygote, Variants classification, Tumor profiles, Breast Neoplasms, Ataxia Telangiectasia Mutated Proteins, Cancer spectrum, Cancer risk, Ataxia Telangiectasia, ATM, Neoplasms, Humans, Female, Genetic Predisposition to Disease, France
Abstract: The first International Workshop of the ATM and Cancer Risk group focusing on the role of Ataxia-Telangiectasia Mutated (ATM) gene in cancer was held on December 4 and 5, 2019 at Institut Curie in Paris, France. It was motivated by the fact that germline ATM pathogenic variants have been found to be associated with different cancer types. However, due to the lack of precise age-, sex-, and site-specific risk estimates, no consensus on management guidelines for variant carriers exists, and the clinical utility of ATM variant testing is uncertain. The meeting brought together epidemiologists, geneticists, biologists and clinicians to review current knowledge and on-going challenges related to ATM and cancer risk. This report summarizes the meeting sessions content that covered the latest results in family-based and population-based studies, the importance of accurate variant classification, the effect of radiation exposures for ATM variant carriers, and the characteristics of ATM-deficient tumors. The report concludes that ATM variant carriers outside of the context of Ataxia-Telangiectasia may benefit from effective cancer risk management and therapeutic strategies and that efforts to set up large-scale studies in the international framework to achieve this goal are necessary.
Published: 2021
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20. Gewissensentscheidungen im Umgang mit Erkrankungsrisiken: medizinische, ethische und sozialrechtliche Aspekte

Author: Schmutzler, Rita Katharina, primary
Published: 2014
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21. Quality and Quantity: How to Organize a Countrywide Genetic Counseling and Testing

Author: Schmutzler, Rita Katharina and Schmutzler, Rita Katharina
Abstract: Background: About 30% of all women with breast or ovarian cancer exhibit a family history of the disease. So far, the genetic cause could be deciphered in about 30% of these cases. The results demonstrate a high genetic heterogeneity, with high-risk and moderate-risk genes and low-risk variants contributing alone or in concert to the development of cancer. Furthermore, it has been shown that the genotype significantly determines the phenotype and that knowledge of the phenotype is as important as the genotype to offer adequate and risk-adapted prevention to persons at risk. For newly identified risk genes, however, the phenotype is not sufficiently characterized at first, and thus prevention measures are not sufficiently evaluated. Summary: The German Consortium for Hereditary Breast and Ovarian Cancer has developed a concept for collecting the missing data in the context of knowledge-generating care and at the same time ensuring care based on the best available knowledge. Core elements of this concept are: structured and standardized care, an outcome-oriented evaluation based on a comprehensive registry, networking with certified breast and gynecological cancer centers combined with regular training on state-of-the-art care for doctors, and compilation of comprehensible patient information. This comprehensive concept has been incorporated into contracts for specialized care with health insurers and thus ensures nationwide care at the highest scientific and clinical levels. Key Messages: This article describes how to implement a concept of evidence-generating care for risk-adjusted prevention in a nationwide health care system.
Published: 2021

22. Breast Cancer Risk in Familial CHEK2 Germline Mutation Carriers is Modified by the Polygenic Risk Score: A Multicenter Study by the German Consortium for Hereditary Breast and Ovarian Cancer

Author: Borde, Julika, Ernst, Corinna, Weber-Lassalle, Konstantin, Niederacher, Dieter, Hauke, Jan, Horvath, Judit, Weber-Lassalle, Nana, Meindl, Alfons, Bernd, Auber, Pohl-Rescigno, Esther, Arnold, Norbert, Lee, Andrew, Engel, Christoph, Wappenschmidt, Barbara, Schmidt, Marjanka, Antoniou, Antonis, Schmutzler, Rita Katharina, Kuchenbaecker, Karoline, Hahnen, Eric, Borde, Julika, Ernst, Corinna, Weber-Lassalle, Konstantin, Niederacher, Dieter, Hauke, Jan, Horvath, Judit, Weber-Lassalle, Nana, Meindl, Alfons, Bernd, Auber, Pohl-Rescigno, Esther, Arnold, Norbert, Lee, Andrew, Engel, Christoph, Wappenschmidt, Barbara, Schmidt, Marjanka, Antoniou, Antonis, Schmutzler, Rita Katharina, Kuchenbaecker, Karoline, and Hahnen, Eric
Published: 2020

23. Quality and Quantity: How to Organize a Countrywide Genetic Counseling and Testing

Author: Schmutzler, Rita Katharina, primary
Published: 2021
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24. Risikoadaptierte Prävention bei familiär bedingtem Brust- und Eierstockkrebs

Author: Schmutzler, Rita Katharina, primary
Published: 2020
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25. Correction: Evaluation of copy-number variants as modifiers of breast and ovarian cancer risk for BRCA1 pathogenic variant carriers

Author: Walker, Logan C, Marquart, Louise, Pearson, John F, Wiggins, George AR, O'Mara, Tracy A, Parsons, Michael T, BCFR, Barrowdale, Daniel, McGuffog, Lesley, Dennis, Joe, Benitez, Javier, Slavin, Thomas P, Radice, Paolo, Frost, Debra, EMBRACE, Godwin, Andrew K, Meindl, Alfons, Schmutzler, Rita Katharina, GEMO Study Collaborators, Isaacs, Claudine, Peshkin, Beth N, Caldes, Trinidad, Hogervorst, Frans BL, HEBON, Lazaro, Conxi, Jakubowska, Anna, Montagna, Marco, KConFab Investigators, Chen, Xiaoqing, Offit, Kenneth, Hulick, Peter J, Andrulis, Irene L, Lindblom, Annika, Nussbaum, Robert L, Nathanson, Katherine L, Chenevix-Trench, Georgia, Antoniou, Antonis C, Couch, Fergus J, Spurdle, Amanda B, Dennis, Joseph [0000-0003-4591-1214], Antoniou, Antonis [0000-0001-9223-3116], and Apollo - University of Cambridge Repository
Subjects: GEMO Study Collaborators, BCFR, KConFab Investigators, HEBON, EMBRACE
Abstract: This Article was originally published under a CC BY-NC-SA 4.0 license, but has now been made available under a CC BY 4.0 license. The PDF and HTML versions of the Article have been modified accordingly.
Published: 2019

26. Benchmarking of a checklist for the identification of familial risk for breast and ovarian cancers in a prospective cohort

Author: Rhiem, Kerstin, Buecker-Nott, Hans-Joachim, Hellmich, Martin, Fischer, Holger, Ataseven, Beyhan, Dittmer-Grabowski, Christine, Latos, Kunibert, Pelzer, Volker, Seifert, Manuela, Schmidt, Andrea, Rezek, Daniela, Groh, Ulrich, Meinerz, Wolfgang, Crommelinck, Dirk, Hahnen, Eric, Wesselmann, Simone, Schmutzler, Rita Katharina, Rhiem, Kerstin, Buecker-Nott, Hans-Joachim, Hellmich, Martin, Fischer, Holger, Ataseven, Beyhan, Dittmer-Grabowski, Christine, Latos, Kunibert, Pelzer, Volker, Seifert, Manuela, Schmidt, Andrea, Rezek, Daniela, Groh, Ulrich, Meinerz, Wolfgang, Crommelinck, Dirk, Hahnen, Eric, Wesselmann, Simone, and Schmutzler, Rita Katharina
Abstract: The detection of deleterious germline mutations in BRCA1 and BRCA2 considerably influences the clinical management of healthy and diseased carriers. Therefore, the identification of persons at risk who could uptake genetic counseling and testing is pivotal. We developed a checklist with validated criteria to improve the identification, and prospectively evaluate the incidence, of familial cancer history in 5091 breast cancer patients. The rate of 30.4% of patients at high genetic risk underpins the demand for care in risk identification and counseling. The easy-to-use instrument promotes the implementation and dissemination of risk counseling by physicians.
Published: 2019

27. Gezielte Früherkennung und risikoadaptierte Therapie

Author: Bokemeyer, Carsten, Engert, Andreas, Gökbuget, Nicola, Schmutzler, Rita Katharina, Bokemeyer, Carsten, Engert, Andreas, Gökbuget, Nicola, and Schmutzler, Rita Katharina
Abstract: Gezielte Früherkennung am Beispiel des Deutschen Konsortiums Familiärer Brust- und Eierstockkrebs / Rita Schmutzler Modelle für eine erfolgreiche, risikoadaptierte Therapie – am Beispiel der akuten lymphatischen Leukämie / Nicola Gökbuget Modelle für eine erfolgreiche, risikoadaptierte Therapie – am Beispiel des Hodgkin-Lymphoms / Andreas Engert Modelle für eine erfolgreiche, risikoadaptierte Therapie – am Beispiel der Keimzelltumoren des Mannes / Carsten Bokemeyer
Published: 2019

28. Interdisziplinäre Früherkennung, Diagnostik, Therapie und Nachsorge des Mammakarzinoms : Leitlinie der DGGG und DKG (S3-Level, AWMF-Registernummer 032/045OL, Dezember 2017) – Teil 1 mit Empfehlungen zur Früherkennung, Diagnostik und Nachsorge des Mammakarzinoms

Author: Wöckel, Achim, Festl, Jasmin, Stüber, Tanja, Brust, Katharina, Stangl, Stephanie, Heuschmann, Peter Ulrich, Albert, Ute Susann, Budach, Wilfried, Follmann, Markus, Janni, Wolfgang, Kopp, Ina, Kreienberg, Rolf, Kühn, Thorsten, Langer, Thomas, Nothacker, Monika, Scharl, Anton, Schreer, Ingrid, Link, Hartmut, Engel, Jutta, Fehm, Tanja, Weis, Joachim, Welt, Anja, Steckelberg, Anke, Feyer, Petra, König, Klaus, Hahne, Andrea, Kreipe, Hans H., Knoefel, Wolfram Trudo, Denkinger, Michael, Brucker, Sara, Lüftner, Diana, Kubisch, Christian, Gerlach, Christina, Lebeau, Annette, Siedentopf, Friederike, Petersen, Cordula, Bartsch, Hans Helge, Schulz-Wendtland, Rüdiger, Hahn, Markus, Hanf, Volker, Müller-Schimpfle, Markus, Henscher, Ulla, Roncarati, Renza, Katalinic, Alexander, Heitmann, Christoph, Honegger, Christoph, Paradies, Kerstin, Bjelic-Radisic, Vesna, Degenhardt, Friedrich, Wenz, Frederik, Rick, Oliver, Hölzel, Dieter, Zaiss, Matthias, Kemper, Gudrun, Budach, Volker, Denkert, Carsten Michael, Gerber , Bernd, Tesch, Hans, Hirsmüller, Susanne, Sinn, Hans-Peter, Dunst, Jürgen, Münstedt, Karsten, Bick, Ulrich, Fallenberg, Eva, Tholen, Reina, Hung, Roswita, Baumann, Freerk T., Beckmann, Matthias Wilhelm, Blohmer, Jens-Uwe, Fasching, Peter Andreas, Lux, Michael Patrick, Harbeck, Nadia, Hadji, Peyman, Hauner, Hans, Heywang-Köbrunner, Sylvia H., Huober, Jens, Hübner, Jutta, Jackisch, Christian, Loibl, Sibylle, Lück, Hans-Jürgen, Minckwitz, Gunter von, Möbus, Volker, Müller, Volkmar, Nöthlings, Ute, Schmidt, Marcus, Schmutzler, Rita Katharina, Schneeweiss, Andreas, Schütz, Florian, Stickeler, Elmar, Thomssen, Christoph, Untch, Michael, Wesselmann, Simone, Bücker, Arno, and Krockenberger, Mathias
Subjects: ddc:610
Abstract: Purpose: The aim of this official guideline coordinated and published by the German Society for Gynecology and Obstetrics (DGGG) and the German Cancer Society (DKG) was to optimize the screening, diagnosis, therapy and follow-up care of breast cancer. Methods: The process of updating the S3 guideline dating from 2012 was based on the adaptation of identified source guidelines which were combined with reviews of evidence compiled using PICO (Patients/Interventions/Control/Outcome) questions and the results of a systematic search of literature databases and the selection and evaluation of the identified literature. The interdisciplinary working groups took the identified materials as their starting point to develop recommendations and statements which were modified and graded in a structured consensus procedure. Recommendations: Part 1 of this short version of the guideline presents recommendations for the screening, diagnosis and follow-up care of breast cancer. The importance of mammography for screening is confirmed in this updated version of the guideline and forms the basis for all screening. In addition to the conventional methods used to diagnose breast cancer, computed tomography (CT) is recommended for staging in women with a higher risk of recurrence. The follow-up concept includes suggested intervals between physical, ultrasound and mammography examinations, additional high-tech diagnostic procedures, and the determination of tumor markers for the evaluation of metastatic disease. Ziele: Das Ziel dieser offiziellen Leitlinie, die von der Deutschen Gesellschaft für Gynäkologie und Geburtshilfe (DGGG) und der Deutschen Krebsgesellschaft (DKG) publiziert und koordiniert wurde, ist es, die Früherkennung, Diagnostik, Therapie und Nachsorge des Mammakarzinoms zu optimieren. Methoden: Der Aktualisierungsprozess der S3-Leitlinie aus 2012 basierte zum einen auf der Adaptation identifizierter Quellleitlinien und zum anderen auf Evidenzübersichten, die nach Entwicklung von PICO-(Patients/Interventions/Control/Outcome-)Fragen, systematischer Recherche in Literaturdatenbanken sowie Selektion und Bewertung der gefundenen Literatur angefertigt wurden. In den interdisziplinären Arbeitsgruppen wurden auf dieser Grundlage Vorschläge für Empfehlungen und Statements erarbeitet, die im Rahmen von strukturierten Konsensusverfahren modifiziert und graduiert wurden. Empfehlungen: Der Teil 1 dieser Kurzversion der Leitlinie zeigt Empfehlungen zur Früherkennung, Diagnostik und Nachsorge des Mammakarzinoms: Der Stellenwert des Mammografie-Screenings wird in der aktualisierten Leitlinienversion bestätigt und bildet damit die Grundlage der Früherkennung. Neben den konventionellen Methoden der Karzinomdiagnostik wird die Computertomografie (CT) zum Staging bei höherem Rückfallrisiko empfohlen. Die Nachsorgekonzepte beinhalten Untersuchungsintervalle für die körperliche Untersuchung, Ultraschall und Mammografie, während weiterführende Gerätediagnostik und Tumormarkerbestimmungen bei der metastasierten Erkrankung Anwendung finden.
Published: 2018

29. Benchmarking of a checklist for the identification of familial risk for breast and ovarian cancers in a prospective cohort

Author: Rhiem, Kerstin, primary, Bücker‐Nott, Hans‐Joachim, additional, Hellmich, Martin, additional, Fischer, Holger, additional, Ataseven, Beyhan, additional, Dittmer‐Grabowski, Christine, additional, Latos, Kunibert, additional, Pelzer, Volker, additional, Seifert, Manuela, additional, Schmidt, Andrea, additional, Rezek, Daniela, additional, Groh, Ulrich, additional, Meinerz, Wolfgang, additional, Crommelinck, Dirk, additional, Hahnen, Eric, additional, Wesselmann, Simone, additional, and Schmutzler, Rita Katharina, additional
Published: 2019
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30. Mutational spectrum in a worldwide study of 29,700 families with BRCA1 or BRCA2 mutations

Author: Rebbeck, Timothy R., Friebel, Tara M., Friedman, Eitan, Hamann, Ute, Huo, Dezheng, Kwong, Ava, Olah, Edith, Olopade, Olufunmilayo I., Solano, Angela R., Teo, Soo-Hwang, Thomassen, Mads, Weitzel, Jeffrey N., Chan, T. L., Couch, Fergus J., Goldgar, David E., Kruse, Torben A., Palmero, Edenir Inez, Park, Sue Kyung, Torres, Diana, van Rensburg, Elizabeth J., McGuffog, Lesley, Parsons, Michael T., Leslie, Goska, Aalfs, Cora M., Abugattas, Julio, Adlard, Julian, Agata, Simona, Aittomaki, Kristiina, Andrews, Lesley, Andrulis, Irene L., Arason, Adalgeir, Arnold, Norbert, Arun, Banu K., Asseryanis, Ella, Auerbach, Leo, Azzollini, Jacopo, Balmana, Judith, Barile, Monica, Barkardottir, Rosa B., Barrowdale, Daniel, Benitez, Javier, Berger, Andreas, Berger, Raanan, Blanco, Amie M., Blazer, Kathleen R., Blok, Marinus J., Bonadona, Valerie, Bonanni, Bernardo, Bradbury, Angela R., Brewer, Carole, Buecher, Bruno, Buys, Saundra S., Caldes, Trinidad, Caliebe, Almuth, Caligo, Maria A., Campbell, Ian, Caputo, Sandrine M., Chiquette, Jocelyne, Chung, Wendy K., Claes, Kathleen B. M., Collee, J. Margriet, Cook, Jackie, Davidson, Rosemarie, de la Hoya, Miguel, De Leeneer, Kim, de Pauw, Antoine, Delnatte, Capucine, Diez, Orland, Ding, Yuan Chun, Ditsch, Nina, Domchek, SusanM., Dorfling, Cecilia M., Velazquez, Carolina, Dworniczak, Bernd, Eason, Jacqueline, Easton, Douglas F., Eeles, Ros, Ehrencrona, Hans, Ejlertsen, Bent, Engel, Christoph, Engert, Stefanie, Evans, D. Gareth, Faivre, Laurence, Feliubadalo, Lidia, Ferrer, Sandra Fert, Foretova, Lenka, Fowler, Jeffrey, Frost, Debra, Galvao, Henrique C. R., Ganz, Patricia A., Garber, Judy, Gauthier-Villars, Marion, Gehrig, Andrea, Gerdes, Anne-Marie, Gesta, Paul, Giannini, Giuseppe, Giraud, Sophie, Glendon, Gord, Godwin, Andrew K., Greene, Mark H., Gronwald, Jacek, Gutierrez-Barrera, Angelica, Hahnen, Eric, Hauke, Jan, Henderson, Alex, Hentschel, Julia, Hogervorst, Frans B. L., Honisch, Ellen, Imyanitov, Evgeny N., Isaacs, Claudine, Izatt, Louise, Izquierdo, Angel, Jakubowska, Anna, James, Paul, Janavicius, Ramunas, Jensen, Uffe Birk, John, Esther M., Vijai, Joseph, Kaczmarek, Katarzyna, Karlan, Beth Y., Kast, Karin, Kim, Sung-Won, Konstantopoulou, Irene, Korach, Jacob, Laitman, Yael, Lasa, Adriana, Lasset, Christine, Lazaro, Conxi, Lee, Annette, Lee, Min Hyuk, Lester, Jenny, Lesueur, Fabienne, Liljegren, Annelie, Lindor, Noralane M., Longy, Michel, Loud, Jennifer T., Lu, Karen H., Lubinski, Jan, Machackova, Eva, Manoukian, Siranoush, Mari, Veronique, Martinez-Bouzas, Cristina, Matrai, Zoltan, Mebirouk, Noura, Meijers-Heijboer, Hanne E. J., Meindl, Alfons, Mensenkamp, Arjen R., Mickys, Ugnius, Miller, Austin, Montagna, Marco, Moysich, Kirsten B., Mulligan, Anna Marie, Musinsky, Jacob, Neuhausen, Susan L., Nevanlinna, Heli, Ngeow, Joanne, Nguyen, Huu Phuc, Niederacher, Dieter, Nielsen, Henriette Roed, Nielsen, Finn Cilius, Nussbaum, Robert L., Offit, Kenneth, Ofverholm, Anna, Ong, Kai-ren, Osorio, Ana, Papi, Laura, Papp, Janos, Pasini, Barbara, Pedersen, Inge Sokilde, Peixoto, Ana, Peruga, Nina, Peterlongo, Paolo, Pohl, Esther, Pradhan, Nisha, Prajzendanc, Karolina, Prieur, Fabienne, Pujol, Pascal, Radice, Paolo, Ramus, Susan J., Rantala, Johanna, Rashid, Muhammad Usman, Rhiem, Kerstin, Robson, Mark, Rodriguez, Gustavo C., Rogers, Mark T., Rudaitis, Vilius, Schmidt, Ane Y., Schmutzler, Rita Katharina, Senter, Leigha, Shah, Payal D., Sharma, Priyanka, Side, Lucy E., Simard, Jacques, Singer, Christian F., Skytte, Anne-Bine, Slavin, Thomas P., Snape, Katie, Sobol, Hagay, Southey, Melissa, Steele, Linda, Steinemann, Doris, Sukiennicki, Grzegorz, Sutter, Christian, Szabo, Csilla I., Tan, Yen Y., Teixeira, Manuel R., Terry, Mary Beth, Teule, Alex, Thomas, Abigail, Thull, Darcy L., Tischkowitz, Marc, Tognazzo, Silvia, Toland, Amanda Ewart, Topka, Sabine, Trainer, Alison H., Tung, Nadine, van Asperen, Christi J., van der Hout, Annemieke H., van der Kolk, Lizet E., van der Luijt, Rob B., Van Heetvelde, Mattias, Varesco, Liliana, Varon-Mateeva, Raymonda, Vega, Ana, Villarreal-Garza, Cynthia, von Wachenfeldt, Anna, Walker, Lisa, Wang-Gohrke, Shan, Wappenschmidt, Barbara, Weber, Bernhard H. F., Yannoukakos, Drakoulis, Yoon, Sook-Yee, Zanzottera, Cristina, Zidan, Jamal, Zorn, Kristin K., Selkirk, Christina G. Hutten, Hulick, Peter J., Chenevix-Trench, Georgia, Spurdle, Amanda B., Antoniou, Antonis C., Nathanson, Katherine L., Rebbeck, Timothy R., Friebel, Tara M., Friedman, Eitan, Hamann, Ute, Huo, Dezheng, Kwong, Ava, Olah, Edith, Olopade, Olufunmilayo I., Solano, Angela R., Teo, Soo-Hwang, Thomassen, Mads, Weitzel, Jeffrey N., Chan, T. L., Couch, Fergus J., Goldgar, David E., Kruse, Torben A., Palmero, Edenir Inez, Park, Sue Kyung, Torres, Diana, van Rensburg, Elizabeth J., McGuffog, Lesley, Parsons, Michael T., Leslie, Goska, Aalfs, Cora M., Abugattas, Julio, Adlard, Julian, Agata, Simona, Aittomaki, Kristiina, Andrews, Lesley, Andrulis, Irene L., Arason, Adalgeir, Arnold, Norbert, Arun, Banu K., Asseryanis, Ella, Auerbach, Leo, Azzollini, Jacopo, Balmana, Judith, Barile, Monica, Barkardottir, Rosa B., Barrowdale, Daniel, Benitez, Javier, Berger, Andreas, Berger, Raanan, Blanco, Amie M., Blazer, Kathleen R., Blok, Marinus J., Bonadona, Valerie, Bonanni, Bernardo, Bradbury, Angela R., Brewer, Carole, Buecher, Bruno, Buys, Saundra S., Caldes, Trinidad, Caliebe, Almuth, Caligo, Maria A., Campbell, Ian, Caputo, Sandrine M., Chiquette, Jocelyne, Chung, Wendy K., Claes, Kathleen B. M., Collee, J. Margriet, Cook, Jackie, Davidson, Rosemarie, de la Hoya, Miguel, De Leeneer, Kim, de Pauw, Antoine, Delnatte, Capucine, Diez, Orland, Ding, Yuan Chun, Ditsch, Nina, Domchek, SusanM., Dorfling, Cecilia M., Velazquez, Carolina, Dworniczak, Bernd, Eason, Jacqueline, Easton, Douglas F., Eeles, Ros, Ehrencrona, Hans, Ejlertsen, Bent, Engel, Christoph, Engert, Stefanie, Evans, D. Gareth, Faivre, Laurence, Feliubadalo, Lidia, Ferrer, Sandra Fert, Foretova, Lenka, Fowler, Jeffrey, Frost, Debra, Galvao, Henrique C. R., Ganz, Patricia A., Garber, Judy, Gauthier-Villars, Marion, Gehrig, Andrea, Gerdes, Anne-Marie, Gesta, Paul, Giannini, Giuseppe, Giraud, Sophie, Glendon, Gord, Godwin, Andrew K., Greene, Mark H., Gronwald, Jacek, Gutierrez-Barrera, Angelica, Hahnen, Eric, Hauke, Jan, Henderson, Alex, Hentschel, Julia, Hogervorst, Frans B. L., Honisch, Ellen, Imyanitov, Evgeny N., Isaacs, Claudine, Izatt, Louise, Izquierdo, Angel, Jakubowska, Anna, James, Paul, Janavicius, Ramunas, Jensen, Uffe Birk, John, Esther M., Vijai, Joseph, Kaczmarek, Katarzyna, Karlan, Beth Y., Kast, Karin, Kim, Sung-Won, Konstantopoulou, Irene, Korach, Jacob, Laitman, Yael, Lasa, Adriana, Lasset, Christine, Lazaro, Conxi, Lee, Annette, Lee, Min Hyuk, Lester, Jenny, Lesueur, Fabienne, Liljegren, Annelie, Lindor, Noralane M., Longy, Michel, Loud, Jennifer T., Lu, Karen H., Lubinski, Jan, Machackova, Eva, Manoukian, Siranoush, Mari, Veronique, Martinez-Bouzas, Cristina, Matrai, Zoltan, Mebirouk, Noura, Meijers-Heijboer, Hanne E. J., Meindl, Alfons, Mensenkamp, Arjen R., Mickys, Ugnius, Miller, Austin, Montagna, Marco, Moysich, Kirsten B., Mulligan, Anna Marie, Musinsky, Jacob, Neuhausen, Susan L., Nevanlinna, Heli, Ngeow, Joanne, Nguyen, Huu Phuc, Niederacher, Dieter, Nielsen, Henriette Roed, Nielsen, Finn Cilius, Nussbaum, Robert L., Offit, Kenneth, Ofverholm, Anna, Ong, Kai-ren, Osorio, Ana, Papi, Laura, Papp, Janos, Pasini, Barbara, Pedersen, Inge Sokilde, Peixoto, Ana, Peruga, Nina, Peterlongo, Paolo, Pohl, Esther, Pradhan, Nisha, Prajzendanc, Karolina, Prieur, Fabienne, Pujol, Pascal, Radice, Paolo, Ramus, Susan J., Rantala, Johanna, Rashid, Muhammad Usman, Rhiem, Kerstin, Robson, Mark, Rodriguez, Gustavo C., Rogers, Mark T., Rudaitis, Vilius, Schmidt, Ane Y., Schmutzler, Rita Katharina, Senter, Leigha, Shah, Payal D., Sharma, Priyanka, Side, Lucy E., Simard, Jacques, Singer, Christian F., Skytte, Anne-Bine, Slavin, Thomas P., Snape, Katie, Sobol, Hagay, Southey, Melissa, Steele, Linda, Steinemann, Doris, Sukiennicki, Grzegorz, Sutter, Christian, Szabo, Csilla I., Tan, Yen Y., Teixeira, Manuel R., Terry, Mary Beth, Teule, Alex, Thomas, Abigail, Thull, Darcy L., Tischkowitz, Marc, Tognazzo, Silvia, Toland, Amanda Ewart, Topka, Sabine, Trainer, Alison H., Tung, Nadine, van Asperen, Christi J., van der Hout, Annemieke H., van der Kolk, Lizet E., van der Luijt, Rob B., Van Heetvelde, Mattias, Varesco, Liliana, Varon-Mateeva, Raymonda, Vega, Ana, Villarreal-Garza, Cynthia, von Wachenfeldt, Anna, Walker, Lisa, Wang-Gohrke, Shan, Wappenschmidt, Barbara, Weber, Bernhard H. F., Yannoukakos, Drakoulis, Yoon, Sook-Yee, Zanzottera, Cristina, Zidan, Jamal, Zorn, Kristin K., Selkirk, Christina G. Hutten, Hulick, Peter J., Chenevix-Trench, Georgia, Spurdle, Amanda B., Antoniou, Antonis C., and Nathanson, Katherine L.
Abstract: The prevalence and spectrum of germline mutations in BRCA1 and BRCA2 have been reported in single populations, with the majority of reports focused on White in Europe and North America. The Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) has assembled data on 18,435 families with BRCA1 mutations and 11,351 families with BRCA2 mutations ascertained from 69 centers in 49 countries on six continents. This study comprehensively describes the characteristics of the 1,650 unique BRCA1 and 1,731 unique BRCA2 deleterious (disease-associated) mutations identified in the CIMBA database. We observed substantial variation in mutation type and frequency by geographical region and race/ethnicity. In addition to known founder mutations, mutations of relatively high frequency were identified in specific racial/ethnic or geographic groups that may reflect founder mutations and which could be used in targeted (panel) first pass genotyping for specific populations. Knowledge of the population-specific mutational spectrum in BRCA1 and BRCA2 could inform efficient strategies for genetic testing and may justify a more broad-based oncogenetic testing in some populations.
Published: 2018

31. Prevalence of pathogenic BRCA1/2 germline mutations among 802 women with unilateral triple-negative breast cancer without family cancer history

Author: German Consortium for Hereditary Breast and Ovarian Cancer (GC-HBOC), Engel, Christoph, Rhiem, Kerstin E. M., Hahnen, Eric Thomas, Loibl, Sibylle, Weber, Karsten E., Seiler, Sabine, Zachariae, Silke, Hauke, Jan, Wappenschmidt, Barbara, Waha, Anke, Blümcke, Britta, Kiechle, Marion, Meindl, Alfons, Niederacher, Dieter, Bartram, Claus R., Speiser, Dorothee, Schlegelberger, Brigitte, Arnold, Norbert, Wieacker, Peter, Leinert, Elena, Gehrig, Andrea, Briest, Susanne, Kast, Karin, Rieß, Olaf, Emons, Günter, Weber, Bernhard H. F., Engel, Jutta, Schmutzler, Rita Katharina, German Consortium for Hereditary Breast and Ovarian Cancer (GC-HBOC), Engel, Christoph, Rhiem, Kerstin E. M., Hahnen, Eric Thomas, Loibl, Sibylle, Weber, Karsten E., Seiler, Sabine, Zachariae, Silke, Hauke, Jan, Wappenschmidt, Barbara, Waha, Anke, Blümcke, Britta, Kiechle, Marion, Meindl, Alfons, Niederacher, Dieter, Bartram, Claus R., Speiser, Dorothee, Schlegelberger, Brigitte, Arnold, Norbert, Wieacker, Peter, Leinert, Elena, Gehrig, Andrea, Briest, Susanne, Kast, Karin, Rieß, Olaf, Emons, Günter, Weber, Bernhard H. F., Engel, Jutta, and Schmutzler, Rita Katharina
Abstract: Background: There is no international consensus up to which age women with a diagnosis of triple-negative breast cancer (TNBC) and no family history of breast or ovarian cancer should be offered genetic testing for germline BRCA1 and BRCA2 (gBRCA) mutations. Here, we explored the association of age at TNBC diagnosis with the prevalence of pathogenic gBRCA mutations in this patient group. Methods: The study comprised 802 women (median age 40 years, range 19–76) with oestrogen receptor, progesterone receptor, and human epidermal growth factor receptor type 2 negative breast cancers, who had no relatives with breast or ovarian cancer. All women were tested for pathogenic gBRCA mutations. Logistic regression analysis was used to explore the association between age at TNBC diagnosis and the presence of a pathogenic gBRCA mutation. Results: A total of 127 women with TNBC (15.8%) were gBRCA mutation carriers (BRCA1: n = 118, 14.7%; BRCA2: n = 9, 1.1%). The mutation prevalence was 32.9% in the age group 20–29 years compared to 6.9% in the age group 60–69 years. Logistic regression analysis revealed a significant increase of mutation frequency with decreasing age at diagnosis (odds ratio 1.87 per 10 year decrease, 95%CI 1.50–2.32, p < 0.001). gBRCA mutation risk was predicted to be > 10% for women diagnosed below approximately 50 years. Conclusions: Based on the general understanding that a heterozygous mutation probability of 10% or greater justifies gBRCA mutation screening, women with TNBC diagnosed before the age of 50 years and no familial history of breast and ovarian cancer should be tested for gBRCA mutations. In Germany, this would concern approximately 880 women with newly diagnosed TNBC per year, of whom approximately 150 are expected to be identified as carriers of a pathogenic gBRCA mutation.
Published: 2018

32. Interdisciplinary screening, diagnosis, therapy and follow-up of breast cancer : guideline of the DGGG and the DKG (S3-level, AWMF registry number 032/045OL, December 2017) – part 1 with recommendations for the screening, diagnosis and therapy of breast cancer

Author: Wöckel, Achim, Festl, Jasmin, Stüber, Tanja, Brust, Katharina, Stangl, Stephanie, Heuschmann, Peter Ulrich, Albert, Ute Susann, Budach, Wilfried, Follmann, Markus, Janni, Wolfgang, Kopp, Ina, Kreienberg, Rolf, Kühn, Thorsten, Langer, Thomas, Nothacker, Monika, Scharl, Anton, Schreer, Ingrid, Link, Hartmut, Engel, Jutta, Fehm, Tanja, Weis, Joachim, Welt, Anja, Steckelberg, Anke, Feyer, Petra, König, Klaus, Hahne, Andrea, Kreipe, Hans H., Knoefel, Wolfram Trudo, Denkinger, Michael, Brucker, Sara, Lüftner, Diana, Kubisch, Christian, Gerlach, Christina, Lebeau, Annette, Siedentopf, Friederike, Petersen, Cordula, Bartsch, Hans Helge, Schulz-Wendtland, Rüdiger, Hahn, Markus, Hanf, Volker, Müller-Schimpfle, Markus, Henscher, Ulla, Roncarati, Renza, Katalinic, Alexander, Heitmann, Christoph, Honegger, Christoph, Paradies, Kerstin, Bjelic-Radisic, Vesna, Degenhardt, Friedrich, Wenz, Frederik, Rick, Oliver, Hölzel, Dieter, Zaiss, Matthias, Kemper, Gudrun, Budach, Volker, Denkert, Carsten Michael, Gerber, Bernd, Tesch, Hans, Hirsmüller, Susanne, Sinn, Hans-Peter, Dunst, Jürgen, Münstedt, Karsten, Bick, Ulrich, Fallenberg, Eva, Tholen, Reina, Hung, Roswita, Baumann, Freerk T., Beckmann, Matthias Wilhelm, Blohmer, Jens-Uwe, Fasching, Peter Andreas, Lux, Michael Patrick, Harbeck, Nadia, Hadji, Peyman, Hauner, Hans, Heywang-Köbrunner, Sylvia H., Huober, Jens, Hübner, Jutta, Jackisch, Christian, Loibl, Sibylle, Lück, Hans-Jürgen, Minckwitz, Gunter von, Möbus, Volker, Müller, Volkmar, Nöthlings, Ute, Schmidt, Marcus, Schmutzler, Rita Katharina, Schneeweiss, Andreas, Schütz, Florian, Stickeler, Elmar, Thomssen, Christoph, Untch, Michael, Wesselmann, Simone, Bücker, Arno, Krockenberger, Mathias Heinric, Wöckel, Achim, Festl, Jasmin, Stüber, Tanja, Brust, Katharina, Stangl, Stephanie, Heuschmann, Peter Ulrich, Albert, Ute Susann, Budach, Wilfried, Follmann, Markus, Janni, Wolfgang, Kopp, Ina, Kreienberg, Rolf, Kühn, Thorsten, Langer, Thomas, Nothacker, Monika, Scharl, Anton, Schreer, Ingrid, Link, Hartmut, Engel, Jutta, Fehm, Tanja, Weis, Joachim, Welt, Anja, Steckelberg, Anke, Feyer, Petra, König, Klaus, Hahne, Andrea, Kreipe, Hans H., Knoefel, Wolfram Trudo, Denkinger, Michael, Brucker, Sara, Lüftner, Diana, Kubisch, Christian, Gerlach, Christina, Lebeau, Annette, Siedentopf, Friederike, Petersen, Cordula, Bartsch, Hans Helge, Schulz-Wendtland, Rüdiger, Hahn, Markus, Hanf, Volker, Müller-Schimpfle, Markus, Henscher, Ulla, Roncarati, Renza, Katalinic, Alexander, Heitmann, Christoph, Honegger, Christoph, Paradies, Kerstin, Bjelic-Radisic, Vesna, Degenhardt, Friedrich, Wenz, Frederik, Rick, Oliver, Hölzel, Dieter, Zaiss, Matthias, Kemper, Gudrun, Budach, Volker, Denkert, Carsten Michael, Gerber, Bernd, Tesch, Hans, Hirsmüller, Susanne, Sinn, Hans-Peter, Dunst, Jürgen, Münstedt, Karsten, Bick, Ulrich, Fallenberg, Eva, Tholen, Reina, Hung, Roswita, Baumann, Freerk T., Beckmann, Matthias Wilhelm, Blohmer, Jens-Uwe, Fasching, Peter Andreas, Lux, Michael Patrick, Harbeck, Nadia, Hadji, Peyman, Hauner, Hans, Heywang-Köbrunner, Sylvia H., Huober, Jens, Hübner, Jutta, Jackisch, Christian, Loibl, Sibylle, Lück, Hans-Jürgen, Minckwitz, Gunter von, Möbus, Volker, Müller, Volkmar, Nöthlings, Ute, Schmidt, Marcus, Schmutzler, Rita Katharina, Schneeweiss, Andreas, Schütz, Florian, Stickeler, Elmar, Thomssen, Christoph, Untch, Michael, Wesselmann, Simone, Bücker, Arno, and Krockenberger, Mathias Heinric
Abstract: Purpose: The aim of this official guideline coordinated and published by the German Society for Gynecology and Obstetrics (DGGG) and the German Cancer Society (DKG) was to optimize the screening, diagnosis, therapy and follow-up care of breast cancer. Methods: The process of updating the S3 guideline dating from 2012 was based on the adaptation of identified source guidelines which were combined with reviews of evidence compiled using PICO (Patients/Interventions/Control/Outcome) questions and the results of a systematic search of literature databases and the selection and evaluation of the identified literature. The interdisciplinary working groups took the identified materials as their starting point to develop recommendations and statements which were modified and graded in a structured consensus procedure. Recommendations: Part 1 of this short version of the guideline presents recommendations for the screening, diagnosis and follow-up care of breast cancer. The importance of mammography for screening is confirmed in this updated version of the guideline and forms the basis for all screening. In addition to the conventional methods used to diagnose breast cancer, computed tomography (CT) is recommended for staging in women with a higher risk of recurrence. The follow-up concept includes suggested intervals between physical, ultrasound and mammography examinations, additional high-tech diagnostic procedures, and the determination of tumor markers for the evaluation of metastatic disease., Ziele: Das Ziel dieser offiziellen Leitlinie, die von der Deutschen Gesellschaft für Gynäkologie und Geburtshilfe (DGGG) und der Deutschen Krebsgesellschaft (DKG) publiziert und koordiniert wurde, ist es, die Früherkennung, Diagnostik, Therapie und Nachsorge des Mammakarzinoms zu optimieren. Methoden: Der Aktualisierungsprozess der S3-Leitlinie aus 2012 basierte zum einen auf der Adaptation identifizierter Quellleitlinien und zum anderen auf Evidenzübersichten, die nach Entwicklung von PICO-(Patients/Interventions/Control/Outcome-)Fragen, systematischer Recherche in Literaturdatenbanken sowie Selektion und Bewertung der gefundenen Literatur angefertigt wurden. In den interdisziplinären Arbeitsgruppen wurden auf dieser Grundlage Vorschläge für Empfehlungen und Statements erarbeitet, die im Rahmen von strukturierten Konsensusverfahren modifiziert und graduiert wurden. Empfehlungen: Der Teil 1 dieser Kurzversion der Leitlinie zeigt Empfehlungen zur Früherkennung, Diagnostik und Nachsorge des Mammakarzinoms: Der Stellenwert des Mammografie-Screenings wird in der aktualisierten Leitlinienversion bestätigt und bildet damit die Grundlage der Früherkennung. Neben den konventionellen Methoden der Karzinomdiagnostik wird die Computertomografie (CT) zum Staging bei höherem Rückfallrisiko empfohlen. Die Nachsorgekonzepte beinhalten Untersuchungsintervalle für die körperliche Untersuchung, Ultraschall und Mammografie, während weiterführende Gerätediagnostik und Tumormarkerbestimmungen bei der metastasierten Erkrankung Anwendung finden.
Published: 2018

33. Mutational spectrum in a worldwide study of 29,700 families with BRCA1 or BRCA2 mutations

Author: Fundações de Amparo à Pesquisa (Brasil), Research Foundation - Flanders, University of Helsinki, Sigrid Juselius Foundation, Dutch Cancer Society, Netherlands Organization for Scientific Research, Asociación Española Contra el Cáncer, Generalitat de Catalunya, Ministero della Salute, Istituto Oncologico Veneto, University of Tasmania, Australian Cancer Research Foundation, Ministry of Health and Welfare (South Korea), Charles University (Czech Republic), National Research Foundation Singapore, Russian Foundation for Basic Research, Istituto Toscano Tumori, Israel Cancer Association USA, Swedish Cancer Society, Foundation for Women's Cancer, University of Pittsburgh, Cancer Australia, American Cancer Society, The Ohio State University, National Institutes of Health (US), Cancer Research UK, European Commission, Canadian Institutes of Health Research, Department of Trade and Industry (UK), Susan G. Komen Foundation, Breast Cancer Research Foundation, Genome Canada, National Cancer Institute (US), Research Council of Lithuania, Cancer Association of South Africa, Consejo Nacional de Investigaciones Científicas y Técnicas (Argentina), Instituto de Salud Carlos III, Ministerio de Economía y Competitividad (España), Ministerio de Sanidad y Política Social (España), Associazione Italiana per la Ricerca sul Cancro, Fondazione Italiana per la Ricerca sul Cancro, Ministero dell'Istruzione, dell'Università e della Ricerca, Institut Pasteur, Fondazione Cenci Bolognetti, Greek Government, Pontificia Universidad Javeriana, Royal Marsden NHS Foundation Trust, Kansas State University, Fundación Mutua Madrileña, Ligue Nationale contre le Cancer (France), Georgetown University, Rebbeck, Timothy R., Friebel, Tara M., Friedman, Eitan, Hamann, Ute, Huo, Dezheng, Kwong, Ava, Olah, Edith, Olopade, Olufunmilayo I., Solano, Angela R., Teo, Soo-Hwamg, Thomassen, Mads, Mebirouk, Noura, Meijers-Heijboer, Hanne, Meindl, Alfons, Mensenkamp, Arjen R., Kruse, Torben A., Benitez, Javier, Mickys, Ugnius, Greene, Mark H., Miller, Austin, thomas, Abigail, Cook, Jackie, Montagna, Marco, Moysich, Kirsten B., Mulligan, Anna Marie, Musinsky, Jacob, Neuhausen, Susan L., Nevanlinna, Heli, Ngeow, Joanne, Berger, Andreas, Nguyen, Huu Phuc, Palmero, Edenir Inêz, Davidson, Rosemarie, Bonadona, Valérie, Schmutzler, Rita Katharina, Niederacher, Dieter, Nielsen, Henriette Roed, Nielsen, Finn Cilius, Nussbaum, Robert L., Offit, Kenneth, Öfverholm, Anna, Ong, Kai-ren, Berger, Raanan, Hoya, Miguel de la, Osorio, Ana, Konstantopoulou, Irene, Papi, Laura, Papp, Janos, Senter, Leigha, Kyung Park, Sue, Pasini, Barbara, Pedersen, Inge Sokilde, Peixoto, Ana, Peruga, Nina, Leeneer, Kim de, Peterlongo, Paolo, Blanco, Amie M., Thull, Darcy L., Pohl, Esther, Pradhan, Nisha, Prajzendanc, Karolina, Prieur, Fabienne, Shah, Payal D., Pujol, Pascal, Torres, Diana, Pauw, Antoine de, Radice, Paolo, Sharma, Priyanka, Side, Lucy E., Tischkowitz, Marc, Blazer, Kathleen R., Simard, Jacques, Singer, Christian F., Skytte, Anne-Bine, Slavin, Thomas P., Snape, Katie, Rashid, Muhammad Usman, Gronwald, Jacek, McGuffog, Lesley, Sobol, Hagay, Southey, Melissa, Tognazzo, Silvia, Steele, Linda, Blok, Marinus J., Steinemann, Doris, Toland, Amanda Ewart, Topka, Sabine, Delnatte, Capucine, Trainer, Alison H., Tung, Nadine, Hahnen, Eric, Asperen, Christi J. van, Hout, Annemieke H. van der, Korach, Jacob, Hogervorst, Frans B. L., Leslie, Goska, Kolk, Lizet E. van der, Luijt, Rob B. van der, Weitzel, Jeffrey N., Heetvelde, Mattias van, Varesco, Liliana, Varon-Mateeva, Raymonda, Vega, Ana, Villarreal-Garza, Cynthia, Hauke, Jan, Laitman, Yael, Wachenfeldt, Anna von, Ramus, Susan J., Walker, Lisa, Díez, Orland, Wang-Gohrke, Shan, Aalfs, Cora M., Wappenschmidt, Barbara, Weber, Bernhard H. F., Yannoukakos, Drakoulis, Yoon, Sook-Yee, Zanzottera, Cristina, Lasa, Adrian, Zidan, Jamal, HEBON, Lee, Min Hyuk, Bonanni, Bernardo, Zorn, Kristin K., Selkirk, Christina G. Hutten, Hulick, Peter J., Chenevix-Trench, Georgia, Abugattas, Julio, Spurdle, Amanda B., Antoniou, Antonis C., Lasset, Christine, Nathanson, Katherine L., Sukiennicki, Grzegorz, Adlard, Julian, Agata, Simona, Bradbury, Angela R., Henderson, Alex, Aittomäki, Kristiina, Andrews, Lesley, Andrulis, Irene L., Arason, Adalgeir, Arnold, Norbert, Couch, Fergus J., Ding, Yuan Chun, Arun, Branu K., Asseryanis, Ella, Auerbach, Leo, Azzollini, Jacopo, Brewer, Carole, Balmaña, Judith, Hentschel, Julia, Barile, Monica, Buecher, Bruno, Buys, Saundra S., Ditsch, Nina, Lázaro, Conxi, Caldés, Trinidad, Caliebe, Almuth, Caligo, Maria A., Campbell, Ian, Caputo, Sandrine M., Rantala, Johanna, Honisch, Ellen, Chiquette, Jocelyne, Chung, Wendy K., Domchek, Susan M., Claes, Kathleen B., Lee, Annette T., Collée, J. Margriet, Evans, D. Gareth, Dorfling, Cecilia M., Velázquez Pérez, Carolina, Dworniczak, Bernd, Eason, Jacqueline, Rhiem, Kerstin, Easton, Douglas F., Eeles, Ros, Sutter, Christian, Schmidt, Ane Y., Imyanitov, Evgeny N., Ehrencrona, Hans, Ejlertsen, Bent, EMBRACE, Engel, Christoph, Engert, Stefanie, Faivre, Laurence, Feliubadaló, Lidia, Robson, Mark, szabo, Csilla I., Tan, Yen Y., Fert Ferrer, Sandra, Barkardottir, Rosa B., Foretova, Lenka, Fowler, Jeffrey, Isaacs, Claudine, Frost, Debra, Galvão, Henrique C. R., Ganz, Patricia A., Garber, Judy, Gauthier-Villars, Marion, Teixeira, Manuel R., Gehrig, Andrea, Rodriguez, Gustavo C., Lester, Jenny, GEMO Study Collaborators, Gerdes, Anne-Marie, Gesta, Paul, Giannini, Giuseppe, Izat, Louise, Giraud, Sophie, Glendon, Gord, Terry, Mary Beth, Godwin, Andrew K., Izquierdo, Angel, Jakubowska, Anna, Lesueur, Fabienne, Rogers, Mark T., James, Paul, Janavicius, Ramunas, Jensen, Uffe Birk, John, Esther M., Vijai, Joseph, Gutierrez-Barrera, Angelica, Chan, T. L., Kaczmarek, Katarzyna, Karlan, Beth Y., Kast, Karin, Liljegren, Annelie, KConFab Investigators, Rudaitis, Vilius, Kim, Sung-Won, Lindor, Noralane M., Longy, Michel, Teulé, Alex, Loud, Jennifer T., Lu, Karen H., Goldgar, David E., Lubinski, Jan, Machackova, Eva, Barrowdale, Daniel, Rensburg, Elizabeth J. van, Manoukian, Siranoush, Mari, Véronique, Martínez-Bouzaz, Cristina, Parsons, Michael T., Matrai, Zoltan, Fundações de Amparo à Pesquisa (Brasil), Research Foundation - Flanders, University of Helsinki, Sigrid Juselius Foundation, Dutch Cancer Society, Netherlands Organization for Scientific Research, Asociación Española Contra el Cáncer, Generalitat de Catalunya, Ministero della Salute, Istituto Oncologico Veneto, University of Tasmania, Australian Cancer Research Foundation, Ministry of Health and Welfare (South Korea), Charles University (Czech Republic), National Research Foundation Singapore, Russian Foundation for Basic Research, Istituto Toscano Tumori, Israel Cancer Association USA, Swedish Cancer Society, Foundation for Women's Cancer, University of Pittsburgh, Cancer Australia, American Cancer Society, The Ohio State University, National Institutes of Health (US), Cancer Research UK, European Commission, Canadian Institutes of Health Research, Department of Trade and Industry (UK), Susan G. Komen Foundation, Breast Cancer Research Foundation, Genome Canada, National Cancer Institute (US), Research Council of Lithuania, Cancer Association of South Africa, Consejo Nacional de Investigaciones Científicas y Técnicas (Argentina), Instituto de Salud Carlos III, Ministerio de Economía y Competitividad (España), Ministerio de Sanidad y Política Social (España), Associazione Italiana per la Ricerca sul Cancro, Fondazione Italiana per la Ricerca sul Cancro, Ministero dell'Istruzione, dell'Università e della Ricerca, Institut Pasteur, Fondazione Cenci Bolognetti, Greek Government, Pontificia Universidad Javeriana, Royal Marsden NHS Foundation Trust, Kansas State University, Fundación Mutua Madrileña, Ligue Nationale contre le Cancer (France), Georgetown University, Rebbeck, Timothy R., Friebel, Tara M., Friedman, Eitan, Hamann, Ute, Huo, Dezheng, Kwong, Ava, Olah, Edith, Olopade, Olufunmilayo I., Solano, Angela R., Teo, Soo-Hwamg, Thomassen, Mads, Mebirouk, Noura, Meijers-Heijboer, Hanne, Meindl, Alfons, Mensenkamp, Arjen R., Kruse, Torben A., Benitez, Javier, Mickys, Ugnius, Greene, Mark H., Miller, Austin, thomas, Abigail, Cook, Jackie, Montagna, Marco, Moysich, Kirsten B., Mulligan, Anna Marie, Musinsky, Jacob, Neuhausen, Susan L., Nevanlinna, Heli, Ngeow, Joanne, Berger, Andreas, Nguyen, Huu Phuc, Palmero, Edenir Inêz, Davidson, Rosemarie, Bonadona, Valérie, Schmutzler, Rita Katharina, Niederacher, Dieter, Nielsen, Henriette Roed, Nielsen, Finn Cilius, Nussbaum, Robert L., Offit, Kenneth, Öfverholm, Anna, Ong, Kai-ren, Berger, Raanan, Hoya, Miguel de la, Osorio, Ana, Konstantopoulou, Irene, Papi, Laura, Papp, Janos, Senter, Leigha, Kyung Park, Sue, Pasini, Barbara, Pedersen, Inge Sokilde, Peixoto, Ana, Peruga, Nina, Leeneer, Kim de, Peterlongo, Paolo, Blanco, Amie M., Thull, Darcy L., Pohl, Esther, Pradhan, Nisha, Prajzendanc, Karolina, Prieur, Fabienne, Shah, Payal D., Pujol, Pascal, Torres, Diana, Pauw, Antoine de, Radice, Paolo, Sharma, Priyanka, Side, Lucy E., Tischkowitz, Marc, Blazer, Kathleen R., Simard, Jacques, Singer, Christian F., Skytte, Anne-Bine, Slavin, Thomas P., Snape, Katie, Rashid, Muhammad Usman, Gronwald, Jacek, McGuffog, Lesley, Sobol, Hagay, Southey, Melissa, Tognazzo, Silvia, Steele, Linda, Blok, Marinus J., Steinemann, Doris, Toland, Amanda Ewart, Topka, Sabine, Delnatte, Capucine, Trainer, Alison H., Tung, Nadine, Hahnen, Eric, Asperen, Christi J. van, Hout, Annemieke H. van der, Korach, Jacob, Hogervorst, Frans B. L., Leslie, Goska, Kolk, Lizet E. van der, Luijt, Rob B. van der, Weitzel, Jeffrey N., Heetvelde, Mattias van, Varesco, Liliana, Varon-Mateeva, Raymonda, Vega, Ana, Villarreal-Garza, Cynthia, Hauke, Jan, Laitman, Yael, Wachenfeldt, Anna von, Ramus, Susan J., Walker, Lisa, Díez, Orland, Wang-Gohrke, Shan, Aalfs, Cora M., Wappenschmidt, Barbara, Weber, Bernhard H. F., Yannoukakos, Drakoulis, Yoon, Sook-Yee, Zanzottera, Cristina, Lasa, Adrian, Zidan, Jamal, HEBON, Lee, Min Hyuk, Bonanni, Bernardo, Zorn, Kristin K., Selkirk, Christina G. Hutten, Hulick, Peter J., Chenevix-Trench, Georgia, Abugattas, Julio, Spurdle, Amanda B., Antoniou, Antonis C., Lasset, Christine, Nathanson, Katherine L., Sukiennicki, Grzegorz, Adlard, Julian, Agata, Simona, Bradbury, Angela R., Henderson, Alex, Aittomäki, Kristiina, Andrews, Lesley, Andrulis, Irene L., Arason, Adalgeir, Arnold, Norbert, Couch, Fergus J., Ding, Yuan Chun, Arun, Branu K., Asseryanis, Ella, Auerbach, Leo, Azzollini, Jacopo, Brewer, Carole, Balmaña, Judith, Hentschel, Julia, Barile, Monica, Buecher, Bruno, Buys, Saundra S., Ditsch, Nina, Lázaro, Conxi, Caldés, Trinidad, Caliebe, Almuth, Caligo, Maria A., Campbell, Ian, Caputo, Sandrine M., Rantala, Johanna, Honisch, Ellen, Chiquette, Jocelyne, Chung, Wendy K., Domchek, Susan M., Claes, Kathleen B., Lee, Annette T., Collée, J. Margriet, Evans, D. Gareth, Dorfling, Cecilia M., Velázquez Pérez, Carolina, Dworniczak, Bernd, Eason, Jacqueline, Rhiem, Kerstin, Easton, Douglas F., Eeles, Ros, Sutter, Christian, Schmidt, Ane Y., Imyanitov, Evgeny N., Ehrencrona, Hans, Ejlertsen, Bent, EMBRACE, Engel, Christoph, Engert, Stefanie, Faivre, Laurence, Feliubadaló, Lidia, Robson, Mark, szabo, Csilla I., Tan, Yen Y., Fert Ferrer, Sandra, Barkardottir, Rosa B., Foretova, Lenka, Fowler, Jeffrey, Isaacs, Claudine, Frost, Debra, Galvão, Henrique C. R., Ganz, Patricia A., Garber, Judy, Gauthier-Villars, Marion, Teixeira, Manuel R., Gehrig, Andrea, Rodriguez, Gustavo C., Lester, Jenny, GEMO Study Collaborators, Gerdes, Anne-Marie, Gesta, Paul, Giannini, Giuseppe, Izat, Louise, Giraud, Sophie, Glendon, Gord, Terry, Mary Beth, Godwin, Andrew K., Izquierdo, Angel, Jakubowska, Anna, Lesueur, Fabienne, Rogers, Mark T., James, Paul, Janavicius, Ramunas, Jensen, Uffe Birk, John, Esther M., Vijai, Joseph, Gutierrez-Barrera, Angelica, Chan, T. L., Kaczmarek, Katarzyna, Karlan, Beth Y., Kast, Karin, Liljegren, Annelie, KConFab Investigators, Rudaitis, Vilius, Kim, Sung-Won, Lindor, Noralane M., Longy, Michel, Teulé, Alex, Loud, Jennifer T., Lu, Karen H., Goldgar, David E., Lubinski, Jan, Machackova, Eva, Barrowdale, Daniel, Rensburg, Elizabeth J. van, Manoukian, Siranoush, Mari, Véronique, Martínez-Bouzaz, Cristina, Parsons, Michael T., and Matrai, Zoltan
Abstract: The prevalence and spectrum of germline mutations in BRCA1 and BRCA2 have been reported in single populations, with the majority of reports focused on White in Europe and North America. The Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) has assembled data on 18,435 families with BRCA1 mutations and 11,351 families with BRCA2 mutations ascertained from 69 centers in 49 countries on six continents. This study comprehensively describes the characteristics of the 1,650 unique BRCA1 and 1,731 unique BRCA2 deleterious (disease-associated) mutations identified in the CIMBA database. We observed substantial variation in mutation type and frequency by geographical region and race/ethnicity. In addition to known founder mutations, mutations of relatively high frequency were identified in specific racial/ethnic or geographic groups that may reflect founder mutations and which could be used in targeted (panel) first pass genotyping for specific populations. Knowledge of the population-specific mutational spectrum in BRCA1 and BRCA2 could inform efficient strategies for genetic testing and may justify a more broad-based oncogenetic testing in some populations.
Published: 2018

34. Evaluation of Polygenic Risk Scores for Breast and Ovarian Cancer Risk Prediction in BRCA1 and BRCA2 Mutation Carriers

Author: Kuchenbaecker, Karoline B., McGuffog, Lesley, Barrowdale, Daniel, Lee, Andrew, Soucy, Penny, Dennis, Joe, Domchek, Susan M., Robson, Mark, Spurdle, Amanda B., Ramus, Susan J., Mavaddat, Nasim, Terry, Mary Beth, Neuhausen, Susan L., Schmutzler, Rita Katharina, Simard, Jacques, Pharoah, Paul D. P., Offit, Kenneth, Couch, Fergus J., Chenevix-Trench, Georgia, Easton, Douglas F., Antoniou, Antonis C., Oosterwijk, Jan, Targeted Gynaecologic Oncology (TARGON), and Damage and Repair in Cancer Development and Cancer Treatment (DARE)
Subjects: WIDE ASSOCIATION ANALYSIS, endocrine system diseases, IDENTIFICATION, MORTALITY, SUSCEPTIBILITY ALLELES, LOCUS, WOMEN, MODIFIERS, COHORT, FUNCTIONAL VARIANTS, skin and connective tissue diseases, EARLY BILATERAL OOPHORECTOMY
Abstract: Background: Genome-wide association studies (GWAS) have identified 94 common single-nucleotide polymorphisms (SNPs) associated with breast cancer (BC) risk and 18 associated with ovarian cancer (OC) risk. Several of these are also associated with risk of BC or OC for women who carry a pathogenic mutation in the high-risk BC and OC genes BRCA1 or BRCA2. The combined effects of these variants on BC or OC risk for BRCA1 and BRCA2 mutation carriers have not yet been assessed while their clinical management could benefit from improved personalized risk estimates. Methods: We constructed polygenic risk scores (PRS) using BC and OC susceptibility SNPs identified through population-based GWAS: for BC (overall, estrogen receptor [ER]-positive, and ER-negative) and for OC. Using data from 15 252 female BRCA1 and 8211 BRCA2 carriers, the association of each PRS with BC or OC risk was evaluated using a weighted cohort approach, with time to diagnosis as the outcome and estimation of the hazard ratios (HRs) per standard deviation increase in the PRS. Results: The PRS for ER-negative BC displayed the strongest association with BC risk in BRCA1 carriers (HR = 1.27, 95% confidence interval [CI] = 1.23 to 1.31, P = 8.2 x 10(53)). In BRCA2 carriers, the strongest association with BC risk was seen for the overall BC PRS (HR = 1.22, 95% CI = 1.17 to 1.28, P = 7.2 x 10(-20)). The OC PRS was strongly associated with OC risk for both BRCA1 and BRCA2 carriers. These translate to differences in absolute risks (more than 10% in each case) between the top and bottom deciles of the PRS distribution; for example, the OC risk was 6% by age 80 years for BRCA2 carriers at the 10th percentile of the OC PRS compared with 19% risk for those at the 90th percentile of PRS. Conclusions: BC and OC PRS are predictive of cancer risk in BRCA1 and BRCA2 carriers. Incorporation of the PRS into risk prediction models has promise to better inform decisions on cancer risk management.
Published: 2017

35. Identification of 12 new susceptibility loci for different histotypes of epithelial ovarian cancer

Author: Phelan, Catherine M. Kuchenbaecker, Karoline B. Tyrer, Jonathan P. Kar, Siddhartha P. Lawrenson, Kate Winham, Stacey J. and Dennis, Joe Pirie, Ailith Riggan, Marjorie J. Chornokur, Ganna Earp, Madalene A. Lyra, Jr., Paulo C. Lee, Janet M. and Coetzee, Simon Beesley, Jonathan McGuffog, Lesley Soucy, Penny Dicks, Ed Lee, Andrew Barrowdale, Daniel and Lecarpentier, Julie Leslie, Goska Aalfs, Cora M. Aben, Katja K. H. Adams, Marcia Adlard, Julian Andrulis, Irene L. and Anton-Culver, Hoda Antonenkova, Natalia Aravantinos, Gerasimos and Arnold, Norbert Arun, Banu K. Arver, Brita Azzollini, Jacopo Balmana, Judith Banerjee, Susana N. Barjhoux, Laure and Barkardottir, Rosa B. Bean, Yukie Beckmann, Matthias W. and Beeghly-Fadiel, Alicia Benitez, Javier Bermisheva, Marina and Bernardini, Marcus Q. Birrer, Michael J. Bjorge, Line Black, Amanda Blankstein, Kenneth Blok, Marinus J. Bodelon, Clara and Bogdanova, Natalia Bojesen, Anders Bonanni, Bernardo and Borg, Ake Bradbury, Angela R. Brenton, James D. Brewer, Carole Brinton, Louise Broberg, Per Brooks-Wilson, Angela and Bruinsma, Fiona Brunet, Joan Buecher, Bruno Butzow, Ralf and Buys, Saundra S. Caldes, Trinidad Caligo, Maria A. and Campbell, Ian Cannioto, Rikki Carney, Michael E. Cescon, Terence Chan, Salina B. Chang-Claude, Jenny Chanock, Stephen and Chen, Xiao Qing Chiew, Yoke-Eng Chiquette, Jocelyne and Chung, Wendy K. Claes, Kathleen B. M. Conner, Thomas Cook, Linda S. Cook, Jackie Cramer, Daniel W. Cunningham, Julie M. and D'Aloisio, Aimee A. Daly, Mary B. Damiola, Francesca and Damirovna, Sakaeva Dina Dansonka-Mieszkowska, Agnieszka Dao, Fanny Davidson, Rosemarie DeFazio, Anna Delnatte, Capucine and Doheny, Kimberly F. Diez, Orland Ding, Yuan Chun and Doherty, Jennifer Anne Domchek, Susan M. Dorfling, Cecilia M. and Dork, Thilo Dossus, Laure Duran, Mercedes Durst, Matthias Dworniczak, Bernd Eccles, Diana Edwards, Todd and Eeles, Ros Eilber, Ursula Ejlertsen, Bent Ekici, Arif B. and Ellis, Steve Elvira, Mingajeva Eng, Kevin H. Engel, Christoph Evans, D. Gareth Fasching, Peter A. Ferguson, Sarah Ferrer, Sandra Fert Flanagan, James M. Fogarty, Zachary C. Fortner, Renee T. Fostira, Florentia Foulkes, William D. Fountzilas, George Fridley, Brooke L. Friebel, Tara M. Friedman, Eitan Frost, Debra Ganz, Patricia A. and Garber, Judy Garcia, Maria J. Garcia-Barberan, Vanesa and Gehrig, Andrea Gentry-Maharaj, Aleksandra Gerdes, Anne-Marie and Giles, Graham G. Glasspool, Rosalind Glendon, Gord Godwin, Andrew K. Goldgar, David E. Goranova, Teodora Gore, Martin and Greene, Mark H. Gronwald, Jacek Gruber, Stephen Hahnen, Eric Haiman, Christopher A. Hakansson, Niclas Hamann, Ute and Hansen, Thomas V. O. Harrington, Patricia A. Harris, Holly R. Hauke, Jan Hein, Alexander Henderson, Alex and Hildebrandt, Michelle A. T. Hillemanns, Peter Hodgson, Shirley and Hogdall, Claus K. Hogdall, Estrid Hogervorst, Frans B. L. and Holland, Helene Hooning, Maartje J. Hosking, Karen and Huang, Ruea-Yea Hulick, Peter J. Hung, Jillian Hunter, David J. Huntsman, David G. Huzarski, Tomasz Imyanitov, Evgeny N. and Isaacs, Claudine Iversen, Edwin S. Izatt, Louise and Izquierdo, Angel Jakubowska, Anna James, Paul Janavicius, Ramunas Jernetz, Mats Jensen, Allan Jensen, Uffe Birk and John, Esther M. Johnatty, Sharon Jones, Michael E. Kannisto, Paivi Karlan, Beth Y. Karnezis, Anthony Kast, Karin and Kennedy, Catherine J. Khusnutdinova, Elza Kiemeney, Lambertus A. and Kiiski, Johanna I. Kim, Sung-Won Kjaer, Susanne K. and Kobel, Martin Kopperud, Reidun K. Kruse, Torben A. and Kupryjanczyk, Jolanta Kwong, Ava Laitman, Yael Lambrechts, Diether Larranaga, Nerea Larson, Melissa C. Lazaro, Conxi and Le, Nhu D. Le Marchand, Loic Lee, Jong Won Lele, Shashikant B. Leminen, Arto Leroux, Dominique Lester, Jenny and Lesueur, Fabienne Levine, Douglas A. Liang, Dong and Liebrich, Clemens Lilyquist, Jenna Lipworth, Loren and Lissowska, Jolanta Lu, Karen H. Lubinski, Jan Luccarini, Craig Lundvall, Lene Mai, Phuong L. Mendoza-Fandino, Gustavo and Manoukian, Siranoush Massuger, Leon F. A. G. May, Taymaa and Mazoyer, Sylvie McAlpine, Jessica N. McGuire, Valerie and McLaughlin, John R. McNeish, Iain Meijers-Heijboer, Hanne and Meindl, Alfons Menon, Usha Mensenkamp, Arjen R. Merritt, Melissa A. Milne, Roger L. Mitchell, Gillian Modugno, Francesmary Moes-Sosnowska, Joanna Moffitt, Melissa and Montagna, Marco Moysich, Kirsten B. Mulligan, Anna Marie and Musinsky, Jacob Nathanson, Katherine L. Nedergaard, Lotte and Ness, Roberta B. Neuhausen, Susan L. Nevanlinna, Heli and Niederacher, Dieter Nussbaum, Robert L. Odunsi, Kunle Olah, Edith Olopade, Olufunmilayo I. Olsson, Hakan Olswold, Curtis and O'Malley, David M. Ong, Kai-ren Onland-Moret, N. Charlotte and Orr, Nicholas Orsulic, Sandra Osorio, Ana Palli, Domenico Papi, Laura Park-Simon, Tjoung-Won Paul, James and Pearce, Celeste L. Pedersen, Inge Sokilde Peeters, Petra H. M. and Peissel, Bernard Peixoto, Ana Pejovic, Tanja Pelttari, Liisa M. Permuth, Jennifer B. Peterlongo, Paolo Pezzani, Lidia Pfeiler, Georg Phillips, Kelly-Anne Piedmonte, Marion and Pike, Malcolm C. Piskorz, Anna M. Poblete, Samantha R. and Pocza, Timea Poole, Elizabeth M. Poppe, Bruce Porteous, Mary E. Prieur, Fabienne Prokofyeva, Darya Pugh, Elizabeth and Pujana, Miquel Angel Pujol, Pascal Radice, Paolo Rantala, Johanna Rappaport-Fuerhauser, Christine Rennert, Gad Rhiem, Kerstin Rice, Patricia Richardson, Andrea Robson, Mark and Rodriguez, Gustavo C. Rodriguez-Antona, Cristina Romm, Jane and Rookus, Matti A. Rossing, Mary Anne Rothstein, Joseph H. and Rudolph, Anja Runnebaum, Ingo B. Salvesen, Helga B. Sandler, Dale P. Schoemaker, Minouk J. Senter, Leigha Setiawan, V. Wendy Severi, Gianluca Sharma, Priyanka Shelford, Tameka and Siddiqui, Nadeem Side, Lucy E. Sieh, Weiva Singer, Christian F. Sobol, Hagay Song, Honglin Southey, Melissa C. and Spurdle, Amanda B. Stadler, Zsofia Steinemann, Doris and Stoppa-Lyonnet, Dominique Sucheston-Campbell, Lara E. and Sukiennicki, Grzegorz Sutphen, Rebecca Sutter, Christian and Swerdlow, Anthony J. Szabo, Csilla I. Szafron, Lukasz Tan, Yen Y. Taylor, Jack A. Tea, Muy-Kheng Teixeira, Manuel R. and Teo, Soo-Hwang Terry, Kathryn L. Thompson, Pamela J. and Thomsen, Liv Cecilie Vestrheim Thull, Darcy L. Tihomirova, Laima and Tinker, Anna V. Tischkowitz, Marc Tognazzo, Silvia and Toland, Amanda Ewart Tone, Alicia Trabert, Britton Travis, Ruth C. Trichopoulou, Antonia Tung, Nadine Tworoger, Shelley S. Van Altena, Anne M. Van den Berg, David van der Hout, Annemarie H. van der Luijt, Rob B. Van Heetvelde, Mattias and Van Nieuwenhuysen, Els Van Rensburg, Elizabeth J. and Vanderstichele, Adriaan Varon-Mateeva, Raymonda Vega, Ana and Edwards, Digna Velez Vergote, Ignace Vierkant, Robert A. and Vijai, Joseph Vratimos, Athanassios Walker, Lisa Walsh, Christine Wand, Dorothea Wang-Gohrke, Shan Wappenschmidt, Barbara Webb, Penelope M. Weinberg, Clarice R. Weitzel, Jeffrey N. Wentzensen, Nicolas Whittemore, Alice S. Wijnen, Juul T. Wilkens, Lynne R. Wolk, Alicja Woo, Michelle Wu, Xifeng Wu, Anna H. Yang, Hannah Yannoukakos, Drakoulis and Ziogas, Argyrios Zorn, Kristin K. Narod, Steven A. Easton, Douglas F. Amos, Christopher I. Schildkraut, Joellen M. and Ramus, Susan J. Ottini, Laura Goodman, Marc T. Park-, Sue K. and Kelemen, Linda E. Risch, Harvey A. Thomassen, Mads and Offit, Kenneth Simard, Jacques Schmutzler, Rita Katharina and Hazelett, Dennis Monteiro, Alvaro N. Couch, Fergus J. and Berchuck, Andrew Chenevix-Trench, Georgia Goode, Ellen L. and Sellers, Thomas A. Gayther, Simon A. Antoniou, Antonis C. and Pharoah, Paul D. P. AOCS Study Grp EMEMBRACE Study GEMO Study Collaborators HEBON Study KConFab Investigators OPAL Study Grp
Subjects: endocrine system diseases, female genital diseases and pregnancy complications
Abstract: To identify common alleles associated with different histotypes of epithelial ovarian cancer (EOC), we pooled data from multiple genome-wide genotyping projects totaling 25,509 EOC cases and 40,941 controls. We identified nine new susceptibility loci for different EOC histotypes: six for serous EOC histotypes (3q28, 4q32.3, 8q21.11, 10q24.33, 18q11.2 and 22q12.1), two for mucinous EOC (3q22.3 and 9q31.1) and one for endometrioid EOC (5q12.3). We then performed meta-analysis on the results for high-grade serous ovarian cancer with the results from analysis of 31,448 BRCA1 and BRCA2 mutation carriers, including 3,887 mutation carriers with EOC. This identified three additional susceptibility loci at 2q13, 8q24.1 and 12q24.31. Integrated analyses of genes and regulatory biofeatures at each locus predicted candidate susceptibility genes, including OBFC1, a new candidate susceptibility gene for low-grade and borderline serous EOC.
Published: 2017

36. Correction: Evaluation of copy-number variants as modifiers of breast and ovarian cancer risk for BRCA1 pathogenic variant carriers

Author: Walker, Logan C., Marquart, Louise, Pearson, John F., Wiggins, George A. R., O’Mara, Tracy A., Parsons, Michael T., Barrowdale, Daniel, McGuffog, Lesley, Dennis, Joe, Benitez, Javier, Slavin, Thomas P., Radice, Paolo, Frost, Debra, Godwin, Andrew K., Meindl, Alfons, Schmutzler, Rita Katharina, Isaacs, Claudine, Peshkin, Beth N., Caldes, Trinidad, Hogervorst, Frans B. L., Lazaro, Conxi, Jakubowska, Anna, Montagna, Marco, Chen, Xiaoqing, Offit, Kenneth, Hulick, Peter J., Andrulis, Irene L., Lindblom, Annika, Nussbaum, Robert L., Nathanson, Katherine L., Chenevix-Trench, Georgia, Antoniou, Antonis C., Couch, Fergus J., and Spurdle, Amanda B.
Subjects: Adult, Glutamate Carboxypeptidase II, Ovarian Neoplasms, Genetics, Heterozygote, Genes, Modifier, DNA Copy Number Variations, BRCA1 Protein, Pregnancy-Specific beta 1-Glycoproteins, Correction, Breast Neoplasms, Biology, medicine.disease, Human genetics, DNA-Binding Proteins, Transcription Factors, TFII, medicine, Humans, Female, Aryl Hydrocarbon Hydroxylases, Copy-number variation, Cytochrome P450 Family 2, Ovarian cancer, Genetics (clinical)
Abstract: Genome-wide studies of patients carrying pathogenic variants (mutations) in BRCA1 or BRCA2 have reported strong associations between single-nucleotide polymorphisms (SNPs) and cancer risk. To conduct the first genome-wide association analysis of copy-number variants (CNVs) with breast or ovarian cancer risk in a cohort of 2500 BRCA1 pathogenic variant carriers, CNV discovery was performed using multiple calling algorithms and Illumina 610k SNP array data from a previously published genome-wide association study. Our analysis, which focused on functionally disruptive genomic deletions overlapping gene regions, identified a number of loci associated with risk of breast or ovarian cancer for BRCA1 pathogenic variant carriers. Despite only including putative deletions called by at least two or more algorithms, detection of selected CNVs by ancillary molecular technologies only confirmed 40% of predicted common (1% allele frequency) variants. These include four loci that were associated (unadjusted P0.05) with breast cancer (GTF2H2, ZNF385B, NAALADL2 and PSG5), and two loci associated with ovarian cancer (CYP2A7 and OR2A1). An interesting finding from this study was an association of a validated CNV deletion at the CYP2A7 locus (19q13.2) with decreased ovarian cancer risk (relative risk=0.50, P=0.007). Genomic analysis found this deletion coincides with a region displaying strong regulatory potential in ovarian tissue, but not in breast epithelial cells. This study highlighted the need to verify CNVs in vitro, but also provides evidence that experimentally validated CNVs (with plausible biological consequences) can modify risk of breast or ovarian cancer in BRCA1 pathogenic variant carriers.
Published: 2018

37. Association of breast cancer risk in BRCA1 and BRCA2 mutation carriers with genetic variants showing differential allelic expression

Author: University of Helsinki, Medicum, University of Helsinki, Department of Obstetrics and Gynecology, Hamdi, Yosr, Soucy, Penny, Kuchenbaeker, Karoline B., Pastinen, Tomi, Droit, Arnaud, Lemacon, Audrey, Adlard, Julian, Aittomäki, Kristiina, Andrulis, Irene L., Arason, Adalgeir, Arnold, Norbert, Arun, Banu K., Azzollini, Jacopo, Bane, Anita, Barjhoux, Laure, Barrowdale, Daniel, Benitez, Javier, Berthet, Pascaline, Blok, Marinus J., Bobolis, Kristie, Bonadona, Valerie, Bonanni, Bernardo, Bradbury, Angela R., Brewer, Carole, Buecher, Bruno, Buys, Saundra S., Caligo, Maria A., Chiquette, Jocelyne, Chung, Wendy K., Claes, Kathleen B. M., Daly, Mary B., Damiola, Francesca, Davidson, Rosemarie, De la Hoya, Miguel, De Leeneer, Kim, Diez, Orland, Ding, Yuan Chun, Dolcetti, Riccardo, Domchek, Susan M., Dorfling, Cecilia M., Eccles, Diana, Eeles, Ros, Einbeigi, Zakaria, Ejlertsen, Bent, Engel, Christoph, Evans, D. Gareth, Feliubadalo, Lidia, Foretova, Lenka, Fostira, Florentia, Foulkes, William D., Fountzilas, George, Friedman, Eitan, Frost, Debra, Ganschow, Pamela, Ganz, Patricia A., Garber, Judy, Gayther, Simon A., Gerdes, Anne-Marie, Glendon, Gord, Godwin, Andrew K., Goldgar, David E., Greene, Mark H., Gronwald, Jacek, Hahnen, Eric, Hamann, Ute, Hansen, Thomas V. O., Hart, Steven, Hays, John L., Hogervorst, Frans B. L., Hulick, Peter J., Imyanitov, Evgeny N., Isaacs, Claudine, Izatt, Louise, Jakubowska, Anna, James, Paul, Janavicius, Ramunas, Jensen, Uffe Birk, John, Esther M., Joseph, Vijai, Just, Walter, Kaczmarek, Katarzyna, Karlan, Beth Y., Kets, Carolien M., Kirk, Judy, Kriege, Mieke, Laitman, Yael, Laurent, Maite, Lazaro, Conxi, Leslie, Goska, Lester, Jenny, Lesueur, Fabienne, Liljegren, Annelie, Loman, Niklas, Loud, Jennifer T., Manoukian, Siranoush, Mariani, Milena, Mazoyer, Sylvie, McGuffog, Lesley, Meijers-Heijboer, Hanne E. J., Meindl, Alfons, Miller, Austin, Montagna, Marco, Mulligan, Anna Marie, Nathanson, Katherine L., Neuhausen, Susan L., Nevanlinna, Heli, Nussbaum, Robert L., Olah, Edith, Olopade, Olufunmilayo I., Ong, Kai-ren, Oosterwijk, Jan C., Osorio, Ana, Papi, Laura, Park, Sue Kyung, Pedersen, Inge Sokilde, Peissel, Bernard, Segura, Pedro Perez, Peterlongo, Paolo, Phelan, Catherine M., Radice, Paolo, Rantala, Johanna, Rappaport-Fuerhauser, Christine, Rennert, Gad, Richardson, Andrea, Robson, Mark, Rodriguez, Gustavo C., Rookus, Matti A., Schmutzler, Rita Katharina, Sevenet, Nicolas, Shah, Payal D., Singer, Christian F., Slavin, Thomas P., Snape, Katie, Sokolowska, Johanna, Sonderstrup, Ida Marie Heeholm, Southey, Melissa, Spurdle, Amanda B., Stadler, Zsofia, Stoppa-Lyonnet, Dominique, Sukiennicki, Grzegorz, Sutter, Christian, Tan, Yen, Tea, Muy-Kheng, Teixeira, Manuel R., Teule, Alex, Teo, Soo-Hwang, Terry, Mary Beth, Thomassen, Mads, Tihomirova, Laima, Tischkowitz, Marc, Tognazzo, Silvia, Toland, Amanda Ewart, Tung, Nadine, van den Ouweland, Ans M. W., van der Luijt, Rob B., van Engelen, Klaartje, van Rensburg, Elizabeth J., Varon-Mateeva, Raymonda, Wappenschmidt, Barbara, Wijnen, Juul T., Rebbeck, Timothy, Chenevix-Trench, Georgia, Offit, Kenneth, Couch, Fergus J., Nord, Silje, Easton, Douglas F., Antoniou, Antonis C., Simard, Jacques, EMBRACE, GEMO Study Collaborators, HEBON, KConFab Investigators, University of Helsinki, Medicum, University of Helsinki, Department of Obstetrics and Gynecology, Hamdi, Yosr, Soucy, Penny, Kuchenbaeker, Karoline B., Pastinen, Tomi, Droit, Arnaud, Lemacon, Audrey, Adlard, Julian, Aittomäki, Kristiina, Andrulis, Irene L., Arason, Adalgeir, Arnold, Norbert, Arun, Banu K., Azzollini, Jacopo, Bane, Anita, Barjhoux, Laure, Barrowdale, Daniel, Benitez, Javier, Berthet, Pascaline, Blok, Marinus J., Bobolis, Kristie, Bonadona, Valerie, Bonanni, Bernardo, Bradbury, Angela R., Brewer, Carole, Buecher, Bruno, Buys, Saundra S., Caligo, Maria A., Chiquette, Jocelyne, Chung, Wendy K., Claes, Kathleen B. M., Daly, Mary B., Damiola, Francesca, Davidson, Rosemarie, De la Hoya, Miguel, De Leeneer, Kim, Diez, Orland, Ding, Yuan Chun, Dolcetti, Riccardo, Domchek, Susan M., Dorfling, Cecilia M., Eccles, Diana, Eeles, Ros, Einbeigi, Zakaria, Ejlertsen, Bent, Engel, Christoph, Evans, D. Gareth, Feliubadalo, Lidia, Foretova, Lenka, Fostira, Florentia, Foulkes, William D., Fountzilas, George, Friedman, Eitan, Frost, Debra, Ganschow, Pamela, Ganz, Patricia A., Garber, Judy, Gayther, Simon A., Gerdes, Anne-Marie, Glendon, Gord, Godwin, Andrew K., Goldgar, David E., Greene, Mark H., Gronwald, Jacek, Hahnen, Eric, Hamann, Ute, Hansen, Thomas V. O., Hart, Steven, Hays, John L., Hogervorst, Frans B. L., Hulick, Peter J., Imyanitov, Evgeny N., Isaacs, Claudine, Izatt, Louise, Jakubowska, Anna, James, Paul, Janavicius, Ramunas, Jensen, Uffe Birk, John, Esther M., Joseph, Vijai, Just, Walter, Kaczmarek, Katarzyna, Karlan, Beth Y., Kets, Carolien M., Kirk, Judy, Kriege, Mieke, Laitman, Yael, Laurent, Maite, Lazaro, Conxi, Leslie, Goska, Lester, Jenny, Lesueur, Fabienne, Liljegren, Annelie, Loman, Niklas, Loud, Jennifer T., Manoukian, Siranoush, Mariani, Milena, Mazoyer, Sylvie, McGuffog, Lesley, Meijers-Heijboer, Hanne E. J., Meindl, Alfons, Miller, Austin, Montagna, Marco, Mulligan, Anna Marie, Nathanson, Katherine L., Neuhausen, Susan L., Nevanlinna, Heli, Nussbaum, Robert L., Olah, Edith, Olopade, Olufunmilayo I., Ong, Kai-ren, Oosterwijk, Jan C., Osorio, Ana, Papi, Laura, Park, Sue Kyung, Pedersen, Inge Sokilde, Peissel, Bernard, Segura, Pedro Perez, Peterlongo, Paolo, Phelan, Catherine M., Radice, Paolo, Rantala, Johanna, Rappaport-Fuerhauser, Christine, Rennert, Gad, Richardson, Andrea, Robson, Mark, Rodriguez, Gustavo C., Rookus, Matti A., Schmutzler, Rita Katharina, Sevenet, Nicolas, Shah, Payal D., Singer, Christian F., Slavin, Thomas P., Snape, Katie, Sokolowska, Johanna, Sonderstrup, Ida Marie Heeholm, Southey, Melissa, Spurdle, Amanda B., Stadler, Zsofia, Stoppa-Lyonnet, Dominique, Sukiennicki, Grzegorz, Sutter, Christian, Tan, Yen, Tea, Muy-Kheng, Teixeira, Manuel R., Teule, Alex, Teo, Soo-Hwang, Terry, Mary Beth, Thomassen, Mads, Tihomirova, Laima, Tischkowitz, Marc, Tognazzo, Silvia, Toland, Amanda Ewart, Tung, Nadine, van den Ouweland, Ans M. W., van der Luijt, Rob B., van Engelen, Klaartje, van Rensburg, Elizabeth J., Varon-Mateeva, Raymonda, Wappenschmidt, Barbara, Wijnen, Juul T., Rebbeck, Timothy, Chenevix-Trench, Georgia, Offit, Kenneth, Couch, Fergus J., Nord, Silje, Easton, Douglas F., Antoniou, Antonis C., Simard, Jacques, EMBRACE, GEMO Study Collaborators, HEBON, and KConFab Investigators
Abstract: Cis-acting regulatory SNPs resulting in differential allelic expression (DAE) may, in part, explain the underlying phenotypic variation associated with many complex diseases. To investigate whether common variants associated with DAE were involved in breast cancer susceptibility among BRCA1 and BRCA2 mutation carriers, a list of 175 genes was developed based of their involvement in cancer-related pathways. Using data from a genome-wide map of SNPs associated with allelic expression, we assessed the association of similar to 320 SNPs located in the vicinity of these genes with breast and ovarian cancer risks in 15,252 BRCA1 and 8211 BRCA2 mutation carriers ascertained from 54 studies participating in the Consortium of Investigators of Modifiers of BRCA1/2. We identified a region on 11q22.3 that is significantly associated with breast cancer risk in BRCA1 mutation carriers (most significant SNP rs228595 p = 7 x 10(-6)). This association was absent in BRCA2 carriers (p = 0.57). The 11q22.3 region notably encompasses genes such as ACAT1, NPAT, and ATM. Expression quantitative trait loci associations were observed in both normal breast and tumors across this region, namely for ACAT1, ATM, and other genes. In silico analysis revealed some overlap between top risk-associated SNPs and relevant biological features in mammary cell data, which suggests potential functional significance. We identified 11q22.3 as a new modifier locus in BRCA1 carriers. Replication in larger studies using estrogen receptor (ER)-negative or triple-negative (i.e., ER-, progesterone receptor-, and HER2-negative) cases could therefore be helpful to confirm the association of this locus with breast cancer risk.
Published: 2017

38. Evaluation of copy-number variants as modifiers of breast and ovarian cancer risk for BRCA1 pathogenic variant carriers

Author: Walker, Logan, Marquart, Louise, Pearson, John, Wiggins, George, O'Mara, Tracy, Parsons, Michael T., Barrowdale, Daniel, McGuffog, Lesley, Dennis, Joe, Benitez, Javier, Slavin, Thomas P., Radice, Paolo, Frost, Debra, Godwin, Andrew K., Meindl, Alfons, Schmutzler, Rita Katharina, Isaacs, Claudine, Peshkin, Beth N., Caldes, Trinidad, Hogervorst, Frans B. L., Lazaro, Conxi, Jakubowska, Anna, Montagna, Marco, Chen, Xiaoqing, Offit, Kenneth, Hulick, Peter J., Andrulis, Irene L., Lindblom, Annika, Nussbaum, Robert L., Nathanson, Katherine L., Chenevix-Trench, Georgia, Antoniou, Antonis C., Couch, Fergus J., Spurdle, Amanda B., Walker, Logan, Marquart, Louise, Pearson, John, Wiggins, George, O'Mara, Tracy, Parsons, Michael T., Barrowdale, Daniel, McGuffog, Lesley, Dennis, Joe, Benitez, Javier, Slavin, Thomas P., Radice, Paolo, Frost, Debra, Godwin, Andrew K., Meindl, Alfons, Schmutzler, Rita Katharina, Isaacs, Claudine, Peshkin, Beth N., Caldes, Trinidad, Hogervorst, Frans B. L., Lazaro, Conxi, Jakubowska, Anna, Montagna, Marco, Chen, Xiaoqing, Offit, Kenneth, Hulick, Peter J., Andrulis, Irene L., Lindblom, Annika, Nussbaum, Robert L., Nathanson, Katherine L., Chenevix-Trench, Georgia, Antoniou, Antonis C., Couch, Fergus J., and Spurdle, Amanda B.
Abstract: Genome-wide studies of patients carrying pathogenic variants (mutations) in BRCA1 or BRCA2 have reported strong associations between single-nucleotide polymorphisms (SNPs) and cancer risk. To conduct the first genome-wide association analysis of copynumber variants (CNVs) with breast or ovarian cancer risk in a cohort of 2500 BRCA1 pathogenic variant carriers, CNV discovery was performed using multiple calling algorithms and Illumina 610k SNP array data from a previously published genome-wide association study. Our analysis, which focused on functionally disruptive genomic deletions overlapping gene regions, identified a number of loci associated with risk of breast or ovarian cancer for BRCA1 pathogenic variant carriers. Despite only including putative deletions called by at least two or more algorithms, detection of selected CNVs by ancillary molecular technologies only confirmed 40% of predicted common (>1% allele frequency) variants. These include four loci that were associated (unadjusted P<0.05) with breast cancer (GTF2H2, ZNF385B, NAALADL2 and PSG5), and two loci associated with ovarian cancer (CYP2A7 and OR2A1). An interesting finding from this study was an association of a validated CNV deletion at the CYP2A7 locus (19q13.2) with decreased ovarian cancer risk (relative risk=0.50, P=0.007). Genomic analysis found this deletion coincides with a region displaying strong regulatory potential in ovarian tissue, but not in breast epithelial cells. This study highlighted the need to verify CNVs in vitro, but also provides evidence that experimentally validated CNVs (with plausible biological consequences) can modify risk of breast or ovarian cancer in BRCA1 pathogenic variant carriers.
Published: 2017

39. Identification of 12 new susceptibility loci for different histotypes of epithelial ovarian cancer

Author: Phelan, Catherine M., Kuchenbaecker, Karoline B., Tyrer, Jonathan P., Kar, Siddhartha P., Lawrenson, Kate, Winham, Stacey J., Dennis, Joe, Pirie, Ailith, Riggan, Marjorie J., Chornokur, Ganna, Earp, Madalene A., Lyra, Paulo C., Jr., Lee, Janet M., Coetzee, Simon, Beesley, Jonathan, McGuffog, Lesley, Soucy, Penny, Dicks, Ed, Lee, Andrew, Barrowdale, Daniel, Lecarpentier, Julie, Leslie, Goska, Aalfs, Cora M., Aben, Katja K. H., Adams, Marcia, Adlard, Julian, Andrulis, Irene L., Anton-Culver, Hoda, Antonenkova, Natalia, Aravantinos, Gerasimos, Arnold, Norbert, Arun, Banu K., Arver, Brita, Azzollini, Jacopo, Balmana, Judith, Banerjee, Susana N., Barjhoux, Laure, Barkardottir, Rosa B., Bean, Yukie, Beckmann, Matthias W., Beeghly-Fadiel, Alicia, Benitez, Javier, Bermisheva, Marina, Bernardini, Marcus Q., Birrer, Michael J., Bjorge, Line, Black, Amanda, Blankstein, Kenneth, Blok, Marinus J., Bodelon, Clara, Bogdanova, Natalia, Bojesen, Anders, Bonanni, Bernardo, Borg, Ake, Bradbury, Angela R., Brenton, James D., Brewer, Carole, Brinton, Louise, Broberg, Per, Brooks-Wilson, Angela, Bruinsma, Fiona, Brunet, Joan, Buecher, Bruno, Butzow, Ralf, Buys, Saundra S., Caldes, Trinidad, Caligo, Maria A., Campbell, Ian, Cannioto, Rikki, Carney, Michael E., Cescon, Terence, Chan, Salina B., Chang-Claude, Jenny, Chanock, Stephen, Chen, Xiao Qing, Chiew, Yoke-Eng, Chiquette, Jocelyne, Chung, Wendy K., Claes, Kathleen B. M., Conner, Thomas, Cook, Linda S., Cook, Jackie, Cramer, Daniel W., Cunningham, Julie M., D'Aloisio, Aimee A., Daly, Mary B., Damiola, Francesca, Damirovna, Sakaeva Dina, Dansonka-Mieszkowska, Agnieszka, Dao, Fanny, Davidson, Rosemarie, DeFazio, Anna, Delnatte, Capucine, Doheny, Kimberly F., Diez, Orland, Ding, Yuan Chun, Doherty, Jennifer Anne, Domchek, Susan M., Dorfling, Cecilia M., Dork, Thilo, Dossus, Laure, Duran, Mercedes, Durst, Matthias, Dworniczak, Bernd, Eccles, Diana, Edwards, Todd, Eeles, Ros, Eilber, Ursula, Ejlertsen, Bent, Ekici, Arif B., Ellis, Steve, Elvira, Mingajeva, Eng, Kevin H., Engel, Christoph, Evans, D. Gareth, Fasching, Peter A., Ferguson, Sarah, Ferrer, Sandra Fert, Flanagan, James M., Fogarty, Zachary C., Fortner, Renee T., Fostira, Florentia, Foulkes, William D., Fountzilas, George, Fridley, Brooke L., Friebel, Tara M., Friedman, Eitan, Frost, Debra, Ganz, Patricia A., Garber, Judy, Garcia, Maria J., Garcia-Barberan, Vanesa, Gehrig, Andrea, Gentry-Maharaj, Aleksandra, Gerdes, Anne-Marie, Giles, Graham G., Glasspool, Rosalind, Glendon, Gord, Godwin, Andrew K., Goldgar, David E., Goranova, Teodora, Gore, Martin, Greene, Mark H., Gronwald, Jacek, Gruber, Stephen, Hahnen, Eric, Haiman, Christopher A., Hakansson, Niclas, Hamann, Ute, Hansen, Thomas V. O., Harrington, Patricia A., Harris, Holly R., Hauke, Jan, Hein, Alexander, Henderson, Alex, Hildebrandt, Michelle A. T., Hillemanns, Peter, Hodgson, Shirley, Hogdall, Claus K., Hogdall, Estrid, Hogervorst, Frans B. L., Holland, Helene, Hooning, Maartje J., Hosking, Karen, Huang, Ruea-Yea, Hulick, Peter J., Hung, Jillian, Hunter, David J., Huntsman, David G., Huzarski, Tomasz, Imyanitov, Evgeny N., Isaacs, Claudine, Iversen, Edwin S., Izatt, Louise, Izquierdo, Angel, Jakubowska, Anna, James, Paul, Janavicius, Ramunas, Jernetz, Mats, Jensen, Allan, Jensen, Uffe Birk, John, Esther M., Johnatty, Sharon, Jones, Michael E., Kannisto, Paivi, Karlan, Beth Y., Karnezis, Anthony, Kast, Karin, Kennedy, Catherine J., Khusnutdinova, Elza, Kiemeney, Lambertus A., Kiiski, Johanna I., Kim, Sung-Won, Kjaer, Susanne K., Kobel, Martin, Kopperud, Reidun K., Kruse, Torben A., Kupryjanczyk, Jolanta, Kwong, Ava, Laitman, Yael, Lambrechts, Diether, Larranaga, Nerea, Larson, Melissa C., Lazaro, Conxi, Le, Nhu D., Le Marchand, Loic, Lee, Jong Won, Lele, Shashikant B., Leminen, Arto, Leroux, Dominique, Lester, Jenny, Lesueur, Fabienne, Levine, Douglas A., Liang, Dong, Liebrich, Clemens, Lilyquist, Jenna, Lipworth, Loren, Lissowska, Jolanta, Lu, Karen H., Lubinski, Jan, Luccarini, Craig, Lundvall, Lene, Mai, Phuong L., Mendoza-Fandino, Gustavo, Manoukian, Siranoush, Massuger, Leon F. A. G., May, Taymaa, Mazoyer, Sylvie, McAlpine, Jessica N., McGuire, Valerie, McLaughlin, John R., McNeish, Iain, Meijers-Heijboer, Hanne, Meindl, Alfons, Menon, Usha, Mensenkamp, Arjen R., Merritt, Melissa A., Milne, Roger L., Mitchell, Gillian, Modugno, Francesmary, Moes-Sosnowska, Joanna, Moffitt, Melissa, Montagna, Marco, Moysich, Kirsten B., Mulligan, Anna Marie, Musinsky, Jacob, Nathanson, Katherine L., Nedergaard, Lotte, Ness, Roberta B., Neuhausen, Susan L., Nevanlinna, Heli, Niederacher, Dieter, Nussbaum, Robert L., Odunsi, Kunle, Olah, Edith, Olopade, Olufunmilayo I., Olsson, Hakan, Olswold, Curtis, O'Malley, David M., Ong, Kai-ren, Onland-Moret, N. Charlotte, Orr, Nicholas, Orsulic, Sandra, Osorio, Ana, Palli, Domenico, Papi, Laura, Park-Simon, Tjoung-Won, Paul, James, Pearce, Celeste L., Pedersen, Inge Sokilde, Peeters, Petra H. M., Peissel, Bernard, Peixoto, Ana, Pejovic, Tanja, Pelttari, Liisa M., Permuth, Jennifer B., Peterlongo, Paolo, Pezzani, Lidia, Pfeiler, Georg, Phillips, Kelly-Anne, Piedmonte, Marion, Pike, Malcolm C., Piskorz, Anna M., Poblete, Samantha R., Pocza, Timea, Poole, Elizabeth M., Poppe, Bruce, Porteous, Mary E., Prieur, Fabienne, Prokofyeva, Darya, Pugh, Elizabeth, Pujana, Miquel Angel, Pujol, Pascal, Radice, Paolo, Rantala, Johanna, Rappaport-Fuerhauser, Christine, Rennert, Gad, Rhiem, Kerstin, Rice, Patricia, Richardson, Andrea, Robson, Mark, Rodriguez, Gustavo C., Rodriguez-Antona, Cristina, Romm, Jane, Rookus, Matti A., Rossing, Mary Anne, Rothstein, Joseph H., Rudolph, Anja, Runnebaum, Ingo B., Salvesen, Helga B., Sandler, Dale P., Schoemaker, Minouk J., Senter, Leigha, Setiawan, V. Wendy, Severi, Gianluca, Sharma, Priyanka, Shelford, Tameka, Siddiqui, Nadeem, Side, Lucy E., Sieh, Weiva, Singer, Christian F., Sobol, Hagay, Song, Honglin, Southey, Melissa C., Spurdle, Amanda B., Stadler, Zsofia, Steinemann, Doris, Stoppa-Lyonnet, Dominique, Sucheston-Campbell, Lara E., Sukiennicki, Grzegorz, Sutphen, Rebecca, Sutter, Christian, Swerdlow, Anthony J., Szabo, Csilla I., Szafron, Lukasz, Tan, Yen Y., Taylor, Jack A., Tea, Muy-Kheng, Teixeira, Manuel R., Teo, Soo-Hwang, Terry, Kathryn L., Thompson, Pamela J., Thomsen, Liv Cecilie Vestrheim, Thull, Darcy L., Tihomirova, Laima, Tinker, Anna V., Tischkowitz, Marc, Tognazzo, Silvia, Toland, Amanda Ewart, Tone, Alicia, Trabert, Britton, Travis, Ruth C., Trichopoulou, Antonia, Tung, Nadine, Tworoger, Shelley S., Van Altena, Anne M., Van den Berg, David, van der Hout, Annemarie H., van der Luijt, Rob B., Van Heetvelde, Mattias, Van Nieuwenhuysen, Els, Van Rensburg, Elizabeth J., Vanderstichele, Adriaan, Varon-Mateeva, Raymonda, Vega, Ana, Edwards, Digna Velez, Vergote, Ignace, Vierkant, Robert A., Vijai, Joseph, Vratimos, Athanassios, Walker, Lisa, Walsh, Christine, Wand, Dorothea, Wang-Gohrke, Shan, Wappenschmidt, Barbara, Webb, Penelope M., Weinberg, Clarice R., Weitzel, Jeffrey N., Wentzensen, Nicolas, Whittemore, Alice S., Wijnen, Juul T., Wilkens, Lynne R., Wolk, Alicja, Woo, Michelle, Wu, Xifeng, Wu, Anna H., Yang, Hannah, Yannoukakos, Drakoulis, Ziogas, Argyrios, Zorn, Kristin K., Narod, Steven A., Easton, Douglas F., Amos, Christopher I., Schildkraut, Joellen M., Ramus, Susan J., Ottini, Laura, Goodman, Marc T., Park-, Sue K., Kelemen, Linda E., Risch, Harvey A., Thomassen, Mads, Offit, Kenneth, Simard, Jacques, Schmutzler, Rita Katharina, Hazelett, Dennis, Monteiro, Alvaro N., Couch, Fergus J., Berchuck, Andrew, Chenevix-Trench, Georgia, Goode, Ellen L., Sellers, Thomas A., Gayther, Simon A., Antoniou, Antonis C., Pharoah, Paul D. P., Phelan, Catherine M., Kuchenbaecker, Karoline B., Tyrer, Jonathan P., Kar, Siddhartha P., Lawrenson, Kate, Winham, Stacey J., Dennis, Joe, Pirie, Ailith, Riggan, Marjorie J., Chornokur, Ganna, Earp, Madalene A., Lyra, Paulo C., Jr., Lee, Janet M., Coetzee, Simon, Beesley, Jonathan, McGuffog, Lesley, Soucy, Penny, Dicks, Ed, Lee, Andrew, Barrowdale, Daniel, Lecarpentier, Julie, Leslie, Goska, Aalfs, Cora M., Aben, Katja K. H., Adams, Marcia, Adlard, Julian, Andrulis, Irene L., Anton-Culver, Hoda, Antonenkova, Natalia, Aravantinos, Gerasimos, Arnold, Norbert, Arun, Banu K., Arver, Brita, Azzollini, Jacopo, Balmana, Judith, Banerjee, Susana N., Barjhoux, Laure, Barkardottir, Rosa B., Bean, Yukie, Beckmann, Matthias W., Beeghly-Fadiel, Alicia, Benitez, Javier, Bermisheva, Marina, Bernardini, Marcus Q., Birrer, Michael J., Bjorge, Line, Black, Amanda, Blankstein, Kenneth, Blok, Marinus J., Bodelon, Clara, Bogdanova, Natalia, Bojesen, Anders, Bonanni, Bernardo, Borg, Ake, Bradbury, Angela R., Brenton, James D., Brewer, Carole, Brinton, Louise, Broberg, Per, Brooks-Wilson, Angela, Bruinsma, Fiona, Brunet, Joan, Buecher, Bruno, Butzow, Ralf, Buys, Saundra S., Caldes, Trinidad, Caligo, Maria A., Campbell, Ian, Cannioto, Rikki, Carney, Michael E., Cescon, Terence, Chan, Salina B., Chang-Claude, Jenny, Chanock, Stephen, Chen, Xiao Qing, Chiew, Yoke-Eng, Chiquette, Jocelyne, Chung, Wendy K., Claes, Kathleen B. M., Conner, Thomas, Cook, Linda S., Cook, Jackie, Cramer, Daniel W., Cunningham, Julie M., D'Aloisio, Aimee A., Daly, Mary B., Damiola, Francesca, Damirovna, Sakaeva Dina, Dansonka-Mieszkowska, Agnieszka, Dao, Fanny, Davidson, Rosemarie, DeFazio, Anna, Delnatte, Capucine, Doheny, Kimberly F., Diez, Orland, Ding, Yuan Chun, Doherty, Jennifer Anne, Domchek, Susan M., Dorfling, Cecilia M., Dork, Thilo, Dossus, Laure, Duran, Mercedes, Durst, Matthias, Dworniczak, Bernd, Eccles, Diana, Edwards, Todd, Eeles, Ros, Eilber, Ursula, Ejlertsen, Bent, Ekici, Arif B., Ellis, Steve, Elvira, Mingajeva, Eng, Kevin H., Engel, Christoph, Evans, D. Gareth, Fasching, Peter A., Ferguson, Sarah, Ferrer, Sandra Fert, Flanagan, James M., Fogarty, Zachary C., Fortner, Renee T., Fostira, Florentia, Foulkes, William D., Fountzilas, George, Fridley, Brooke L., Friebel, Tara M., Friedman, Eitan, Frost, Debra, Ganz, Patricia A., Garber, Judy, Garcia, Maria J., Garcia-Barberan, Vanesa, Gehrig, Andrea, Gentry-Maharaj, Aleksandra, Gerdes, Anne-Marie, Giles, Graham G., Glasspool, Rosalind, Glendon, Gord, Godwin, Andrew K., Goldgar, David E., Goranova, Teodora, Gore, Martin, Greene, Mark H., Gronwald, Jacek, Gruber, Stephen, Hahnen, Eric, Haiman, Christopher A., Hakansson, Niclas, Hamann, Ute, Hansen, Thomas V. O., Harrington, Patricia A., Harris, Holly R., Hauke, Jan, Hein, Alexander, Henderson, Alex, Hildebrandt, Michelle A. T., Hillemanns, Peter, Hodgson, Shirley, Hogdall, Claus K., Hogdall, Estrid, Hogervorst, Frans B. L., Holland, Helene, Hooning, Maartje J., Hosking, Karen, Huang, Ruea-Yea, Hulick, Peter J., Hung, Jillian, Hunter, David J., Huntsman, David G., Huzarski, Tomasz, Imyanitov, Evgeny N., Isaacs, Claudine, Iversen, Edwin S., Izatt, Louise, Izquierdo, Angel, Jakubowska, Anna, James, Paul, Janavicius, Ramunas, Jernetz, Mats, Jensen, Allan, Jensen, Uffe Birk, John, Esther M., Johnatty, Sharon, Jones, Michael E., Kannisto, Paivi, Karlan, Beth Y., Karnezis, Anthony, Kast, Karin, Kennedy, Catherine J., Khusnutdinova, Elza, Kiemeney, Lambertus A., Kiiski, Johanna I., Kim, Sung-Won, Kjaer, Susanne K., Kobel, Martin, Kopperud, Reidun K., Kruse, Torben A., Kupryjanczyk, Jolanta, Kwong, Ava, Laitman, Yael, Lambrechts, Diether, Larranaga, Nerea, Larson, Melissa C., Lazaro, Conxi, Le, Nhu D., Le Marchand, Loic, Lee, Jong Won, Lele, Shashikant B., Leminen, Arto, Leroux, Dominique, Lester, Jenny, Lesueur, Fabienne, Levine, Douglas A., Liang, Dong, Liebrich, Clemens, Lilyquist, Jenna, Lipworth, Loren, Lissowska, Jolanta, Lu, Karen H., Lubinski, Jan, Luccarini, Craig, Lundvall, Lene, Mai, Phuong L., Mendoza-Fandino, Gustavo, Manoukian, Siranoush, Massuger, Leon F. A. G., May, Taymaa, Mazoyer, Sylvie, McAlpine, Jessica N., McGuire, Valerie, McLaughlin, John R., McNeish, Iain, Meijers-Heijboer, Hanne, Meindl, Alfons, Menon, Usha, Mensenkamp, Arjen R., Merritt, Melissa A., Milne, Roger L., Mitchell, Gillian, Modugno, Francesmary, Moes-Sosnowska, Joanna, Moffitt, Melissa, Montagna, Marco, Moysich, Kirsten B., Mulligan, Anna Marie, Musinsky, Jacob, Nathanson, Katherine L., Nedergaard, Lotte, Ness, Roberta B., Neuhausen, Susan L., Nevanlinna, Heli, Niederacher, Dieter, Nussbaum, Robert L., Odunsi, Kunle, Olah, Edith, Olopade, Olufunmilayo I., Olsson, Hakan, Olswold, Curtis, O'Malley, David M., Ong, Kai-ren, Onland-Moret, N. Charlotte, Orr, Nicholas, Orsulic, Sandra, Osorio, Ana, Palli, Domenico, Papi, Laura, Park-Simon, Tjoung-Won, Paul, James, Pearce, Celeste L., Pedersen, Inge Sokilde, Peeters, Petra H. M., Peissel, Bernard, Peixoto, Ana, Pejovic, Tanja, Pelttari, Liisa M., Permuth, Jennifer B., Peterlongo, Paolo, Pezzani, Lidia, Pfeiler, Georg, Phillips, Kelly-Anne, Piedmonte, Marion, Pike, Malcolm C., Piskorz, Anna M., Poblete, Samantha R., Pocza, Timea, Poole, Elizabeth M., Poppe, Bruce, Porteous, Mary E., Prieur, Fabienne, Prokofyeva, Darya, Pugh, Elizabeth, Pujana, Miquel Angel, Pujol, Pascal, Radice, Paolo, Rantala, Johanna, Rappaport-Fuerhauser, Christine, Rennert, Gad, Rhiem, Kerstin, Rice, Patricia, Richardson, Andrea, Robson, Mark, Rodriguez, Gustavo C., Rodriguez-Antona, Cristina, Romm, Jane, Rookus, Matti A., Rossing, Mary Anne, Rothstein, Joseph H., Rudolph, Anja, Runnebaum, Ingo B., Salvesen, Helga B., Sandler, Dale P., Schoemaker, Minouk J., Senter, Leigha, Setiawan, V. Wendy, Severi, Gianluca, Sharma, Priyanka, Shelford, Tameka, Siddiqui, Nadeem, Side, Lucy E., Sieh, Weiva, Singer, Christian F., Sobol, Hagay, Song, Honglin, Southey, Melissa C., Spurdle, Amanda B., Stadler, Zsofia, Steinemann, Doris, Stoppa-Lyonnet, Dominique, Sucheston-Campbell, Lara E., Sukiennicki, Grzegorz, Sutphen, Rebecca, Sutter, Christian, Swerdlow, Anthony J., Szabo, Csilla I., Szafron, Lukasz, Tan, Yen Y., Taylor, Jack A., Tea, Muy-Kheng, Teixeira, Manuel R., Teo, Soo-Hwang, Terry, Kathryn L., Thompson, Pamela J., Thomsen, Liv Cecilie Vestrheim, Thull, Darcy L., Tihomirova, Laima, Tinker, Anna V., Tischkowitz, Marc, Tognazzo, Silvia, Toland, Amanda Ewart, Tone, Alicia, Trabert, Britton, Travis, Ruth C., Trichopoulou, Antonia, Tung, Nadine, Tworoger, Shelley S., Van Altena, Anne M., Van den Berg, David, van der Hout, Annemarie H., van der Luijt, Rob B., Van Heetvelde, Mattias, Van Nieuwenhuysen, Els, Van Rensburg, Elizabeth J., Vanderstichele, Adriaan, Varon-Mateeva, Raymonda, Vega, Ana, Edwards, Digna Velez, Vergote, Ignace, Vierkant, Robert A., Vijai, Joseph, Vratimos, Athanassios, Walker, Lisa, Walsh, Christine, Wand, Dorothea, Wang-Gohrke, Shan, Wappenschmidt, Barbara, Webb, Penelope M., Weinberg, Clarice R., Weitzel, Jeffrey N., Wentzensen, Nicolas, Whittemore, Alice S., Wijnen, Juul T., Wilkens, Lynne R., Wolk, Alicja, Woo, Michelle, Wu, Xifeng, Wu, Anna H., Yang, Hannah, Yannoukakos, Drakoulis, Ziogas, Argyrios, Zorn, Kristin K., Narod, Steven A., Easton, Douglas F., Amos, Christopher I., Schildkraut, Joellen M., Ramus, Susan J., Ottini, Laura, Goodman, Marc T., Park-, Sue K., Kelemen, Linda E., Risch, Harvey A., Thomassen, Mads, Offit, Kenneth, Simard, Jacques, Schmutzler, Rita Katharina, Hazelett, Dennis, Monteiro, Alvaro N., Couch, Fergus J., Berchuck, Andrew, Chenevix-Trench, Georgia, Goode, Ellen L., Sellers, Thomas A., Gayther, Simon A., Antoniou, Antonis C., and Pharoah, Paul D. P.
Abstract: To identify common alleles associated with different histotypes of epithelial ovarian cancer (EOC), we pooled data from multiple genome-wide genotyping projects totaling 25,509 EOC cases and 40,941 controls. We identified nine new susceptibility loci for different EOC histotypes: six for serous EOC histotypes (3q28, 4q32.3, 8q21.11, 10q24.33, 18q11.2 and 22q12.1), two for mucinous EOC (3q22.3 and 9q31.1) and one for endometrioid EOC (5q12.3). We then performed meta-analysis on the results for high-grade serous ovarian cancer with the results from analysis of 31,448 BRCA1 and BRCA2 mutation carriers, including 3,887 mutation carriers with EOC. This identified three additional susceptibility loci at 2q13, 8q24.1 and 12q24.31. Integrated analyses of genes and regulatory biofeatures at each locus predicted candidate susceptibility genes, including OBFC1, a new candidate susceptibility gene for low-grade and borderline serous EOC.
Published: 2017

40. Consensus Recommendation of the German Consortium Family Breast and Ovarian Cancer for dealing with Results of the Multigenic Analysis

Author: Waha, Anke, Versmold, Beatrix, Kast, Karin, Kiechle, Marion, Ditsch, Nina, Meindl, Alfons, Niederacher, Dieter, Hahnen, Eric, Arnold, Norbert, Mundhenke, Christoph, Horvath, Judit, Auber, Bernd, Dikow, Nicola, Hauke, Jan, Wappenschmidt, Barbara, Riess, Olaf, Schott, Sarah, Speiser, Dorothee, Faust, Ulrike, Sutter, Christian, Rhiem, Kerstin, Schmutzler, Rita Katharina, Waha, Anke, Versmold, Beatrix, Kast, Karin, Kiechle, Marion, Ditsch, Nina, Meindl, Alfons, Niederacher, Dieter, Hahnen, Eric, Arnold, Norbert, Mundhenke, Christoph, Horvath, Judit, Auber, Bernd, Dikow, Nicola, Hauke, Jan, Wappenschmidt, Barbara, Riess, Olaf, Schott, Sarah, Speiser, Dorothee, Faust, Ulrike, Sutter, Christian, Rhiem, Kerstin, and Schmutzler, Rita Katharina
Published: 2017

41. Use of the BOADICEA breast cancer risk prediction tool in clinical practice: appraisals across clinicians from various countries.

Author: Bredart, Anne, Kop, Jean-Luc, Antoniou, Antonis, De Pauw, Antoine, Tischkowitz, Marc, Ehrencrona, Hans, Dolbeault, Sylvie, Robieux, Leonore, Stoppa-Lyonnet, Dominique, Schmutzler, Rita Katharina, Bredart, Anne, Kop, Jean-Luc, Antoniou, Antonis, De Pauw, Antoine, Tischkowitz, Marc, Ehrencrona, Hans, Dolbeault, Sylvie, Robieux, Leonore, Stoppa-Lyonnet, Dominique, and Schmutzler, Rita Katharina
Published: 2017

42. Prevalence of deleterious germline variants in risk genes including BRCA1/2 in consecutive ovarian cancer patients (AGO-TR-1)

Author: Galli, Alvaro, Harter, Philipp, Hauke, Jan, Heitz, Florian, Reuss, Alexander, Kommoss, Stefan, Marmé, Frederik, Heimbach, André, Prieske, Katharina, Richters, Lisa, Burges, Alexander, Neidhardt, Guido, Gregorio, Nikolaus de, Balat, Ahmed el, Hilpert, Felix, Meier, Werner, Kimmig, Rainer, Kast, Karin, Sehouli, Jalid, Baumann, Klaus, Jackisch, Christian, Park-Simon, Tjoung-Won, Hanker, Lars, Kröber, Sandra, Pfisterer, Jacobus, Gevensleben, Heidrun, Schnelzer, Andreas, Dietrich, Dimo, Neunhöffer, Tanja, Krockenberger, Mathias Heinric, Brucker, Sara, Nürnberg, Peter, Thiele, Holger, Altmüller, Janine, Lamla, Josefin, Elser, Gabriele, Du Bois, Andreas, Hahnen, Eric Thomas, Schmutzler, Rita Katharina, Galli, Alvaro, Harter, Philipp, Hauke, Jan, Heitz, Florian, Reuss, Alexander, Kommoss, Stefan, Marmé, Frederik, Heimbach, André, Prieske, Katharina, Richters, Lisa, Burges, Alexander, Neidhardt, Guido, Gregorio, Nikolaus de, Balat, Ahmed el, Hilpert, Felix, Meier, Werner, Kimmig, Rainer, Kast, Karin, Sehouli, Jalid, Baumann, Klaus, Jackisch, Christian, Park-Simon, Tjoung-Won, Hanker, Lars, Kröber, Sandra, Pfisterer, Jacobus, Gevensleben, Heidrun, Schnelzer, Andreas, Dietrich, Dimo, Neunhöffer, Tanja, Krockenberger, Mathias Heinric, Brucker, Sara, Nürnberg, Peter, Thiele, Holger, Altmüller, Janine, Lamla, Josefin, Elser, Gabriele, Du Bois, Andreas, Hahnen, Eric Thomas, and Schmutzler, Rita Katharina
Abstract: Background: Identification of families at risk for ovarian cancer offers the opportunity to consider prophylactic surgery thus reducing ovarian cancer mortality. So far, identification of potentially affected families in Germany was solely performed via family history and numbers of affected family members with breast or ovarian cancer. However, neither the prevalence of deleterious variants in BRCA1/2 in ovarian cancer in Germany nor the reliability of family history as trigger for genetic counselling has ever been evaluated. Methods: Prospective counseling and germline testing of consecutive patients with primary diagnosis or with platinum-sensitive relapse of an invasive epithelial ovarian cancer. Testing included 25 candidate and established risk genes. Among these 25 genes, 16 genes (ATM, BRCA1, BRCA2, CDH1, CHEK2, MLH1, MSH2, MSH6, NBN, PMS2, PTEN, PALB2, RAD51C, RAD51D, STK11, TP53) were defined as established cancer risk genes. A positive family history was defined as at least one relative with breast cancer or ovarian cancer or breast cancer in personal history. Results: In total, we analyzed 523 patients: 281 patients with primary diagnosis of ovarian cancer and 242 patients with relapsed disease. Median age at primary diagnosis was 58 years (range 16–93) and 406 patients (77.6%) had a high-grade serous ovarian cancer. In total, 27.9% of the patients showed at least one deleterious variant in all 25 investigated genes and 26.4% in the defined 16 risk genes. Deleterious variants were most prevalent in the BRCA1 (15.5%), BRCA2 (5.5%), RAD51C (2.5%) and PALB2 (1.1%) genes. The prevalence of deleterious variants did not differ significantly between patients at primary diagnosis and relapse. The prevalence of deleterious variants in BRCA1/2 (and in all 16 risk genes) in patients <60 years was 30.2% (33.2%) versus 10.6% (18.9%) in patients ≥60 years. Family history was positive in 43% of all patients. Patients with a positive family history had a prevalence of d
Published: 2017

43. Fine-Scale Mapping at 9p22.2 Identifies Candidate Causal Variants That Modify Ovarian Cancer Risk in BRCA1 and BRCA2 Mutation Carriers

Author: Vigorito, Elena, Kuchenbaecker, Karoline B., Beesley, Jonathan, Adlard, Julian, Agnarsson, Bjarni A., Andrulis, Irene L., Arun, Banu K., Barjhoux, Laure, Belotti, Muriel, Benitez, Javier, Berger, Andreas, Bojesen, Anders, Bonanni, Bernardo, Brewer, Carole, Caldes, Trinidad, Caligo, Maria A., Campbell, Ian, Chan, Salina B., Claes, Kathleen B. M., Cohn, David E., Cook, Jackie, Daly, Mary B., Damiola, Francesca, Davidson, Rosemarie, de Pauw, Antoine, Delnatte, Capucine, Diez, Orland, Domchek, Susan M., Dumont, Martine, Durda, Katarzyna, Dworniczak, Bernd, Easton, Douglas F., Eccles, Diana, Edwinsdotter Ardnor, Christina, Eeles, Ros, Ejlertsen, Bent, Ellis, Steve, Evans, D. Gareth, Feliubadalo, Lidia, Fostira, Florentia, Foulkes, William D., Friedman, Eitan, Frost, Debra, Gaddam, Pragna, Ganz, Patricia A., Garber, Judy, Garcia-Barberan, Vanesa, Gauthier-Villars, Marion, Gehrig, Andrea, Gerdes, Anne-Marie, Giraud, Sophie, Godwin, Andrew K., Goldgar, David E., Hake, Christopher R., Hansen, Thomas V. O., Healey, Sue, Hodgson, Shirley, Hogervorst, Frans B. L., Houdayer, Claude, Hulick, Peter J., Imyanitov, Evgeny N., Isaacs, Claudine, Izatt, Louise, Izquierdo, Angel, Jacobs, Lauren, Jakubowska, Anna, Janavicius, Ramunas, Jaworska-Bieniek, Katarzyna, Jensen, Uffe Birk, John, Esther M., Vijai, Joseph, Karlan, Beth Y., Kast, Karin, Khan, Sofia, Kwong, Ava, Laitman, Yael, Lester, Jenny, Lesueur, Fabienne, Liljegren, Annelie, Lubinski, Jan, Mai, Phuong L., Manoukian, Siranoush, Mazoyer, Sylvie, Meindl, Alfons, Mensenkamp, Arjen R., Montagna, Marco, Nathanson, Katherine L., Neuhausen, Susan L., Nevanlinna, Heli, Niederacher, Dieter, Olah, Edith, Olopade, Olufunmilayo I., Ong, Kai-ren, Osorio, Ana, Park, Sue Kyung, Paulsson-Karlsson, Ylva, Pedersen, Inge Sokilde, Peissel, Bernard, Peterlongo, Paolo, Pfeiler, Georg, Phelan, Catherine M., Piedmonte, Marion, Poppe, Bruce, Angel Pujana, Miquel, Radice, Paolo, Rennert, Gad, Rodriguez, Gustavo C., Rookus, Matti A., Ross, Eric A., Schmutzler, Rita Katharina, Simard, Jacques, Singer, Christian F., Slavin, Thomas P., Soucy, Penny, Southey, Melissa, Steinemann, Doris, Stoppa-Lyonnet, Dominique, Sukiennicki, Grzegorz, Sutter, Christian, Szabo, Csilla I., Tea, Muy-Kheng, Teixeira, Manuel R., Teo, Soo-Hwang, Terry, Mary Beth, Thomassen, Mads, Tibiletti, Maria Grazia, Tihomirova, Laima, Tognazzo, Silvia, van Rensburg, Elizabeth J., Varesco, Liliana, Varon-Mateeva, Raymonda, Vratimos, Athanassios, Weitzel, Jeffrey N., McGuffog, Lesley, Kirk, Judy, Toland, Amanda Ewart, Hamann, Ute, Lindor, Noralane, Ramus, Susan J., Greene, Mark H., Couch, Fergus J., Offit, Kenneth, Pharoah, Paul D. P., Chenevix-Trench, Georgia, and Antoniou, Antonis C.
Subjects: Heredity, endocrine system diseases, Genes, BRCA2, Genes, BRCA1, Mathematical and Statistical Techniques, Basic Cancer Research, Medicine and Health Sciences, INVESTIGATORS, skin and connective tissue diseases, Ovarian Neoplasms, Genetic Carrier Screening, Chromosome Mapping, Genomics, Ovarian Cancer, Genetic Mapping, Oncology, Physical Sciences, Female, Chromosomes, Human, Pair 9, Medical Genetics, Statistics (Mathematics), Research Article, SUSCEPTIBILITY LOCI, CENTLEIN, Variant Genotypes, Research and Analysis Methods, Polymorphism, Single Nucleotide, BREAST, Cancer Genomics, Genomic Medicine, Diagnostic Medicine, Genetics, Genome-Wide Association Studies, Cancer Detection and Diagnosis, Humans, Genetic Predisposition to Disease, ddc:610, Statistical Methods, GENOME-WIDE ASSOCIATION, Alleles, Medicinsk genetik, Cancer och onkologi, CONSORTIUM, Cancers and Neoplasms, Computational Biology, Biology and Life Sciences, Human Genetics, Genome Analysis, PATHOLOGY, Genetic Loci, Cancer and Oncology, Mutation, Gynecological Tumors, Mathematics, Meta-Analysis
Abstract: Population-based genome wide association studies have identified a locus at 9p22.2 associated with ovarian cancer risk, which also modifies ovarian cancer risk in BRCA1 and BRCA2 mutation carriers. We conducted fine-scale mapping at 9p22.2 to identify potential causal variants in BRCA1 and BRCA2 mutation carriers. Genotype data were available for 15,252 (2,462 ovarian cancer cases) BRCA1 and 8,211 (631 ovarian cancer cases) BRCA2 mutation carriers. Following genotype imputation, ovarian cancer associations were assessed for 4,873 and 5,020 SNPs in BRCA1 and BRCA2 mutation carriers respectively, within a retrospective cohort analytical framework. In BRCA1 mutation carriers one set of eight correlated candidate causal variants for ovarian cancer risk modification was identified (top SNP rs10124837, HR: 0.73, 95% CI: 0.68 to 0.79, p-value 2x 10-16). These variants were located up to 20 kb upstream of BNC2. In BRCA2 mutation carriers one region, up to 45 kb upstream of BNC2, and containing 100 correlated SNPs was identified as candidate causal (top SNP rs62543585, HR: 0.69, 95% CI: 0.59 to 0.80, p-value 1.0 x 10-6). The candidate causal in BRCA1 mutation carriers did not include the strongest associated variant at this locus in the general population. In sum, we identified a set of candidate causal variants in a region that encompasses the BNC2 transcription start site. The ovarian cancer association at 9p22.2 may be mediated by different variants in BRCA1 mutation carriers and in the general population. Thus, potentially different mechanisms may underlie ovarian cancer risk for mutation carriers and the general population.
Published: 2016

44. Identification of six new susceptibility loci for invasive epithelial ovarian cancer

Author: Kuchenbaecker, Karoline B., Ramus, Susan J., Tyrer, Jonathan, Lee, Andrew, Shen, Howard C., Beesley, Jonathan, Lawrenson, Kate, McGuffog, Lesley, Healey, Sue, Lee, Janet M., Spindler, Tassja J., Lin, Yvonne G., Pejovic, Tanja, Bean, Yukie, Li, Qiyuan, Coetzee, Simon, Hazelett, Dennis, Miron, Alexander, Southey, Melissa, Terry, Mary Beth, Goldgar, David E., Buys, Saundra S., Janavicius, Ramunas, Dorfling, Cecilia M., van Rensburg, Elizabeth J., Neuhausen, Susan L., Ding, Yuan Chun, Hansen, Thomas V. O., Jonson, Lars, Gerdes, Anne-Marie, Ejlertsen, Bent, Barrowdale, Daniel, Dennis, Joe, Benitez, Javier, Osorio, Ana, Garcia, Maria Jose, Komenaka, Ian, Weitzel, Jeffrey N., Ganschow, Pamela, Peterlongo, Paolo, Bernard, Loris, Viel, Alessandra, Bonanni, Bernardo, Peissel, Bernard, Manoukian, Siranoush, Radice, Paolo, Papi, Laura, Ottini, Laura, Fostira, Florentia, Konstantopoulou, Irene, Garber, Judy, Frost, Debra, Perkins, Jo, Platte, Radka, Ellis, Steve, Godwin, Andrew K., Schmutzler, Rita Katharina, Meindl, Alfons, Engel, Christoph, Sutter, Christian, Sinilnikova, Olga M., Damiola, Francesca, Mazoyer, Sylvie, Stoppa-Lyonnet, Dominique, Claes, Kathleen, De Leeneer, Kim, Kirk, Judy, Rodriguez, Gustavo C., Piedmonte, Marion, O'Malley, David M., de la Hoya, Miguel, Caldes, Trinidad, Aittomaeki, Kristiina, Nevanlinna, Heli, Collee, J. Margriet, Rookus, Matti A., Oosterwijk, Jan C., Tihomirova, Laima, Tung, Nadine, Hamann, Ute, Isaccs, Claudine, Tischkowitz, Marc, Imyanitov, Evgeny N., Caligo, Maria A., Campbell, Ian G., Hogervorst, Frans B. L., Olah, Edith, Diez, Orland, Blanco, Ignacio, Brunet, Joan, Lazaroso, Conxi, Angel Pujana, Miguel, Jakubowska, Anna, Gronwald, Jacek, Lubinski, Jan, Sukiennicki, Grzegorz, Barkardottir, Rosa B., Plante, Marie, Simard, Jacques, Soucy, Penny, Montagna, Marco, Tognazzo, Silvia, Teixeira, Manuel R., Pankratz, Vernon S., Wang, Xianshu, Lindor, Noralane, Szabo, Csilla I., Kauff, Noah, Vijai, Joseph, Aghajanian, Carol A., Pfeiler, Georg, Berger, Andreas, Singer, Christian F., Tea, Muy-Kheng, Phelan, Catherine M., Greene, Mark H., Mai, Phuong L., Rennert, Gad, Mulligan, Anna Marie, Tchatchou, Sandrine, Andrulis, Irene L., Glendon, Gord, Toland, Amanda Ewart, Jensen, Uffe Birk, Kruse, Torben A., Thomassen, Mads, Bojesen, Anders, Zidan, Jamal, Friedman, Eitan, Laitman, Yael, Soller, Maria, Liljegren, Annelie, Arver, Brita, Einbeigi, Zakaria, Stenmark-Askmalm, Marie, Olopade, Olufunmilayo I., Nussbaum, Robert L., Rebbeck, Timothy R., Nathanson, Katherine L., Domchek, Susan M., Lu, Karen H., Karlan, Beth Y., Walsh, Christine, Lester, Jenny, Hein, Alexander, Ekici, Arif B., Beckmann, Matthias W., Fasching, Peter A., Lambrechts, Diether, Van Nieuwenhuysen, Els, Vergote, Ignace, Lambrechts, Sandrina, Dicks, Ed, Doherty, Jennifer A., Wicklund, Kristine G., Rossing, Mary Anne, Rudolph, Anja, Chang-Claude, Jenny, Wang-Gohrke, Shan, Eilber, Ursula, Moysich, Kirsten B., Odunsi, Kunle, Sucheston, Lara, Lele, Shashi, Wilkens, Lynne R., Goodman, Marc T., Thompson, Pamela J., Shvetsov, Yurii B., Runnebaum, Ingo B., Duerst, Matthias, Hillemanns, Peter, Doerk, Thilo, Antonenkova, Natalia, Bogdanova, Natalia, Leminen, Arto, Pelttari, Liisa M., Butzow, Ralf, Modugno, Francesmary, Kelley, Joseph L., Edwards, Robert P., Ness, Roberta B., du Bois, Andreas, Heitz, Florian, Schwaab, Ira, Harter, Philipp, Matsuo, Keitaro, Hosono, Satoyo, Orsulic, Sandra, Jensen, Allan, Kjaer, Susanne Kruger, Hogdall, Estrid, Hasmad, Hanis Nazihah, Azmi, Mat Adenan Noor, Teo, Soo-Hwang, Woo, Yin-Ling, Fridley, Brooke L., Goode, Ellen L., Cunningham, Julie M., Vierkant, Robert A., Bruinsma, Fiona, Giles, Graham G., Liang, Dong, Hildebrandt, Michelle A. T., Wu, Xifeng, Levine, Douglas A., Bisogna, Maria, Berchuck, Andrew, Iversen, Edwin S., Schildkraut, Joellen M., Concannon, Patrick, Weber, Rachel Palmieri, Cramer, Daniel W., Terry, Kathryn L., Poole, Elizabeth M., Tworoger, Shelley S., Bandera, Elisa V., Orlow, Irene, Olson, Sara H., Krakstad, Camilla, Salvesen, Helga B., Tangen, Ingvild L., Bjorge, Line, van Altena, Anne M., Aben, Katja K. H., Kiemeney, Lambertus A., Massuger, Leon F. A. G., Kellar, Melissa, Brooks-Wilson, Angela, Kelemen, Linda E., Cook, Linda S., Le, Nhu D., Cybulski, Cezary, Yang, Hannah, Lissowska, Jolanta, Brinton, Louise A., Wentzensen, Nicolas, Hogdall, Claus, Lundvall, Lene, Nedergaard, Lotte, Baker, Helen, Song, Honglin, Eccles, Diana, McNeish, Ian, Paul, James, Carty, Karen, Siddiqui, Nadeem, Glasspool, Rosalind, Whittemore, Alice S., Rothstein, Joseph H., McGuire, Valerie, Sieh, Weiva, Ji, Bu-Tian, Zheng, Wei, Shu, Xiao-Ou, Gao, Yu-Tang, Rosen, Barry, Risch, Harvey A., McLaughlin, John R., Narod, Steven A., Monteiro, Alvaro N., Chen, Ann, Lin, Hui-Yi, Permuth-Wey, Jenny, Sellers, Thomas A., Tsai, Ya-Yu, Chen, Zhihua, Ziogas, Argyrios, Anton-Culver, Hoda, Gentry-Maharaj, Aleksandra, Menon, Usha, Harrington, Patricia, Lee, Alice W., Wu, Anna H., Pearce, Celeste L., Coetzee, Gerry, Pike, Malcolm C., Dansonka-Mieszkowska, Agnieszka, Timorek, Agnieszka, Rzepecka, Iwona K., Kupryjanczyk, Jolanta, Freedman, Matt, Noushmehr, Houtan, Easton, Douglas F., Offit, Kenneth, Couch, Fergus J., Gayther, Simon, Pharoah, Paul P., Antoniou, Antonis C., Chenevix-Trench, Georgia, Kuchenbaecker, Karoline B., Ramus, Susan J., Tyrer, Jonathan, Lee, Andrew, Shen, Howard C., Beesley, Jonathan, Lawrenson, Kate, McGuffog, Lesley, Healey, Sue, Lee, Janet M., Spindler, Tassja J., Lin, Yvonne G., Pejovic, Tanja, Bean, Yukie, Li, Qiyuan, Coetzee, Simon, Hazelett, Dennis, Miron, Alexander, Southey, Melissa, Terry, Mary Beth, Goldgar, David E., Buys, Saundra S., Janavicius, Ramunas, Dorfling, Cecilia M., van Rensburg, Elizabeth J., Neuhausen, Susan L., Ding, Yuan Chun, Hansen, Thomas V. O., Jonson, Lars, Gerdes, Anne-Marie, Ejlertsen, Bent, Barrowdale, Daniel, Dennis, Joe, Benitez, Javier, Osorio, Ana, Garcia, Maria Jose, Komenaka, Ian, Weitzel, Jeffrey N., Ganschow, Pamela, Peterlongo, Paolo, Bernard, Loris, Viel, Alessandra, Bonanni, Bernardo, Peissel, Bernard, Manoukian, Siranoush, Radice, Paolo, Papi, Laura, Ottini, Laura, Fostira, Florentia, Konstantopoulou, Irene, Garber, Judy, Frost, Debra, Perkins, Jo, Platte, Radka, Ellis, Steve, Godwin, Andrew K., Schmutzler, Rita Katharina, Meindl, Alfons, Engel, Christoph, Sutter, Christian, Sinilnikova, Olga M., Damiola, Francesca, Mazoyer, Sylvie, Stoppa-Lyonnet, Dominique, Claes, Kathleen, De Leeneer, Kim, Kirk, Judy, Rodriguez, Gustavo C., Piedmonte, Marion, O'Malley, David M., de la Hoya, Miguel, Caldes, Trinidad, Aittomaeki, Kristiina, Nevanlinna, Heli, Collee, J. Margriet, Rookus, Matti A., Oosterwijk, Jan C., Tihomirova, Laima, Tung, Nadine, Hamann, Ute, Isaccs, Claudine, Tischkowitz, Marc, Imyanitov, Evgeny N., Caligo, Maria A., Campbell, Ian G., Hogervorst, Frans B. L., Olah, Edith, Diez, Orland, Blanco, Ignacio, Brunet, Joan, Lazaroso, Conxi, Angel Pujana, Miguel, Jakubowska, Anna, Gronwald, Jacek, Lubinski, Jan, Sukiennicki, Grzegorz, Barkardottir, Rosa B., Plante, Marie, Simard, Jacques, Soucy, Penny, Montagna, Marco, Tognazzo, Silvia, Teixeira, Manuel R., Pankratz, Vernon S., Wang, Xianshu, Lindor, Noralane, Szabo, Csilla I., Kauff, Noah, Vijai, Joseph, Aghajanian, Carol A., Pfeiler, Georg, Berger, Andreas, Singer, Christian F., Tea, Muy-Kheng, Phelan, Catherine M., Greene, Mark H., Mai, Phuong L., Rennert, Gad, Mulligan, Anna Marie, Tchatchou, Sandrine, Andrulis, Irene L., Glendon, Gord, Toland, Amanda Ewart, Jensen, Uffe Birk, Kruse, Torben A., Thomassen, Mads, Bojesen, Anders, Zidan, Jamal, Friedman, Eitan, Laitman, Yael, Soller, Maria, Liljegren, Annelie, Arver, Brita, Einbeigi, Zakaria, Stenmark-Askmalm, Marie, Olopade, Olufunmilayo I., Nussbaum, Robert L., Rebbeck, Timothy R., Nathanson, Katherine L., Domchek, Susan M., Lu, Karen H., Karlan, Beth Y., Walsh, Christine, Lester, Jenny, Hein, Alexander, Ekici, Arif B., Beckmann, Matthias W., Fasching, Peter A., Lambrechts, Diether, Van Nieuwenhuysen, Els, Vergote, Ignace, Lambrechts, Sandrina, Dicks, Ed, Doherty, Jennifer A., Wicklund, Kristine G., Rossing, Mary Anne, Rudolph, Anja, Chang-Claude, Jenny, Wang-Gohrke, Shan, Eilber, Ursula, Moysich, Kirsten B., Odunsi, Kunle, Sucheston, Lara, Lele, Shashi, Wilkens, Lynne R., Goodman, Marc T., Thompson, Pamela J., Shvetsov, Yurii B., Runnebaum, Ingo B., Duerst, Matthias, Hillemanns, Peter, Doerk, Thilo, Antonenkova, Natalia, Bogdanova, Natalia, Leminen, Arto, Pelttari, Liisa M., Butzow, Ralf, Modugno, Francesmary, Kelley, Joseph L., Edwards, Robert P., Ness, Roberta B., du Bois, Andreas, Heitz, Florian, Schwaab, Ira, Harter, Philipp, Matsuo, Keitaro, Hosono, Satoyo, Orsulic, Sandra, Jensen, Allan, Kjaer, Susanne Kruger, Hogdall, Estrid, Hasmad, Hanis Nazihah, Azmi, Mat Adenan Noor, Teo, Soo-Hwang, Woo, Yin-Ling, Fridley, Brooke L., Goode, Ellen L., Cunningham, Julie M., Vierkant, Robert A., Bruinsma, Fiona, Giles, Graham G., Liang, Dong, Hildebrandt, Michelle A. T., Wu, Xifeng, Levine, Douglas A., Bisogna, Maria, Berchuck, Andrew, Iversen, Edwin S., Schildkraut, Joellen M., Concannon, Patrick, Weber, Rachel Palmieri, Cramer, Daniel W., Terry, Kathryn L., Poole, Elizabeth M., Tworoger, Shelley S., Bandera, Elisa V., Orlow, Irene, Olson, Sara H., Krakstad, Camilla, Salvesen, Helga B., Tangen, Ingvild L., Bjorge, Line, van Altena, Anne M., Aben, Katja K. H., Kiemeney, Lambertus A., Massuger, Leon F. A. G., Kellar, Melissa, Brooks-Wilson, Angela, Kelemen, Linda E., Cook, Linda S., Le, Nhu D., Cybulski, Cezary, Yang, Hannah, Lissowska, Jolanta, Brinton, Louise A., Wentzensen, Nicolas, Hogdall, Claus, Lundvall, Lene, Nedergaard, Lotte, Baker, Helen, Song, Honglin, Eccles, Diana, McNeish, Ian, Paul, James, Carty, Karen, Siddiqui, Nadeem, Glasspool, Rosalind, Whittemore, Alice S., Rothstein, Joseph H., McGuire, Valerie, Sieh, Weiva, Ji, Bu-Tian, Zheng, Wei, Shu, Xiao-Ou, Gao, Yu-Tang, Rosen, Barry, Risch, Harvey A., McLaughlin, John R., Narod, Steven A., Monteiro, Alvaro N., Chen, Ann, Lin, Hui-Yi, Permuth-Wey, Jenny, Sellers, Thomas A., Tsai, Ya-Yu, Chen, Zhihua, Ziogas, Argyrios, Anton-Culver, Hoda, Gentry-Maharaj, Aleksandra, Menon, Usha, Harrington, Patricia, Lee, Alice W., Wu, Anna H., Pearce, Celeste L., Coetzee, Gerry, Pike, Malcolm C., Dansonka-Mieszkowska, Agnieszka, Timorek, Agnieszka, Rzepecka, Iwona K., Kupryjanczyk, Jolanta, Freedman, Matt, Noushmehr, Houtan, Easton, Douglas F., Offit, Kenneth, Couch, Fergus J., Gayther, Simon, Pharoah, Paul P., Antoniou, Antonis C., and Chenevix-Trench, Georgia
Abstract: Genome-wide association studies (GWAS) have identified 12 epithelial ovarian cancer (EOC) susceptibility alleles. The pattern of association at these loci is consistent in BRCA1 and BRCA2 mutation carriers who are at high risk of EOC. After imputation to 1000 Genomes Project data, we assessed associations of 11 million genetic variants with EOC risk from 15,437 cases unselected for family history and 30,845 controls and from 15,252 BRCA1 mutation carriers and 8,211 BRCA2 mutation carriers (3,096 with ovarian cancer), and we combined the results in a meta-analysis. This new study design yielded increased statistical power, leading to the discovery of six new EOC susceptibility loci. Variants at 1p36 (nearest gene, WNT4), 4q26 (SYNPO2), 9q34.2 (ABO) and 17q11.2 (ATAD5) were associated with EOC risk, and at 1p34.3 (RSPO1) and 6p22.1 (GPX6) variants were specifically associated with the serous EOC subtype, all with P < 5 x 10(-8). Incorporating these variants into risk assessment tools will improve clinical risk predictions for BRCA1 and BRCA2 mutation carriers.
Published: 2015

45. The first targeted therapy in ovarian cancer permitted for BRCA1/2 mutation carriers

Author: Schmutzler, Rita Katharina, Meindl, Alfons, Schmutzler, Rita Katharina, and Meindl, Alfons
Abstract: Olaparib (Lynparza (TM)) is an oral, small-molecule, poly (ADP-ribose) polymerase (PARP) inhibitor being developed by AstraZeneca for the treatment of solid tumours. The primary indication for which olaparib is being developed is BRCA1/2 mutation-positive ovarian cancer. A capsule formulation of the drug has received approval for use in this setting in the EU by the European Medicines Agency (EMA). The application of olaparib has been indicated for germline and somatic mutations in BRCA1 and/or BRCA2 in patients with platinum-sensitive recurrence of serous high-grade ovarian cancer. This requires the analysis of DNA isolated from fresh frozen paraffin-embedded (FFPE) material rather than DNA isolated from blood. However, this therapy-driven switch raises profound technical challenges and intriguing problems in medical care and counselling. For example, decreased sensitivity in mutation detection and a reduced possibility in the evaluation of the variant of unknown significance (VUS) may correlate with inadequate medical care of the patients and their families. Therefore, prospective studies, including the collection of genetic, histopathological and clinical data, are mandatory.
Published: 2015

46. Association of Type and Location ofBRCA1andBRCA2Mutations With Risk of Breast and Ovarian Cancer

Author: Rebbeck, Timothy R., primary, Mitra, Nandita, additional, Wan, Fei, additional, Sinilnikova, Olga M., additional, Healey, Sue, additional, McGuffog, Lesley, additional, Mazoyer, Sylvie, additional, Chenevix-Trench, Georgia, additional, Easton, Douglas F., additional, Antoniou, Antonis C., additional, Nathanson, Katherine L., additional, Laitman, Yael, additional, Kushnir, Anya, additional, Paluch-Shimon, Shani, additional, Berger, Raanan, additional, Zidan, Jamal, additional, Friedman, Eitan, additional, Ehrencrona, Hans, additional, Stenmark-Askmalm, Marie, additional, Einbeigi, Zakaria, additional, Loman, Niklas, additional, Harbst, Katja, additional, Rantala, Johanna, additional, Melin, Beatrice, additional, Huo, Dezheng, additional, Olopade, Olufunmilayo I., additional, Seldon, Joyce, additional, Ganz, Patricia A., additional, Nussbaum, Robert L., additional, Chan, Salina B., additional, Odunsi, Kunle, additional, Gayther, Simon A., additional, Domchek, Susan M., additional, Arun, Banu K., additional, Lu, Karen H., additional, Mitchell, Gillian, additional, Karlan, Beth Y., additional, Walsh, Christine, additional, Lester, Jenny, additional, Godwin, Andrew K., additional, Pathak, Harsh, additional, Ross, Eric, additional, Daly, Mary B., additional, Whittemore, Alice S., additional, John, Esther M., additional, Miron, Alexander, additional, Terry, Mary Beth, additional, Chung, Wendy K., additional, Goldgar, David E., additional, Buys, Saundra S., additional, Janavicius, Ramunas, additional, Tihomirova, Laima, additional, Tung, Nadine, additional, Dorfling, Cecilia M., additional, van Rensburg, Elizabeth J., additional, Steele, Linda, additional, Neuhausen, Susan L., additional, Ding, Yuan Chun, additional, Ejlertsen, Bent, additional, Gerdes, Anne-Marie, additional, Hansen, Thomas v. O., additional, Ramón y Cajal, Teresa, additional, Osorio, Ana, additional, Benitez, Javier, additional, Godino, Javier, additional, Tejada, Maria-Isabel, additional, Duran, Mercedes, additional, Weitzel, Jeffrey N., additional, Bobolis, Kristie A, additional, Sand, Sharon R., additional, Fontaine, Annette, additional, Savarese, Antonella, additional, Pasini, Barbara, additional, Peissel, Bernard, additional, Bonanni, Bernardo, additional, Zaffaroni, Daniela, additional, Vignolo-Lutati, Francesca, additional, Scuvera, Giulietta, additional, Giannini, Giuseppe, additional, Bernard, Loris, additional, Genuardi, Maurizio, additional, Radice, Paolo, additional, Dolcetti, Riccardo, additional, Manoukian, Siranoush, additional, Pensotti, Valeria, additional, Gismondi, Viviana, additional, Yannoukakos, Drakoulis, additional, Fostira, Florentia, additional, Garber, Judy, additional, Torres, Diana, additional, Rashid, Muhammad Usman, additional, Hamann, Ute, additional, Peock, Susan, additional, Frost, Debra, additional, Platte, Radka, additional, Evans, D. Gareth, additional, Eeles, Rosalind, additional, Davidson, Rosemarie, additional, Eccles, Diana, additional, Cole, Trevor, additional, Cook, Jackie, additional, Brewer, Carole, additional, Hodgson, Shirley, additional, Morrison, Patrick J., additional, Walker, Lisa, additional, Porteous, Mary E., additional, Kennedy, M. John, additional, Izatt, Louise, additional, Adlard, Julian, additional, Donaldson, Alan, additional, Ellis, Steve, additional, Sharma, Priyanka, additional, Schmutzler, Rita Katharina, additional, Wappenschmidt, Barbara, additional, Becker, Alexandra, additional, Rhiem, Kerstin, additional, Hahnen, Eric, additional, Engel, Christoph, additional, Meindl, Alfons, additional, Engert, Stefanie, additional, Ditsch, Nina, additional, Arnold, Norbert, additional, Plendl, Hans Jörg, additional, Mundhenke, Christoph, additional, Niederacher, Dieter, additional, Fleisch, Markus, additional, Sutter, Christian, additional, Bartram, C. R., additional, Dikow, Nicola, additional, Wang-Gohrke, Shan, additional, Gadzicki, Dorothea, additional, Steinemann, Doris, additional, Kast, Karin, additional, Beer, Marit, additional, Varon-Mateeva, Raymonda, additional, Gehrig, Andrea, additional, Weber, Bernhard H., additional, Stoppa-Lyonnet, Dominique, additional, Houdayer, Claude, additional, Belotti, Muriel, additional, Gauthier-Villars, Marion, additional, Damiola, Francesca, additional, Boutry-Kryza, Nadia, additional, Lasset, Christine, additional, Sobol, Hagay, additional, Peyrat, Jean-Philippe, additional, Muller, Danièle, additional, Fricker, Jean-Pierre, additional, Collonge-Rame, Marie-Agnès, additional, Mortemousque, Isabelle, additional, Nogues, Catherine, additional, Rouleau, Etienne, additional, Isaacs, Claudine, additional, De Paepe, Anne, additional, Poppe, Bruce, additional, Claes, Kathleen, additional, De Leeneer, Kim, additional, Piedmonte, Marion, additional, Rodriguez, Gustavo, additional, Wakely, Katie, additional, Boggess, John, additional, Blank, Stephanie V., additional, Basil, Jack, additional, Azodi, Masoud, additional, Phillips, Kelly-Anne, additional, Caldes, Trinidad, additional, de la Hoya, Miguel, additional, Romero, Atocha, additional, Nevanlinna, Heli, additional, Aittomäki, Kristiina, additional, van der Hout, Annemarie H., additional, Hogervorst, Frans B. L., additional, Verhoef, Senno, additional, Collée, J. Margriet, additional, Seynaeve, Caroline, additional, Oosterwijk, Jan C., additional, Gille, Johannes J. P., additional, Wijnen, Juul T., additional, Garcia, Encarna B. Gómez, additional, Kets, Carolien M., additional, Ausems, Margreet G. E. M., additional, Aalfs, Cora M., additional, Devilee, Peter, additional, Mensenkamp, Arjen R., additional, Kwong, Ava, additional, Olah, Edith, additional, Papp, Janos, additional, Diez, Orland, additional, Lazaro, Conxi, additional, Darder, Esther, additional, Blanco, Ignacio, additional, Salinas, Mónica, additional, Jakubowska, Anna, additional, Lubinski, Jan, additional, Gronwald, Jacek, additional, Jaworska-Bieniek, Katarzyna, additional, Durda, Katarzyna, additional, Sukiennicki, Grzegorz, additional, Huzarski, Tomasz, additional, Byrski, Tomasz, additional, Cybulski, Cezary, additional, Toloczko-Grabarek, Aleksandra, additional, Zlowocka-Perlowska, Elzbieta, additional, Menkiszak, Janusz, additional, Arason, Adalgeir, additional, Barkardottir, Rosa B., additional, Simard, Jacques, additional, Laframboise, Rachel, additional, Montagna, Marco, additional, Agata, Simona, additional, Alducci, Elisa, additional, Peixoto, Ana, additional, Teixeira, Manuel R., additional, Spurdle, Amanda B., additional, Lee, Min Hyuk, additional, Park, Sue K., additional, Kim, Sung-Won, additional, Friebel, Tara M., additional, Couch, Fergus J., additional, Lindor, Noralane M., additional, Pankratz, Vernon S., additional, Guidugli, Lucia, additional, Wang, Xianshu, additional, Tischkowitz, Marc, additional, Foretova, Lenka, additional, Vijai, Joseph, additional, Offit, Kenneth, additional, Robson, Mark, additional, Rau-Murthy, Rohini, additional, Kauff, Noah, additional, Fink-Retter, Anneliese, additional, Singer, Christian F., additional, Rappaport, Christine, additional, Gschwantler-Kaulich, Daphne, additional, Pfeiler, Georg, additional, Tea, Muy-Kheng, additional, Berger, Andreas, additional, Greene, Mark H., additional, Mai, Phuong L., additional, Imyanitov, Evgeny N., additional, Toland, Amanda Ewart, additional, Senter, Leigha, additional, Bojesen, Anders, additional, Pedersen, Inge Sokilde, additional, Skytte, Anne-Bine, additional, Sunde, Lone, additional, Thomassen, Mads, additional, Moeller, Sanne Traasdahl, additional, Kruse, Torben A., additional, Jensen, Uffe Birk, additional, Caligo, Maria Adelaide, additional, Aretini, Paolo, additional, Teo, Soo-Hwang, additional, Selkirk, Christina G., additional, Hulick, Peter J., additional, and Andrulis, Irene, additional
Published: 2015
Full Text: View/download PDF

47. Refined histopathological predictors of BRCA1 and BRCA2 mutation status: a large-scale analysis of breast cancer characteristics from the BCAC, CIMBA, and ENIGMA consortia

Author: Spurdle, Amanda B., Couch, Fergus J., Parsons, Michael T., McGuffog, Lesley, Barrowdale, Daniel, Bolla, Manjeet K., Wang, Qin, Healey, Sue, Schmutzler, Rita Katharina, Wappenschmidt, Barbara, Rhiem, Kerstin, Hahnen, Eric, Engel, Christoph, Meindl, Alfons, Ditsch, Nina, Arnold, Norbert, Plendl, Hansjoerg, Niederacher, Dieter, Sutter, Christian, Wang-Gohrke, Shan, Steinemann, Doris, Preisler-Adams, Sabine, Kast, Karin, Varon-Mateeva, Raymonda, Ellis, Steve, Frost, Debra, Platte, Radka, Perkins, Jo, Evans, D. Gareth, Izatt, Louise, Eeles, Ros, Adlard, Julian, Davidson, Rosemarie, Cole, Trevor, Scuvera, Giulietta, Manoukian, Siranoush, Bonanni, Bernardo, Mariette, Frederique, Fortuzzi, Stefano, Viel, Alessandra, Pasini, Barbara, Papi, Laura, Varesco, Liliana, Balleine, Rosemary, Nathanson, Katherine L., Domchek, Susan M., Offitt, Kenneth, Jakubowska, Anna, Lindor, Noralane, Thomassen, Mads, Jensen, Uffe Birk, Rantala, Johanna, Borg, Ake, Andrulis, Irene L., Miron, Alexander, Hansen, Thomas V. O., Caldes, Trinidad, Neuhausen, Susan L., Toland, Amanda E., Nevanlinna, Heli, Montagna, Marco, Garber, Judy, Godwin, Andrew K., Osorio, Ana, Factor, Rachel E., Terry, Mary B., Rebbeck, Timothy R., Karlan, Beth Y., Southey, Melissa, Rashid, Muhammad Usman, Tung, Nadine, Pharoah, Paul D. P., Blows, Fiona M., Dunning, Alison M., Provenzano, Elena, Hall, Per, Czene, Kamila, Schmidt, Marjanka K., Broeks, Annegien, Cornelissen, Sten, Verhoef, Senno, Fasching, Peter A., Beckmann, Matthias W., Ekici, Arif B., Slamon, Dennis J., Bojesen, Stig E., Nordestgaard, Borge G., Nielsen, Sune F., Flyger, Henrik, Chang-Claude, Jenny, Flesch-Janys, Dieter, Rudolph, Anja, Seibold, Petra, Aittomaki, Kristiina, Muranen, Taru A., Heikkila, Paivi, Blomqvist, Carl, Figueroa, Jonine, Chanock, Stephen J., Brinton, Louise, Lissowska, Jolanta, Olson, Janet E., Pankratz, Vernon S., John, Esther M., Whittemore, Alice S., West, Dee W., Hamann, Ute, Torres, Diana, Ulmer, Hans Ulrich, Rudiger, Thomas, Devilee, Peter, Tollenaar, Robert A. E. M., Seynaeve, Caroline, Van Asperen, Christi J., Eccles, Diana M., Tapper, William J., Durcan, Lorraine, Jones, Louise, Peto, Julian, dos-Santos-Silva, Isabel, Fletcher, Olivia, Johnson, Nichola, Dwek, Miriam, Swann, Ruth, Bane, Anita L., Glendon, Gord, Mulligan, Anna M., Giles, Graham G., Milne, Roger L., Baglietto, Laura, McLean, Catriona, Carpenter, Jane, Clarke, Christine, Scott, Rodney, Brauch, Hiltrud, Bruning, Thomas, Ko, Yon-Dschun, Cox, Angela, Cross, Simon S., Reed, Malcolm W. R., Lubinski, Jan, Jaworska-Bieniek, Katarzyna, Durda, Katarzyna, Gronwald, Jacek, Dork, Thilo, Bogdanova, Natalia, Park-Simon, Tjoung-Won, Hillemanns, Peter, Haiman, Christopher A., Henderson, Brian E., Schumacher, Fredrick, Le Marchand, Loic, Burwinkel, Barbara, Marme, Frederik, Surovy, Harald, Yang, Rongxi, Anton-Culver, Hoda, Ziogas, Argyrios, Hooning, Maartje J., Collee, J. Margriet, Martens, John W. M., Tilanus-Linthorst, Madeleine M. A., Brenner, Hermann, Dieffenbach, Aida Karina, Arndt, Volke, Stegmaier, Christa, Winqvist, Robert, Pylkas, Katri, Jukkola-Vuorinen, Arja, Grip, Mervi, Lindblom, Annika, Margolin, Sara, Joseph, Vijai, Robson, Mark, Rau-Murthy, Rohini, Gonzalez-Neira, Anna, Arias, Jose Ignacio, Zamora, Pilar, Benitez, Javier, Mannermaa, Arto, Kataja, Vesa, Kosma, Veli-Matti, Hartikainen, Jaana M., Peterlongo, Paolo, Zaffaroni, Daniela, Barile, Monica, Capra, Fabio, Radice, Paolo, Teo, Soo H., Easton, Douglas F., Antoniou, Antonis C., Chenevix-Trench, Georgia, Goldgar, David E., Spurdle, Amanda B., Couch, Fergus J., Parsons, Michael T., McGuffog, Lesley, Barrowdale, Daniel, Bolla, Manjeet K., Wang, Qin, Healey, Sue, Schmutzler, Rita Katharina, Wappenschmidt, Barbara, Rhiem, Kerstin, Hahnen, Eric, Engel, Christoph, Meindl, Alfons, Ditsch, Nina, Arnold, Norbert, Plendl, Hansjoerg, Niederacher, Dieter, Sutter, Christian, Wang-Gohrke, Shan, Steinemann, Doris, Preisler-Adams, Sabine, Kast, Karin, Varon-Mateeva, Raymonda, Ellis, Steve, Frost, Debra, Platte, Radka, Perkins, Jo, Evans, D. Gareth, Izatt, Louise, Eeles, Ros, Adlard, Julian, Davidson, Rosemarie, Cole, Trevor, Scuvera, Giulietta, Manoukian, Siranoush, Bonanni, Bernardo, Mariette, Frederique, Fortuzzi, Stefano, Viel, Alessandra, Pasini, Barbara, Papi, Laura, Varesco, Liliana, Balleine, Rosemary, Nathanson, Katherine L., Domchek, Susan M., Offitt, Kenneth, Jakubowska, Anna, Lindor, Noralane, Thomassen, Mads, Jensen, Uffe Birk, Rantala, Johanna, Borg, Ake, Andrulis, Irene L., Miron, Alexander, Hansen, Thomas V. O., Caldes, Trinidad, Neuhausen, Susan L., Toland, Amanda E., Nevanlinna, Heli, Montagna, Marco, Garber, Judy, Godwin, Andrew K., Osorio, Ana, Factor, Rachel E., Terry, Mary B., Rebbeck, Timothy R., Karlan, Beth Y., Southey, Melissa, Rashid, Muhammad Usman, Tung, Nadine, Pharoah, Paul D. P., Blows, Fiona M., Dunning, Alison M., Provenzano, Elena, Hall, Per, Czene, Kamila, Schmidt, Marjanka K., Broeks, Annegien, Cornelissen, Sten, Verhoef, Senno, Fasching, Peter A., Beckmann, Matthias W., Ekici, Arif B., Slamon, Dennis J., Bojesen, Stig E., Nordestgaard, Borge G., Nielsen, Sune F., Flyger, Henrik, Chang-Claude, Jenny, Flesch-Janys, Dieter, Rudolph, Anja, Seibold, Petra, Aittomaki, Kristiina, Muranen, Taru A., Heikkila, Paivi, Blomqvist, Carl, Figueroa, Jonine, Chanock, Stephen J., Brinton, Louise, Lissowska, Jolanta, Olson, Janet E., Pankratz, Vernon S., John, Esther M., Whittemore, Alice S., West, Dee W., Hamann, Ute, Torres, Diana, Ulmer, Hans Ulrich, Rudiger, Thomas, Devilee, Peter, Tollenaar, Robert A. E. M., Seynaeve, Caroline, Van Asperen, Christi J., Eccles, Diana M., Tapper, William J., Durcan, Lorraine, Jones, Louise, Peto, Julian, dos-Santos-Silva, Isabel, Fletcher, Olivia, Johnson, Nichola, Dwek, Miriam, Swann, Ruth, Bane, Anita L., Glendon, Gord, Mulligan, Anna M., Giles, Graham G., Milne, Roger L., Baglietto, Laura, McLean, Catriona, Carpenter, Jane, Clarke, Christine, Scott, Rodney, Brauch, Hiltrud, Bruning, Thomas, Ko, Yon-Dschun, Cox, Angela, Cross, Simon S., Reed, Malcolm W. R., Lubinski, Jan, Jaworska-Bieniek, Katarzyna, Durda, Katarzyna, Gronwald, Jacek, Dork, Thilo, Bogdanova, Natalia, Park-Simon, Tjoung-Won, Hillemanns, Peter, Haiman, Christopher A., Henderson, Brian E., Schumacher, Fredrick, Le Marchand, Loic, Burwinkel, Barbara, Marme, Frederik, Surovy, Harald, Yang, Rongxi, Anton-Culver, Hoda, Ziogas, Argyrios, Hooning, Maartje J., Collee, J. Margriet, Martens, John W. M., Tilanus-Linthorst, Madeleine M. A., Brenner, Hermann, Dieffenbach, Aida Karina, Arndt, Volke, Stegmaier, Christa, Winqvist, Robert, Pylkas, Katri, Jukkola-Vuorinen, Arja, Grip, Mervi, Lindblom, Annika, Margolin, Sara, Joseph, Vijai, Robson, Mark, Rau-Murthy, Rohini, Gonzalez-Neira, Anna, Arias, Jose Ignacio, Zamora, Pilar, Benitez, Javier, Mannermaa, Arto, Kataja, Vesa, Kosma, Veli-Matti, Hartikainen, Jaana M., Peterlongo, Paolo, Zaffaroni, Daniela, Barile, Monica, Capra, Fabio, Radice, Paolo, Teo, Soo H., Easton, Douglas F., Antoniou, Antonis C., Chenevix-Trench, Georgia, and Goldgar, David E.
Abstract: Introduction: The distribution of histopathological features of invasive breast tumors in BRCA1 or BRCA2 germline mutation carriers differs from that of individuals with no known mutation. Histopathological features thus have utility for mutation prediction, including statistical modeling to assess pathogenicity of BRCA1 or BRCA2 variants of uncertain clinical significance. We analyzed large pathology datasets accrued by the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) and the Breast Cancer Association Consortium (BCAC) to reassess histopathological predictors of BRCA1 and BRCA2 mutation status, and provide robust likelihood ratio (LR) estimates for statistical modeling. Methods: Selection criteria for study/center inclusion were estrogen receptor (ER) status or grade data available for invasive breast cancer diagnosed younger than 70 years. The dataset included 4,477 BRCA1 mutation carriers, 2,565 BRCA2 mutation carriers, and 47,565 BCAC breast cancer cases. Country-stratified estimates of the likelihood of mutation status by histopathological markers were derived using a Mantel-Haenszel approach. Results: ER-positive phenotype negatively predicted BRCA1 mutation status, irrespective of grade (LRs from 0.08 to 0.90). ER-negative grade 3 histopathology was more predictive of positive BRCA1 mutation status in women 50 years or older (LR = 4.13 (3.70 to 4.62)) versus younger than 50 years (LR = 3.16 (2.96 to 3.37)). For BRCA2, ER-positive grade 3 phenotype modestly predicted positive mutation status irrespective of age (LR = 1.7-fold), whereas ER-negative grade 3 features modestly predicted positive mutation status at 50 years or older (LR = 1.54 (1.27 to 1.88)). Triple-negative tumor status was highly predictive of BRCA1 mutation status for women younger than 50 years (LR = 3.73 (3.43 to 4.05)) and 50 years or older (LR = 4.41 (3.86 to 5.04)), and modestly predictive of positive BRCA2 mutation status in women 50 years or older (LR = 1.79 (1.42 to 2.24)
Published: 2014

48. Pathological features of breast and ovarian cancers in RAD51C germline mutation carriers

Author: Gevensleben, Heidrun, Bossung, Verena, Meindl, Alfons, Wappenschmidt, Barbara, de Gregorio, Nikolaus, Osorio, Ana, Romero, Atocha, Buettner, Reinhard, Markiefka, Birgid, Schmutzler, Rita Katharina, Gevensleben, Heidrun, Bossung, Verena, Meindl, Alfons, Wappenschmidt, Barbara, de Gregorio, Nikolaus, Osorio, Ana, Romero, Atocha, Buettner, Reinhard, Markiefka, Birgid, and Schmutzler, Rita Katharina
Published: 2014

49. Hereditary Breast Cancer

Author: Schmutzler, Rita Katharina, primary
Full Text: View/download PDF

50. Präventives Versorgungskonzept bei erblichem Brustkrebs

Author: Rhiem, Kerstin, primary and Schmutzler, Rita Katharina, additional
Full Text: View/download PDF

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