Author: "Senno Verhoef" - Searchworks@Jio Institute Digital Library Search Results

Your search keyword '"Senno Verhoef"' showing total 97 results

Start Over Author "Senno Verhoef"

97 results on '"Senno Verhoef"'

1. Genetically Predicted Body Mass Index and Breast Cancer Risk: Mendelian Randomization Analyses of Data from 145,000 Women of European Descent.

Author: Yan Guo, Shaneda Warren Andersen, Xiao-Ou Shu, Kyriaki Michailidou, Manjeet K Bolla, Qin Wang, Montserrat Garcia-Closas, Roger L Milne, Marjanka K Schmidt, Jenny Chang-Claude, Allison Dunning, Stig E Bojesen, Habibul Ahsan, Kristiina Aittomäki, Irene L Andrulis, Hoda Anton-Culver, Volker Arndt, Matthias W Beckmann, Alicia Beeghly-Fadiel, Javier Benitez, Natalia V Bogdanova, Bernardo Bonanni, Anne-Lise Børresen-Dale, Judith Brand, Hiltrud Brauch, Hermann Brenner, Thomas Brüning, Barbara Burwinkel, Graham Casey, Georgia Chenevix-Trench, Fergus J Couch, Angela Cox, Simon S Cross, Kamila Czene, Peter Devilee, Thilo Dörk, Martine Dumont, Peter A Fasching, Jonine Figueroa, Dieter Flesch-Janys, Olivia Fletcher, Henrik Flyger, Florentia Fostira, Marilie Gammon, Graham G Giles, Pascal Guénel, Christopher A Haiman, Ute Hamann, Maartje J Hooning, John L Hopper, Anna Jakubowska, Farzana Jasmine, Mark Jenkins, Esther M John, Nichola Johnson, Michael E Jones, Maria Kabisch, Muhammad Kibriya, Julia A Knight, Linetta B Koppert, Veli-Matti Kosma, Vessela Kristensen, Loic Le Marchand, Eunjung Lee, Jingmei Li, Annika Lindblom, Robert Luben, Jan Lubinski, Kathi E Malone, Arto Mannermaa, Sara Margolin, Frederik Marme, Catriona McLean, Hanne Meijers-Heijboer, Alfons Meindl, Susan L Neuhausen, Heli Nevanlinna, Patrick Neven, Janet E Olson, Jose I A Perez, Barbara Perkins, Paolo Peterlongo, Kelly-Anne Phillips, Katri Pylkäs, Anja Rudolph, Regina Santella, Elinor J Sawyer, Rita K Schmutzler, Caroline Seynaeve, Mitul Shah, Martha J Shrubsole, Melissa C Southey, Anthony J Swerdlow, Amanda E Toland, Ian Tomlinson, Diana Torres, Thérèse Truong, Giske Ursin, Rob B Van Der Luijt, Senno Verhoef, Alice S Whittemore, Robert Winqvist, Hui Zhao, Shilin Zhao, Per Hall, Jacques Simard, Peter Kraft, Paul Pharoah, David Hunter, Douglas F Easton, and Wei Zheng
Subjects: Medicine
Abstract: BackgroundObservational epidemiological studies have shown that high body mass index (BMI) is associated with a reduced risk of breast cancer in premenopausal women but an increased risk in postmenopausal women. It is unclear whether this association is mediated through shared genetic or environmental factors.MethodsWe applied Mendelian randomization to evaluate the association between BMI and risk of breast cancer occurrence using data from two large breast cancer consortia. We created a weighted BMI genetic score comprising 84 BMI-associated genetic variants to predicted BMI. We evaluated genetically predicted BMI in association with breast cancer risk using individual-level data from the Breast Cancer Association Consortium (BCAC) (cases = 46,325, controls = 42,482). We further evaluated the association between genetically predicted BMI and breast cancer risk using summary statistics from 16,003 cases and 41,335 controls from the Discovery, Biology, and Risk of Inherited Variants in Breast Cancer (DRIVE) Project. Because most studies measured BMI after cancer diagnosis, we could not conduct a parallel analysis to adequately evaluate the association of measured BMI with breast cancer risk prospectively.ResultsIn the BCAC data, genetically predicted BMI was found to be inversely associated with breast cancer risk (odds ratio [OR] = 0.65 per 5 kg/m2 increase, 95% confidence interval [CI]: 0.56-0.75, p = 3.32 × 10-10). The associations were similar for both premenopausal (OR = 0.44, 95% CI:0.31-0.62, p = 9.91 × 10-8) and postmenopausal breast cancer (OR = 0.57, 95% CI: 0.46-0.71, p = 1.88 × 10-8). This association was replicated in the data from the DRIVE consortium (OR = 0.72, 95% CI: 0.60-0.84, p = 1.64 × 10-7). Single marker analyses identified 17 of the 84 BMI-associated single nucleotide polymorphisms (SNPs) in association with breast cancer risk at p ConclusionsBMI predicted by genome-wide association studies (GWAS)-identified variants is inversely associated with the risk of both pre- and postmenopausal breast cancer. The reduced risk of postmenopausal breast cancer associated with genetically predicted BMI observed in this study differs from the positive association reported from studies using measured adult BMI. Understanding the reasons for this discrepancy may reveal insights into the complex relationship of genetic determinants of body weight in the etiology of breast cancer.
Published: 2016
Full Text: View/download PDF

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

Author: Fergus J Couch, Xianshu Wang, Lesley McGuffog, Andrew Lee, Curtis Olswold, Karoline B Kuchenbaecker, Penny Soucy, Zachary Fredericksen, Daniel Barrowdale, Joe Dennis, Mia M Gaudet, Ed Dicks, Matthew Kosel, Sue Healey, Olga M Sinilnikova, Adam Lee, François Bacot, Daniel Vincent, Frans B L Hogervorst, Susan Peock, Dominique Stoppa-Lyonnet, Anna Jakubowska, kConFab Investigators, Paolo Radice, Rita Katharina Schmutzler, SWE-BRCA, Susan M Domchek, Marion Piedmonte, Christian F Singer, Eitan Friedman, Mads Thomassen, Ontario Cancer Genetics Network, Thomas V O Hansen, Susan L Neuhausen, Csilla I Szabo, Ignacio Blanco, Mark H Greene, Beth Y Karlan, Judy Garber, Catherine M Phelan, Jeffrey N Weitzel, Marco Montagna, Edith Olah, Irene L Andrulis, Andrew K Godwin, Drakoulis Yannoukakos, David E Goldgar, Trinidad Caldes, Heli Nevanlinna, Ana Osorio, Mary Beth Terry, Mary B Daly, Elizabeth J van Rensburg, Ute Hamann, Susan J Ramus, Amanda Ewart Toland, Maria A Caligo, Olufunmilayo I Olopade, Nadine Tung, Kathleen Claes, Mary S Beattie, Melissa C Southey, Evgeny N Imyanitov, Marc Tischkowitz, Ramunas Janavicius, Esther M John, Ava Kwong, Orland Diez, Judith Balmaña, Rosa B Barkardottir, Banu K Arun, Gad Rennert, Soo-Hwang Teo, Patricia A Ganz, Ian Campbell, Annemarie H van der Hout, Carolien H M van Deurzen, Caroline Seynaeve, Encarna B Gómez Garcia, Flora E van Leeuwen, Hanne E J Meijers-Heijboer, Johannes J P Gille, Margreet G E M Ausems, Marinus J Blok, Marjolijn J L Ligtenberg, Matti A Rookus, Peter Devilee, Senno Verhoef, Theo A M van Os, Juul T Wijnen, HEBON, EMBRACE, Debra Frost, Steve Ellis, Elena Fineberg, Radka Platte, D Gareth Evans, Louise Izatt, Rosalind A Eeles, Julian Adlard, Diana M Eccles, Jackie Cook, Carole Brewer, Fiona Douglas, Shirley Hodgson, Patrick J Morrison, Lucy E Side, Alan Donaldson, Catherine Houghton, Mark T Rogers, Huw Dorkins, Jacqueline Eason, Helen Gregory, Emma McCann, Alex Murray, Alain Calender, Agnès Hardouin, Pascaline Berthet, Capucine Delnatte, Catherine Nogues, Christine Lasset, Claude Houdayer, Dominique Leroux, Etienne Rouleau, Fabienne Prieur, Francesca Damiola, Hagay Sobol, Isabelle Coupier, Laurence Venat-Bouvet, Laurent Castera, Marion Gauthier-Villars, Mélanie Léoné, Pascal Pujol, Sylvie Mazoyer, Yves-Jean Bignon, GEMO Study Collaborators, Elżbieta Złowocka-Perłowska, Jacek Gronwald, Jan Lubinski, Katarzyna Durda, Katarzyna Jaworska, Tomasz Huzarski, Amanda B Spurdle, Alessandra Viel, Bernard Peissel, Bernardo Bonanni, Giulia Melloni, Laura Ottini, Laura Papi, Liliana Varesco, Maria Grazia Tibiletti, Paolo Peterlongo, Sara Volorio, Siranoush Manoukian, Valeria Pensotti, Norbert Arnold, Christoph Engel, Helmut Deissler, Dorothea Gadzicki, Andrea Gehrig, Karin Kast, Kerstin Rhiem, Alfons Meindl, Dieter Niederacher, Nina Ditsch, Hansjoerg Plendl, Sabine Preisler-Adams, Stefanie Engert, Christian Sutter, Raymonda Varon-Mateeva, Barbara Wappenschmidt, Bernhard H F Weber, Brita Arver, Marie Stenmark-Askmalm, Niklas Loman, Richard Rosenquist, Zakaria Einbeigi, Katherine L Nathanson, Timothy R Rebbeck, Stephanie V Blank, David E Cohn, Gustavo C Rodriguez, Laurie Small, Michael Friedlander, Victoria L Bae-Jump, Anneliese Fink-Retter, Christine Rappaport, Daphne Gschwantler-Kaulich, Georg Pfeiler, Muy-Kheng Tea, Noralane M Lindor, Bella Kaufman, Shani Shimon Paluch, Yael Laitman, Anne-Bine Skytte, Anne-Marie Gerdes, Inge Sokilde Pedersen, Sanne Traasdahl Moeller, Torben A Kruse, Uffe Birk Jensen, Joseph Vijai, Kara Sarrel, Mark Robson, Noah Kauff, Anna Marie Mulligan, Gord Glendon, Hilmi Ozcelik, Bent Ejlertsen, Finn C Nielsen, Lars Jønson, Mette K Andersen, Yuan Chun Ding, Linda Steele, Lenka Foretova, Alex Teulé, Conxi Lazaro, Joan Brunet, Miquel Angel Pujana, Phuong L Mai, Jennifer T Loud, Christine Walsh, Jenny Lester, Sandra Orsulic, Steven A Narod, Josef Herzog, Sharon R Sand, Silvia Tognazzo, Simona Agata, Tibor Vaszko, Joellen Weaver, Alexandra V Stavropoulou, Saundra S Buys, Atocha Romero, Miguel de la Hoya, Kristiina Aittomäki, Taru A Muranen, Mercedes Duran, Wendy K Chung, Adriana Lasa, Cecilia M Dorfling, Alexander Miron, BCFR, Javier Benitez, Leigha Senter, Dezheng Huo, Salina B Chan, Anna P Sokolenko, Jocelyne Chiquette, Laima Tihomirova, Tara M Friebel, Bjarni A Agnarsson, Karen H Lu, Flavio Lejbkowicz, Paul A James, Per Hall, Alison M Dunning, Daniel Tessier, Julie Cunningham, Susan L Slager, Chen Wang, Steven Hart, Kristen Stevens, Jacques Simard, Tomi Pastinen, Vernon S Pankratz, Kenneth Offit, Douglas F Easton, Georgia Chenevix-Trench, Antonis C Antoniou, and CIMBA
Subjects: Genetics, QH426-470
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
Full Text: View/download PDF

3. Supplementary Materials and Methods, Tables 1-5 from Common Breast Cancer Susceptibility Loci Are Associated with Triple-Negative Breast Cancer

Author: Fergus J. Couch, Xianshu Wang, Heli Nevanlinna, Drakoulis Yannoukakos, Jenny Chang-Claude, Douglas F. Easton, Paul Pharoah, Ute Hamann, Gianluca Severi, Isabel dos Santos Silva, Diether Lambrechts, Grant W. Montgomery, Nicholas G. Martin, Arto Mannermaa, Sara Margolin, Sarah-Jane Dawson, Fiona M. Blows, Jianjun Liu, Astrid Irwanto, Carl Blomqvist, Dario Greco, Jonathan Beesley, Veli-Matti Kosma, Ian Tomlinson, Senno Verhoef, Laura Baglietto, Graham G. Giles, Olivia Fletcher, Julian Peto, Hilde Janssen, Erik Van Limbergen, Yon-Dschun Ko, Arja Jukkola-Vuorinen, Katri Pylkäs, Swati Kulkarni, Foluso Ademuyiwa, Thomas Dünnebier, Asta Försti, Thomas Rüdiger, JoEllen Weaver, Eric Ross, Harsh Pathak, Robert B. Diasio, Zachary Fredericksen, Janet E. Olson, Rosemary Balleine, Christine L. Clarke, George Fountzilas, Athanasios M. Dimopoulos, Dimitrios Pectasides, Florentia Fostira, Irene Konstantopoulou, Hans-Peter Sinn, Judith Heinz, Dieter Flesch-Janys, Stephan Nickels, Rebecca Hein, Nikki Graham, Lorraine Durcan, Susan M. Gerty, William J. Tapper, Arif B. Ekici, Rüdiger Schulz-Wendtland, Matthias W. Beckmann, Arndt Hartmann, Elinor Sawyer, Simon S. Cross, Angela Cox, Marjanka K. Schmidt, Hiltrud Brauch, Robert Winqvist, Christine Ambrosone, Andrew K. Godwin, Jane E. Carpenter, Diana Eccles, Penelope Miron, Peter A. Fasching, Curtis Olswold, Timothy Lesnick, Susan Slager, Adam M. Lee, Celine M. Vachon, and Kristen N. Stevens
Abstract: PDDF file - 167K
Published: 2023
Full Text: View/download PDF

4. Additional file 8 of Exploring the link between MORF4L1 and risk of breast cancer

Author: Martrat, Griselda, Maxwell, Christopher A, Tominaga, Emiko, Porta-De-La-Riva, Montserrat, Bonifaci, Núria, Gómez-Baldó, Laia, Bogliolo, Massimo, Conxi Lázaro, Blanco, Ignacio, Brunet, Joan, Aguilar, Helena, Fernández-Rodríguez, Juana, Seal, Sheila, Renwick, Anthony, Nazneen Rahman, Kühl, Julia, Neveling, Kornelia, Schindler, Detlev, Ramírez, María J, Castellà, María, Hernández, Gonzalo, Easton, Douglas F, Peock, Susan, Cook, Margaret, Oliver, Clare T, Frost, Debra, Platte, Radka, D Gareth Evans, Lalloo, Fiona, Eeles, Rosalind, Izatt, Louise, Chu, Carol, Davidson, Rosemarie, Kai-Ren Ong, Cook, Jackie, Douglas, Fiona, Hodgson, Shirley, Brewer, Carole, Morrison, Patrick J, Porteous, Mary, Peterlongo, Paolo, Manoukian, Siranoush, Peissel, Bernard, Zaffaroni, Daniela, Roversi, Gaia, Barile, Monica, Viel, Alessandra, Pasini, Barbara, Ottini, Laura, Putignano, Anna Laura, Savarese, Antonella, Bernard, Loris, Radice, Paolo, Healey, Sue, Spurdle, Amanda, Xiaoqing Chen, Beesley, Jonathan, Rookus, Matti A, Senno Verhoef, Tilanus-Linthorst, Madeleine A, Vreeswijk, Maaike P, Asperen, Christi J, Bodmer, Danielle, Ausems, Margreet GEM, Os, Theo A Van, Blok, Marinus J, Meijers-Heijboer, Hanne EJ, Hogervorst, Frans BL, Goldgar, David E, Buys, Saundra, John, Esther M, Miron, Alexander, Southey, Melissa, Daly, Mary B, Harbst, Katja, Borg, Åke, Rantala, Johanna, Barbany-Bustinza, Gisela, Ehrencrona, Hans, Stenmark-Askmalm, Marie, Kaufman, Bella, Laitman, Yael, Milgrom, Roni, Friedman, Eitan, Domchek, Susan M, Nathanson, Katherine L, Rebbeck, Timothy R, Johannsson, Oskar Thor, Couch, Fergus J, Xianshu Wang, Fredericksen, Zachary, Cuadras, Daniel, Moreno, Víctor, Pientka, Friederike K, Depping, Reinhard, Caldés, Trinidad, Osorio, Ana, Benítez, Javier, Bueren, Juan, Heikkinen, Tuomas, Nevanlinna, Heli, Hamann, Ute, Torres, Diana, Caligo, Maria Adelaide, Godwin, Andrew K, Imyanitov, Evgeny N, Ramunas Janavicius, Sinilnikova, Olga M, Stoppa-Lyonnet, Dominique, Mazoyer, Sylvie, Verny-Pierre, Carole, Castera, Laurent, Pauw, Antoine De, Yves-Jean Bignon, Uhrhammer, Nancy, Jean-Philippe Peyrat, Vennin, Philippe, Ferrer, Sandra Fert, Marie-Agnès Collonge-Rame, Mortemousque, Isabelle, McGuffog, Lesley, Chenevix-Trench, Georgia, Pereira-Smith, Olivia M, Antoniou, Antonis C, Cerón, Julián, Tominaga, Kaoru, Surrallés, Jordi, and Pujana, Miguel Angel
Abstract: Additional file 8: Co-AP assays involving MRG15 and MRGX. Supplementary Figure 4 containing results of co-AP assays involving MRG15 and MRGX. (PDF 1 MB)
Published: 2020
Full Text: View/download PDF

5. Additional file 7 of Exploring the link between MORF4L1 and risk of breast cancer

Author: Martrat, Griselda, Maxwell, Christopher A, Tominaga, Emiko, Porta-De-La-Riva, Montserrat, Bonifaci, Núria, Gómez-Baldó, Laia, Bogliolo, Massimo, Conxi Lázaro, Blanco, Ignacio, Brunet, Joan, Aguilar, Helena, Fernández-Rodríguez, Juana, Seal, Sheila, Renwick, Anthony, Nazneen Rahman, Kühl, Julia, Neveling, Kornelia, Schindler, Detlev, Ramírez, María J, Castellà, María, Hernández, Gonzalo, Easton, Douglas F, Peock, Susan, Cook, Margaret, Oliver, Clare T, Frost, Debra, Platte, Radka, D Gareth Evans, Lalloo, Fiona, Eeles, Rosalind, Izatt, Louise, Chu, Carol, Davidson, Rosemarie, Kai-Ren Ong, Cook, Jackie, Douglas, Fiona, Hodgson, Shirley, Brewer, Carole, Morrison, Patrick J, Porteous, Mary, Peterlongo, Paolo, Manoukian, Siranoush, Peissel, Bernard, Zaffaroni, Daniela, Roversi, Gaia, Barile, Monica, Viel, Alessandra, Pasini, Barbara, Ottini, Laura, Putignano, Anna Laura, Savarese, Antonella, Bernard, Loris, Radice, Paolo, Healey, Sue, Spurdle, Amanda, Xiaoqing Chen, Beesley, Jonathan, Rookus, Matti A, Senno Verhoef, Tilanus-Linthorst, Madeleine A, Vreeswijk, Maaike P, Asperen, Christi J, Bodmer, Danielle, Ausems, Margreet GEM, Os, Theo A Van, Blok, Marinus J, Meijers-Heijboer, Hanne EJ, Hogervorst, Frans BL, Goldgar, David E, Buys, Saundra, John, Esther M, Miron, Alexander, Southey, Melissa, Daly, Mary B, Harbst, Katja, Borg, Åke, Rantala, Johanna, Barbany-Bustinza, Gisela, Ehrencrona, Hans, Stenmark-Askmalm, Marie, Kaufman, Bella, Laitman, Yael, Milgrom, Roni, Friedman, Eitan, Domchek, Susan M, Nathanson, Katherine L, Rebbeck, Timothy R, Johannsson, Oskar Thor, Couch, Fergus J, Xianshu Wang, Fredericksen, Zachary, Cuadras, Daniel, Moreno, Víctor, Pientka, Friederike K, Depping, Reinhard, Caldés, Trinidad, Osorio, Ana, Benítez, Javier, Bueren, Juan, Heikkinen, Tuomas, Nevanlinna, Heli, Hamann, Ute, Torres, Diana, Caligo, Maria Adelaide, Godwin, Andrew K, Imyanitov, Evgeny N, Ramunas Janavicius, Sinilnikova, Olga M, Stoppa-Lyonnet, Dominique, Mazoyer, Sylvie, Verny-Pierre, Carole, Castera, Laurent, Pauw, Antoine De, Yves-Jean Bignon, Uhrhammer, Nancy, Jean-Philippe Peyrat, Vennin, Philippe, Ferrer, Sandra Fert, Marie-Agnès Collonge-Rame, Mortemousque, Isabelle, McGuffog, Lesley, Chenevix-Trench, Georgia, Pereira-Smith, Olivia M, Antoniou, Antonis C, Cerón, Julián, Tominaga, Kaoru, Surrallés, Jordi, and Pujana, Miguel Angel
Subjects: ComputingMethodologies_PATTERNRECOGNITION, ComputerSystemsOrganization_COMPUTER-COMMUNICATIONNETWORKS, ComputingMethodologies_DOCUMENTANDTEXTPROCESSING, Hardware_INTEGRATEDCIRCUITS, Hardware_REGISTER-TRANSFER-LEVELIMPLEMENTATION
Abstract: Additional file 7: Co-AP and co-IP assays. Supplementary Figure 3 containing results of the co-AP and co-IP assays. (PDF 3 MB)
Published: 2020
Full Text: View/download PDF

6. Additional file 16 of Exploring the link between MORF4L1 and risk of breast cancer

Author: Martrat, Griselda, Maxwell, Christopher A, Tominaga, Emiko, Porta-De-La-Riva, Montserrat, Bonifaci, Núria, Gómez-Baldó, Laia, Bogliolo, Massimo, Conxi Lázaro, Blanco, Ignacio, Brunet, Joan, Aguilar, Helena, Fernández-Rodríguez, Juana, Seal, Sheila, Renwick, Anthony, Nazneen Rahman, Kühl, Julia, Neveling, Kornelia, Schindler, Detlev, Ramírez, María J, Castellà, María, Hernández, Gonzalo, Easton, Douglas F, Peock, Susan, Cook, Margaret, Oliver, Clare T, Frost, Debra, Platte, Radka, D Gareth Evans, Lalloo, Fiona, Eeles, Rosalind, Izatt, Louise, Chu, Carol, Davidson, Rosemarie, Kai-Ren Ong, Cook, Jackie, Douglas, Fiona, Hodgson, Shirley, Brewer, Carole, Morrison, Patrick J, Porteous, Mary, Peterlongo, Paolo, Manoukian, Siranoush, Peissel, Bernard, Zaffaroni, Daniela, Roversi, Gaia, Barile, Monica, Viel, Alessandra, Pasini, Barbara, Ottini, Laura, Putignano, Anna Laura, Savarese, Antonella, Bernard, Loris, Radice, Paolo, Healey, Sue, Spurdle, Amanda, Xiaoqing Chen, Beesley, Jonathan, Rookus, Matti A, Senno Verhoef, Tilanus-Linthorst, Madeleine A, Vreeswijk, Maaike P, Asperen, Christi J, Bodmer, Danielle, Ausems, Margreet GEM, Os, Theo A Van, Blok, Marinus J, Meijers-Heijboer, Hanne EJ, Hogervorst, Frans BL, Goldgar, David E, Buys, Saundra, John, Esther M, Miron, Alexander, Southey, Melissa, Daly, Mary B, Harbst, Katja, Borg, Åke, Rantala, Johanna, Barbany-Bustinza, Gisela, Ehrencrona, Hans, Stenmark-Askmalm, Marie, Kaufman, Bella, Laitman, Yael, Milgrom, Roni, Friedman, Eitan, Domchek, Susan M, Nathanson, Katherine L, Rebbeck, Timothy R, Johannsson, Oskar Thor, Couch, Fergus J, Xianshu Wang, Fredericksen, Zachary, Cuadras, Daniel, Moreno, Víctor, Pientka, Friederike K, Depping, Reinhard, Caldés, Trinidad, Osorio, Ana, Benítez, Javier, Bueren, Juan, Heikkinen, Tuomas, Nevanlinna, Heli, Hamann, Ute, Torres, Diana, Caligo, Maria Adelaide, Godwin, Andrew K, Imyanitov, Evgeny N, Ramunas Janavicius, Sinilnikova, Olga M, Stoppa-Lyonnet, Dominique, Mazoyer, Sylvie, Verny-Pierre, Carole, Castera, Laurent, Pauw, Antoine De, Yves-Jean Bignon, Uhrhammer, Nancy, Jean-Philippe Peyrat, Vennin, Philippe, Ferrer, Sandra Fert, Marie-Agnès Collonge-Rame, Mortemousque, Isabelle, McGuffog, Lesley, Chenevix-Trench, Georgia, Pereira-Smith, Olivia M, Antoniou, Antonis C, Cerón, Julián, Tominaga, Kaoru, Surrallés, Jordi, and Pujana, Miguel Angel
Subjects: Data_FILES
Abstract: Authors’ original file for figure 2
Published: 2020
Full Text: View/download PDF

7. Additional file 5 of Exploring the link between MORF4L1 and risk of breast cancer

Author: Martrat, Griselda, Maxwell, Christopher A, Tominaga, Emiko, Porta-De-La-Riva, Montserrat, Bonifaci, Núria, Gómez-Baldó, Laia, Bogliolo, Massimo, Conxi Lázaro, Blanco, Ignacio, Brunet, Joan, Aguilar, Helena, Fernández-Rodríguez, Juana, Seal, Sheila, Renwick, Anthony, Nazneen Rahman, Kühl, Julia, Neveling, Kornelia, Schindler, Detlev, Ramírez, María J, Castellà, María, Hernández, Gonzalo, Easton, Douglas F, Peock, Susan, Cook, Margaret, Oliver, Clare T, Frost, Debra, Platte, Radka, D Gareth Evans, Lalloo, Fiona, Eeles, Rosalind, Izatt, Louise, Chu, Carol, Davidson, Rosemarie, Kai-Ren Ong, Cook, Jackie, Douglas, Fiona, Hodgson, Shirley, Brewer, Carole, Morrison, Patrick J, Porteous, Mary, Peterlongo, Paolo, Manoukian, Siranoush, Peissel, Bernard, Zaffaroni, Daniela, Roversi, Gaia, Barile, Monica, Viel, Alessandra, Pasini, Barbara, Ottini, Laura, Putignano, Anna Laura, Savarese, Antonella, Bernard, Loris, Radice, Paolo, Healey, Sue, Spurdle, Amanda, Xiaoqing Chen, Beesley, Jonathan, Rookus, Matti A, Senno Verhoef, Tilanus-Linthorst, Madeleine A, Vreeswijk, Maaike P, Asperen, Christi J, Bodmer, Danielle, Ausems, Margreet GEM, Os, Theo A Van, Blok, Marinus J, Meijers-Heijboer, Hanne EJ, Hogervorst, Frans BL, Goldgar, David E, Buys, Saundra, John, Esther M, Miron, Alexander, Southey, Melissa, Daly, Mary B, Harbst, Katja, Borg, Åke, Rantala, Johanna, Barbany-Bustinza, Gisela, Ehrencrona, Hans, Stenmark-Askmalm, Marie, Kaufman, Bella, Laitman, Yael, Milgrom, Roni, Friedman, Eitan, Domchek, Susan M, Nathanson, Katherine L, Rebbeck, Timothy R, Johannsson, Oskar Thor, Couch, Fergus J, Xianshu Wang, Fredericksen, Zachary, Cuadras, Daniel, Moreno, Víctor, Pientka, Friederike K, Depping, Reinhard, Caldés, Trinidad, Osorio, Ana, Benítez, Javier, Bueren, Juan, Heikkinen, Tuomas, Nevanlinna, Heli, Hamann, Ute, Torres, Diana, Caligo, Maria Adelaide, Godwin, Andrew K, Imyanitov, Evgeny N, Ramunas Janavicius, Sinilnikova, Olga M, Stoppa-Lyonnet, Dominique, Mazoyer, Sylvie, Verny-Pierre, Carole, Castera, Laurent, Pauw, Antoine De, Yves-Jean Bignon, Uhrhammer, Nancy, Jean-Philippe Peyrat, Vennin, Philippe, Ferrer, Sandra Fert, Marie-Agnès Collonge-Rame, Mortemousque, Isabelle, McGuffog, Lesley, Chenevix-Trench, Georgia, Pereira-Smith, Olivia M, Antoniou, Antonis C, Cerón, Julián, Tominaga, Kaoru, Surrallés, Jordi, and Pujana, Miguel Angel
Subjects: fungi
Abstract: Additional file 5: Gene co-expression. Supplementary Figure 1 containing results of the gene co-expression analysis. (PDF 638 KB)
Published: 2020
Full Text: View/download PDF

8. Additional file 9 of Exploring the link between MORF4L1 and risk of breast cancer

Author: Martrat, Griselda, Maxwell, Christopher A, Tominaga, Emiko, Porta-De-La-Riva, Montserrat, Bonifaci, Núria, Gómez-Baldó, Laia, Bogliolo, Massimo, Conxi Lázaro, Blanco, Ignacio, Brunet, Joan, Aguilar, Helena, Fernández-Rodríguez, Juana, Seal, Sheila, Renwick, Anthony, Nazneen Rahman, Kühl, Julia, Neveling, Kornelia, Schindler, Detlev, Ramírez, María J, Castellà, María, Hernández, Gonzalo, Easton, Douglas F, Peock, Susan, Cook, Margaret, Oliver, Clare T, Frost, Debra, Platte, Radka, D Gareth Evans, Lalloo, Fiona, Eeles, Rosalind, Izatt, Louise, Chu, Carol, Davidson, Rosemarie, Kai-Ren Ong, Cook, Jackie, Douglas, Fiona, Hodgson, Shirley, Brewer, Carole, Morrison, Patrick J, Porteous, Mary, Peterlongo, Paolo, Manoukian, Siranoush, Peissel, Bernard, Zaffaroni, Daniela, Roversi, Gaia, Barile, Monica, Viel, Alessandra, Pasini, Barbara, Ottini, Laura, Putignano, Anna Laura, Savarese, Antonella, Bernard, Loris, Radice, Paolo, Healey, Sue, Spurdle, Amanda, Xiaoqing Chen, Beesley, Jonathan, Rookus, Matti A, Senno Verhoef, Tilanus-Linthorst, Madeleine A, Vreeswijk, Maaike P, Asperen, Christi J, Bodmer, Danielle, Ausems, Margreet GEM, Os, Theo A Van, Blok, Marinus J, Meijers-Heijboer, Hanne EJ, Hogervorst, Frans BL, Goldgar, David E, Buys, Saundra, John, Esther M, Miron, Alexander, Southey, Melissa, Daly, Mary B, Harbst, Katja, Borg, Åke, Rantala, Johanna, Barbany-Bustinza, Gisela, Ehrencrona, Hans, Stenmark-Askmalm, Marie, Kaufman, Bella, Laitman, Yael, Milgrom, Roni, Friedman, Eitan, Domchek, Susan M, Nathanson, Katherine L, Rebbeck, Timothy R, Johannsson, Oskar Thor, Couch, Fergus J, Xianshu Wang, Fredericksen, Zachary, Cuadras, Daniel, Moreno, Víctor, Pientka, Friederike K, Depping, Reinhard, Caldés, Trinidad, Osorio, Ana, Benítez, Javier, Bueren, Juan, Heikkinen, Tuomas, Nevanlinna, Heli, Hamann, Ute, Torres, Diana, Caligo, Maria Adelaide, Godwin, Andrew K, Imyanitov, Evgeny N, Ramunas Janavicius, Sinilnikova, Olga M, Stoppa-Lyonnet, Dominique, Mazoyer, Sylvie, Verny-Pierre, Carole, Castera, Laurent, Pauw, Antoine De, Yves-Jean Bignon, Uhrhammer, Nancy, Jean-Philippe Peyrat, Vennin, Philippe, Ferrer, Sandra Fert, Marie-Agnès Collonge-Rame, Mortemousque, Isabelle, McGuffog, Lesley, Chenevix-Trench, Georgia, Pereira-Smith, Olivia M, Antoniou, Antonis C, Cerón, Julián, Tominaga, Kaoru, Surrallés, Jordi, and Pujana, Miguel Angel
Subjects: congenital, hereditary, and neonatal diseases and abnormalities, hemic and lymphatic diseases, nutritional and metabolic diseases
Abstract: Additional file 9: siRNA-mediated depletion of MRG15 and FANCD2 monoubiquitinylation. Supplementary Figure 5 containing results of siRNA-mediated depletion of MRG15 and FANCD2 monoubiquitinylation. (PDF 1 MB)
Published: 2020
Full Text: View/download PDF

9. Additional file of Exploring the link between MORF4L1 and risk of breast cancer

Author: Martrat, Griselda, Maxwell, Christopher A, Tominaga, Emiko, Porta-De-La-Riva, Montserrat, Bonifaci, Núria, Gómez-Baldó, Laia, Bogliolo, Massimo, Conxi Lázaro, Blanco, Ignacio, Brunet, Joan, Aguilar, Helena, Fernández-Rodríguez, Juana, Seal, Sheila, Renwick, Anthony, Nazneen Rahman, Kühl, Julia, Neveling, Kornelia, Schindler, Detlev, Ramírez, María J, Castellà, María, Hernández, Gonzalo, Easton, Douglas F, Peock, Susan, Cook, Margaret, Oliver, Clare T, Frost, Debra, Platte, Radka, D Gareth Evans, Lalloo, Fiona, Eeles, Rosalind, Izatt, Louise, Chu, Carol, Davidson, Rosemarie, Kai-Ren Ong, Cook, Jackie, Douglas, Fiona, Hodgson, Shirley, Brewer, Carole, Morrison, Patrick J, Porteous, Mary, Peterlongo, Paolo, Manoukian, Siranoush, Peissel, Bernard, Zaffaroni, Daniela, Roversi, Gaia, Barile, Monica, Viel, Alessandra, Pasini, Barbara, Ottini, Laura, Putignano, Anna Laura, Savarese, Antonella, Bernard, Loris, Radice, Paolo, Healey, Sue, Spurdle, Amanda, Xiaoqing Chen, Beesley, Jonathan, Rookus, Matti A, Senno Verhoef, Tilanus-Linthorst, Madeleine A, Vreeswijk, Maaike P, Asperen, Christi J, Bodmer, Danielle, Ausems, Margreet GEM, Os, Theo A Van, Blok, Marinus J, Meijers-Heijboer, Hanne EJ, Hogervorst, Frans BL, Goldgar, David E, Buys, Saundra, John, Esther M, Miron, Alexander, Southey, Melissa, Daly, Mary B, Harbst, Katja, Borg, Åke, Rantala, Johanna, Barbany-Bustinza, Gisela, Ehrencrona, Hans, Stenmark-Askmalm, Marie, Kaufman, Bella, Laitman, Yael, Milgrom, Roni, Friedman, Eitan, Domchek, Susan M, Nathanson, Katherine L, Rebbeck, Timothy R, Johannsson, Oskar Thor, Couch, Fergus J, Xianshu Wang, Fredericksen, Zachary, Cuadras, Daniel, Moreno, Víctor, Pientka, Friederike K, Depping, Reinhard, Caldés, Trinidad, Osorio, Ana, Benítez, Javier, Bueren, Juan, Heikkinen, Tuomas, Nevanlinna, Heli, Hamann, Ute, Torres, Diana, Caligo, Maria Adelaide, Godwin, Andrew K, Imyanitov, Evgeny N, Ramunas Janavicius, Sinilnikova, Olga M, Stoppa-Lyonnet, Dominique, Mazoyer, Sylvie, Verny-Pierre, Carole, Castera, Laurent, Pauw, Antoine De, Yves-Jean Bignon, Uhrhammer, Nancy, Jean-Philippe Peyrat, Vennin, Philippe, Ferrer, Sandra Fert, Marie-Agnès Collonge-Rame, Mortemousque, Isabelle, McGuffog, Lesley, Chenevix-Trench, Georgia, Pereira-Smith, Olivia M, Antoniou, Antonis C, Cerón, Julián, Tominaga, Kaoru, Surrallés, Jordi, and Pujana, Miguel Angel
Subjects: skin and connective tissue diseases
Abstract: Additional file of Exploring the link between MORF4L1 and risk of breast cancer
Published: 2020
Full Text: View/download PDF

10. Rapid genetic counseling and testing in newly diagnosed breast cancer: Patients’ and health professionals’ attitudes, experiences, and evaluation of effects on treatment decision making

Author: Marianne A. Kuenen, Senno Verhoef, Marnix A. de Roos, Eveline M. A. Bleiker, Herman Rijna, Bart van Ooijen, Eline Vriens, Bart C. Vrouenraets, Thijs van Dalen, Jacoline van der Sanden-Melis, Emiel J. Th. Rutgers, Paul J Borgstein, Johannes P. Vente, Marijke R. Wevers, Arjen J. Witkamp, Wim H. Bouma, Margreet G. E. M. Ausems, Daniela E E Hahn, Titia Brouwer, Neil K. Aaronson, E. B. M. Theunissen, and Psychology Other Research (FMG)
Subjects: Adult, Male, medicine.medical_specialty, Referral, Attitude of Health Personnel, Genetic counseling, Decision Making, Breast Neoplasms, Genetic Counseling, Newly diagnosed, law.invention, 03 medical and health sciences, 0302 clinical medicine, Breast cancer, Randomized controlled trial, law, Humans, Medicine, Genetic Testing, 030212 general & internal medicine, Referral and Consultation, Aged, Health professionals, business.industry, General Medicine, Middle Aged, medicine.disease, Oncology, 030220 oncology & carcinogenesis, Family medicine, Usual care, Female, Surgery, Treatment decision making, business
Abstract: BACKGROUND: Rapid genetic counseling and testing (RGCT) in newly diagnosed high-risk breast cancer (BC) patients may influence surgical treatment decisions. To successfully integrate RGCT in practice, knowledge of professionals', and patients' attitudes toward RGCT is essential.METHODS: Between 2008 and 2010, we performed a randomized clinical trial evaluating the impact of RGCT. Attitudes toward and experience with RGCT were assessed in 265 patients (at diagnosis, 6- and 12-month follow-up) and 29 medical professionals (before and after the recruitment period).RESULTS: At 6-month follow-up, more patients who had been offered RGCT felt they had been actively involved in treatment decision-making than patients who had been offered usual care (67% vs 48%, P = 0.06). Patients who received DNA-test results before primary surgery reported more often that RGCT influenced treatment decisions than those who received results afterwards (P CONCLUSIONS: RGCT is viewed as helpful for newly diagnosed high-risk BC patients in choosing their primary surgery and should be offered routinely by surgeons.
Published: 2017
Full Text: View/download PDF

11. Three-step site-directed mutagenesis screen identifies pathogenic

Author: Hellen, Houlleberghs, Marleen, Dekker, Jarnick, Lusseveld, Wietske, Pieters, Thomas, van Ravesteyn, Senno, Verhoef, Robert M W, Hofstra, and Hein, Te Riele
Subjects: Mutation, Missense, Genetic Variation, Mouse Embryonic Stem Cells, Colorectal Neoplasms, Hereditary Nonpolyposis, Disease Models, Animal, Mice, Codon, Nonsense, Mutagenesis, Site-Directed, Animals, Humans, Genetic Predisposition to Disease, Genetic Testing, Frameshift Mutation, MutL Protein Homolog 1
Abstract: Inactivating mutations in the MLH1 DNA mismatch repair (MMR) gene underlie 42% of Lynch syndrome (LS) cases. LS is a cancer predisposition causing early onset colorectal and endometrial cancer. Nonsense and frameshift alterations unambiguously cause LS. The phenotype of missense mutations that only alter a single amino acid is often unclear. These variants of uncertain significance (VUS) hinder LS diagnosis and family screening and therefore functional tests are urgently needed. We developed a functional test for MLH1 VUS termed 'oligonucleotide-directed mutation screening' (ODMS).TheIn a proof-of-principle analysis, we demonstrate that ODMS can distinguish pathogenic and non-pathogenicODMS is a reliable tool to identify pathogenic
Published: 2019

12. Association of genetic susceptibility variants for type 2 diabetes with breast cancer risk in women of European ancestry

Author: Javier Benitez, Alicia Beeghly-Fadiel, Roger L. Milne, Graham G. Giles, Florentia Fostira, Senno Verhoef, Qin Wang, Simon S. Cross, Jenny Chang-Claude, Jacques Simard, Vessela N. Kristensen, Hoda Anton-Culver, Kathleen E. Malone, Veli-Matti Kosma, Pascal Guénel, Esther M. John, Stig E. Bojesen, Jan Lubinski, Patricia Harrington, Giske Ursin, Muhammad G. Kibriya, Artitaya Lophatananon, Mieke Kriege, Fergus J. Couch, Maria Kabisch, Judith S. Brand, Ute Hamann, Henrik Flyger, Susan L. Neuhausen, Elinor J. Sawyer, Mikael Hartman, Robert Luben, Thilo Dörk, Wanqing Wen, Hiltrud Brauch, Marilie D. Gammon, Xiao-Ou Shu, Ben Shan Zhang, Minouk J. Schoemaker, M. Pilar Zamora, Jirong Long, Rita K. Schmutzler, Natalia Bogdanova, Sofia Khan, Siranoush Manoukian, Anne Lise Børresen-Dale, Barbara Burwinkel, Regina M. Santella, Ian Tomlinson, Manjeet K. Bolla, Shan Wang-Gohrke, Nichola Johnson, Thérèse Truong, Rob B. van der Luijt, Amanda E. Toland, Carl Blomqvist, Catriona McLean, Georgia Chenevix-Trench, Anthony J. Swerdlow, Jingmei Li, Habibul Ahsan, David J. Hunter, Kristiina Aittomäki, Hui Zhao, Hui Miao, Wei Zheng, Olivia Fletcher, Alison M. Dunning, Marjanka K. Schmidt, Kenneth Muir, Per Hall, Farzana Jasmine, Eunjung Lee, Melissa C. Southey, Robert Winqvist, Janet E. Olson, Anna Jakubowska, Paul D.P. Pharoah, Martine Dumont, Dieter Flesch-Janys, Barbara Perkins, Douglas F. Easton, Christopher A. Haiman, Jonine D. Figueroa, Julia A. Knight, Kamila Czene, Loic Le Marchand, Katri Pylkäs, Angela Cox, Maartje J. Hooning, Kyriaki Michailidou, John L. Hopper, Qiuyin Cai, Volker Arndt, Heli Nevanlinna, Sara Lindström, Hanne Meijers-Heijboer, Sara Margolin, Zhiguo Zhao, Mitul Shah, Matthias W. Beckmann, Alfons Meindl, Martha J. Shrubsole, Paolo Peterlongo, Frederik Marmé, Peter Kraft, Irene L. Andrulis, Annika Lindblom, Diana Torres, Anja Rudolph, Arto Mannermaa, Graham Casey, Alice S. Whittemore, Hermann Brenner, Patrick Neven, Kelly-Anne Phillips, Peter A. Fasching, Montserrat Garcia-Closas, Human genetics, CCA - Cancer biology, Wang, Jean [0000-0002-9139-0627], Luben, Robert [0000-0002-5088-6343], Dunning, Alison [0000-0001-6651-7166], Pharoah, Paul [0000-0001-8494-732X], Easton, Douglas [0000-0003-2444-3247], Apollo - University of Cambridge Repository, and Medical Oncology
Subjects: 0301 basic medicine, Oncology, Cancer Research, endocrine system diseases, Epidemiology, Genome-wide association study, Type 2 diabetes, Breast cancer, 0302 clinical medicine, Risk Factors, Ethnicity, Odds Ratio, GWAS, Non-U.S. Gov't, Research Support, Non-U.S. Gov't, Middle Aged, 3. Good health, 030220 oncology & carcinogenesis, Public Health and Health Services, Female, medicine.medical_specialty, Oncology and Carcinogenesis, European Continental Ancestry Group, Non-P.H.S, Ethnic Groups, Breast Neoplasms, Research Support, Polymorphism, Single Nucleotide, Article, White People, N.I.H, 03 medical and health sciences, Research Support, N.I.H., Extramural, SDG 3 - Good Health and Well-being, Internal medicine, Genetic susceptibility, Journal Article, medicine, Genetic predisposition, Humans, Genetic Predisposition to Disease, business.industry, Case-control study, Genetic Variation, Extramural, nutritional and metabolic diseases, Cancer, Odds ratio, medicine.disease, Obesity, 030104 developmental biology, Diabetes Mellitus, Type 2, Case-Control Studies, U.S. Gov't, business, Research Support, U.S. Gov't, Non-P.H.S, Demography
Abstract: Purpose: Type 2 diabetes (T2D) has been reported to be associated with an elevated risk of breast cancer. It is unclear, however, whether this association is due to shared genetic factors.\ud Methods: We constructed a genetic risk score (GRS) using risk variants from 33 known independent T2D susceptibility loci and evaluated its relation to breast cancer risk using the data from two consortia, including 62,328 breast cancer patients and 83,817 controls of European ancestry. Unconditional logistic regression models were used to derive adjusted odds ratios (ORs) and 95 % confidence intervals (CIs) to measure the association of breast cancer risk with T2D GRS or T2D-associated genetic risk variants. Meta-analyses were conducted to obtain summary ORs across all studies.\ud Results: The T2D GRS was not found to be associated with breast cancer risk, overall, by menopausal status, or for estrogen receptor positive or negative breast cancer. Three T2D associated risk variants were individually associated with breast cancer risk after adjustment for multiple comparisons using the Bonferroni method (at p < 0.001), rs9939609 (FTO) (OR 0.94, 95 % CI = 0.92–0.95, p = 4.13E−13), rs7903146 (TCF7L2) (OR 1.04, 95 % CI = 1.02–1.06, p = 1.26E−05), and rs8042680 (PRC1) (OR 0.97, 95 % CI = 0.95–0.99, p = 8.05E−04).\ud Conclusions: We have shown that several genetic risk variants were associated with the risk of both T2D and breast cancer. However, overall genetic susceptibility to T2D may not be related to breast cancer risk.
Published: 2016
Full Text: View/download PDF

13. Oligonucleotide-directed mutagenesis screen to identify pathogenic Lynch syndrome-associated MSH2 DNA mismatch repair gene variants

Author: Hendrikus J. Dubbink, Hellen Houlleberghs, Marleen Dekker, Senno Verhoef, Robert M.W. Hofstra, Roos Kleinendorst, Hildo Lantermans, Hein te Riele, Pathology, Clinical Genetics, Human genetics, and CCA - Cancer biology
Subjects: 0301 basic medicine, Genetics, congenital, hereditary, and neonatal diseases and abnormalities, Mutation, Multidisciplinary, Guanine analog, Biological Sciences, Biology, medicine.disease_cause, medicine.disease, digestive system diseases, Lynch syndrome, 03 medical and health sciences, 030104 developmental biology, SDG 3 - Good Health and Well-being, MSH2, medicine, Missense mutation, DNA mismatch repair, Gene, Genetic screen
Abstract: Single-stranded DNA oligonucleotides can achieve targeted base-pair substitution with modest efficiency but high precision. We show that "oligo targeting" can be used effectively to study missense mutations in DNA mismatch repair (MMR) genes. Inherited inactivating mutations in DNA MMR genes are causative for the cancer predisposition Lynch syndrome (LS). Although overtly deleterious mutations in MMR genes can clearly be ascribed as the cause of LS, the functional implications of missense mutations are often unclear. We developed a genetic screen to determine the pathogenicity of these variants of uncertain significance (VUS), focusing on mutator S homolog 2 (MSH2). VUS were introduced into the endogenous Msh2 gene of mouse embryonic stem cells by oligo targeting. Subsequent selection for MMR-deficient cells using the guanine analog 6-thioguanine allowed the detection of MMR-abrogating VUS. The screen was able to distinguish weak and strong pathogenic variants from polymorphisms and was used to investigate 59 Msh2 VUS. Nineteen of the 59 VUS were identified as pathogenic. Functional assays revealed that 14 of the 19 detected variants fully abrogated MMR activity and that five of the detected variants attenuated MMR activity. Implementation of the screen in clinical practice allows proper counseling of mutation carriers and treatment of their tumors.
Published: 2016
Full Text: View/download PDF

14. Does rapid genetic counseling and testing in newly diagnosed breast cancer patients cause additional psychosocial distress? Results from a randomized clinical trial

Author: Rob B. van der Luijt, Thijs van Dalen, Senno Verhoef, Bart van Ooijen, Neil K. Aaronson, Heiddis Valdimarsdottir, Marijke R. Wevers, Frans B. L. Hogervorst, Arjen J. Witkamp, B. C. Vrouenraets, Paul J Borgstein, Wim H. Bouma, Eveline M. A. Bleiker, Eline Vriens, Herman Rijna, Margreet G. E. M. Ausems, Marnix A. de Roos, E. B. M. Theunissen, Jacobien M. Kieffer, Emiel J. Th. Rutgers, Daniela E E Hahn, Titia Brouwer, Johannes P. Vente, and Klinische Psychologie (Psychologie, FMG)
Subjects: Adult, medicine.medical_specialty, Pediatrics, Time Factors, Genetic counseling, Genes, BRCA2, Genes, BRCA1, Breast Neoplasms, Genetic Counseling, Newly diagnosed, Research Support, law.invention, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Breast cancer, breast cancer, Randomized controlled trial, Quality of life, law, BRCA1/2, medicine, Journal Article, Humans, Genetics(clinical), Genetic Testing, 030212 general & internal medicine, Non-U.S. Gov't, Genetics (clinical), Aged, business.industry, Research Support, Non-U.S. Gov't, psychosocial distress, Middle Aged, medicine.disease, Distress, genetic counseling and testing, quality of life, 030220 oncology & carcinogenesis, Randomized Controlled Trial, Physical therapy, Female, business, Psychosocial
Abstract: Purpose: Female breast cancer patients carrying a BRCA1/2 mutation have an increased risk of second primary breast cancer. Rapid genetic counseling and testing (RGCT) before surgery may influence choice of primary surgical treatment. In this article, we report on the psychosocial impact of RGCT.Methods: Newly diagnosed breast cancer patients at risk for carrying a BRCA1/2 mutation were randomized to an intervention group (offer of RGCT) or a usual care control group (ratio 2:1). Psychosocial impact and quality of life were assessed with the Impact of Events Scale, Hospital Anxiety and Depression Scale, Cancer Worry Scale, and the EORTC QLQ-C30 and QLQ-BR23. Assessments took place at study entry and at 6- and 12-month follow-up visits.Results: Between 2008 and 2010, 265 patients were recruited into the study. Completeness of follow-up data was more than 90%. Of the 178 women in the intervention group, 177 had genetic counseling, of whom 71 (40%) had rapid DNA testing and 59 (33%) received test results before surgery. Intention-to-treat and per-protocol analyses showed no statistically significant differences between groups over time in any of the psychosocial outcomes.Conclusions: In this study, RGCT in newly diagnosed breast cancer patients did not have any measurable adverse psychosocial effects.
Published: 2016
Full Text: View/download PDF

15. Association of Type and Location of BRCA1 and BRCA2 Mutations With Risk of Breast and Ovarian Cancer

Author: Caroline Seynaeve, Katja Harbst, Eric A. Ross, Nandita Mitra, Elisa Alducci, Marco Montagna, Janusz Menkiszak, Marion Gauthier-Villars, Javier Benitez, Carole Brewer, Etienne Rouleau, Inge Søkilde Pedersen, Orland Diez, Anya Kushnir, Antonis C. Antoniou, Christine Rappaport, Florentia Fostira, Maurizio Genuardi, Simona Agata, Mark H. Greene, Mary Beth Terry, Nicola Dikow, David E. Goldgar, Anna Jakubowska, Min Hyuk Lee, Sylvie Mazoyer, Diana Eccles, Shirley Hodgson, Anne-Marie Gerdes, Alexander Miron, Laima Tihomirova, Alan Donaldson, Adalgeir Arason, Rosalind A. Eeles, Fergus J. Couch, Hans Jörg Plendl, Francesca Vignolo-Lutati, Ute Hamann, Jackie Cook, Torben A Kruse, Shani Paluch-Shimon, Lisa Walker, Doris Steinemann, Dorothea Gadzicki, Juul T. Wijnen, Markus C. Fleisch, Kenneth Offit, Mary B. Daly, Jamal Zidan, Georgia Chenevix-Trench, Stephanie V. Blank, Marc Tischkowitz, Esther Darder, Annette Fontaine, Louise Izatt, Elżbieta Złowocka-Perłowska, Nadia Boutry-Kryza, Frans B. L. Hogervorst, Stefanie Engert, Danièle Muller, Susan M. Domchek, Phuong L. Mai, Senno Verhoef, Bernhard H. F. Weber, Cecilia M. Dorfling, Kathleen Claes, Kristiina Aittomäki, Annemarie H. van der Hout, Sharon Sand, Olufunmilayo I. Olopade, Margreet G. E. M. Ausems, Aleksandra Tołoczko-Grabarek, Trevor Cole, Giulietta Scuvera, Ana Osorio, Niklas Loman, Timothy R. Rebbeck, Riccardo Dolcetti, Marit Beer, Harsh B. Pathak, Douglas F. Easton, Lone Sunde, Conxi Lázaro, Raanan Berger, Paolo Radice, Mads Thomassen, Ignacio Blanco, Joseph Vijai, Kristie Bobolis, János Papp, Jean-Pierre Fricker, Christine Walsh, Patricia A. Ganz, Marie Stenmark-Askmalm, Andrea Gehrig, Vernon S. Pankratz, Atocha Romero, Xianshu Wang, Loris Bernard, Viviana Gismondi, Mary Porteous, Muy-Kheng Tea, Karen H. Lu, Gustavo C. Rodriguez, Bernardo Bonanni, Christoph Mundhenke, Julian Adlard, Bent Ejlertsen, Dominique Stoppa-Lyonnet, Nadine Tung, Patrick J. Morrison, Dezheng Huo, Cezary Cybulski, Jack Basil, Georg Pfeiler, Daphne Gschwantler-Kaulich, Heli Nevanlinna, Anders Bojesen, Marion Piedmonte, Katherine L. Nathanson, Amanda E. Toland, Sung-Won Kim, Judy Garber, Amanda B. Spurdle, Noralane M. Lindor, Sanne Traasdahl Moeller, Hans Ehrencrona, Trinidad Caldés, Rosemarie Davidson, Karin Kast, Jenny Lester, Shan Wang-Gohrke, Norbert Arnold, Ana Peixoto, Christine Lasset, Andreas Berger, Olga M. Sinilnikova, Katie Wakely, Claude Houdayer, Mercedes Durán, Robert L. Nussbaum, Ramūnas Janavičius, Christina G. Selkirk, Paolo Aretini, Nina Ditsch, J. Margriet Collée, Rosa B. Barkardottir, Sue Healey, Tomasz Huzarski, Cora M. Aalfs, Gillian Mitchell, Peter J. Hulick, Encarna B. Gomez Garcia, Zakaria Einbeigi, Christian F. Singer, Leigha Senter, Yuan Chun Ding, Dieter Niederacher, Yael Laitman, Siranoush Manoukian, Christoph Engel, Anne De Paepe, Anneliese Fink-Retter, Irene L. Andrulis, Rachel Laframboise, Maria A. Caligo, Priyanka Sharma, Miguel de la Hoya, Teresa Ramón y Cajal, Bruce Poppe, Thomas Hansen, Francesca Damiola, Anne-Bine Skytte, Susan L. Neuhausen, Christian Sutter, Marie-Agnès Collonge-Rame, Johannes J. P. Gille, Barbara Pasini, Wendy K. Chung, Noah D. Kauff, M. John Kennedy, Diana Torres, Salina B. Chan, Mark E. Robson, Elizabeth J. van Rensburg, Eric Hahnen, Barbara Wappenschmidt, Grzegorz Sukiennicki, Esther M. John, Rohini Rau-Murthy, Alice S. Whittemore, Kunle Odunsi, Masoud Azodi, John F. Boggess, Sue K. Park, Rita K. Schmutzler, Muriel Belotti, Jeffrey N. Weitzel, Simon A. Gayther, Fei Wan, Andrew K. Godwin, Arjen R. Mensenkamp, Daniela Zaffaroni, Jacques Simard, Susan Peock, Soo Hwang Teo, Claus R. Bartram, Evgeny N. Imyanitov, Maria-Isabel Tejada, Giuseppe Giannini, Mónica Salinas, Banu Arun, Jan C. Oosterwijk, Jacek Gronwald, Alexandra Becker, Tara M. Friebel, Lenka Foretova, Catherine Noguès, Muhammad Usman Rashid, Valeria Pensotti, Antonella Savarese, Debra Frost, Beatrice Melin, Drakoulis Yannoukakos, Steve Ellis, Jean-Philippe Peyrat, Hagay Sobol, Kim De Leeneer, Radka Platte, Jan Lubinski, Javier Godino, Lesley McGuffog, Tomasz Byrski, Claudine Isaacs, Johanna Rantala, Kelly-Anne Phillips, Carolien M. Kets, Uffe Birk Jensen, Katarzyna Durda, Linda Steele, Beth Y. Karlan, Ava Kwong, Alfons Meindl, Lucia Guidugli, Raymonda Varon-Mateeva, D. Gareth Evans, Edith Olah, Isabelle Mortemousque, Manuel R. Teixeira, Joyce Seldon, Katarzyna Jaworska-Bieniek, Bernard Peissel, Saundra S. Buys, Peter Devilee, Kerstin Rhiem, Eitan Friedman, RS: GROW - Oncology, RS: GROW - R4 - Reproductive and Perinatal Medicine, Damage and Repair in Cancer Development and Cancer Treatment (DARE), Targeted Gynaecologic Oncology (TARGON), Cancer Research UK, National Institutes of Health (US), University of Pennsylvania, Breast Cancer Research Foundation, Human Genetics, Human genetics, and Epidemiology and Data Science
Subjects: endocrine system diseases, Genes, BRCA2, MathematicsofComputing_GENERAL, Genes, BRCA1, cancer risk, Settore MED/03 - GENETICA MEDICA, medicine.disease_cause, MOUSE MODELS, Risk Factors, Tumours of the digestive tract Radboud Institute for Molecular Life Sciences [Radboudumc 14], Age of Onset, POSITION, skin and connective tissue diseases, Adult, Breast Neoplasms, Female, Heterozygote, Humans, Middle Aged, Nucleotides, Ovarian Neoplasms, Genetic Predisposition to Disease, Mutation, Medicine (all), MESSENGER-RNA DECAY, UNKNOWN CLINICAL-SIGNIFICANCE, BRCA1 and BRCA2 genes, mutation type and position, cancer risk, TheoryofComputation_GENERAL, General Medicine, GERMLINE MUTATIONS, CARRIERS, 3. Good health, SUSCEPTIBILITY GENE, Medical genetics, Rare cancers Radboud Institute for Health Sciences [Radboudumc 9], medicine.medical_specialty, PROTEINS, mutation type and position, BRCA1 and BRCA2 genes, DNA-SEQUENCE VARIANTS, Article, REGION, Breast cancer, Germline mutation, medicine, BRCA1 or BRCA2, business.industry, Cancer, Heterozygote advantage, medicine.disease, Cancer research, Age of onset, Ovarian cancer, business
Abstract: CIMBA Consortium et al., PMID: 25849179, [Importance]: Limited information about the relationship between specific mutations in BRCA1 or BRCA2 (BRCA1/2) and cancer risk exists. [Objective]: To identify mutation-specific cancer risks for carriers of BRCA1/2. [Design, Setting, and Participants]: Observational study ofwomen whowere ascertained between 1937 and 2011 (median, 1999) and found to carry disease-associated BRCA1 or BRCA2 mutations. The international sample comprised 19 581 carriers of BRCA1 mutations and 11 900 carriers of BRCA2 mutations from 55 centers in 33 countries on 6 continents.We estimated hazard ratios for breast and ovarian cancer based on mutation type, function, and nucleotide position.We also estimated RHR, the ratio of breast vs ovarian cancer hazard ratios. A value of RHR greater than 1 indicated elevated breast cancer risk; a value of RHR less than 1 indicated elevated ovarian cancer risk. [Exposures]: Mutations of BRCA1 or BRCA2. [Main Outcomes and Measures]: Breast and ovarian cancer risks. [Results]: Among BRCA1 mutation carriers, 9052 women (46%) were diagnosed with breast cancer, 2317 (12%) with ovarian cancer, 1041 (5%) with breast and ovarian cancer, and 7171 (37%) without cancer. Among BRCA2 mutation carriers, 6180 women (52%) were diagnosed with breast cancer, 682 (6%) with ovarian cancer, 272 (2%) with breast and ovarian cancer, and 4766 (40%) without cancer. In BRCA1, we identified 3 breast cancer cluster regions (BCCRs) located at c.179 to c.505 (BCCR1; RHR = 1.46; 95%CI, 1.22-1.74; P = 2 × 10-6), c.4328 to c.4945 (BCCR2; RHR = 1.34; 95%CI, 1.01-1.78; P = .04), and c. 5261 to c.5563 (BCCR2', RHR = 1.38; 95%CI, 1.22-1.55; P = 6 × 10-9).We also identified an ovarian cancer cluster region (OCCR) from c.1380 to c.4062 (approximately exon 11) with RHR = 0.62 (95%CI, 0.56-0.70; P = 9 × 10-17). In BRCA2, we observed multiple BCCRs spanning c.1 to c.596 (BCCR1; RHR = 1.71; 95%CI, 1.06-2.78; P = .03), c.772 to c.1806 (BCCR1'; RHR = 1.63; 95%CI, 1.10-2.40; P = .01), and c.7394 to c.8904 (BCCR2; RHR = 2.31; 95%CI, 1.69-3.16; P = .00002).We also identified 3 OCCRs: the first (OCCR1) spanned c.3249 to c.5681 that was adjacent to c.5946delT (6174delT; RHR = 0.51; 95%CI, 0.44-0.60; P = 6 × 10-17). The second OCCR spanned c.6645 to c.7471 (OCCR2; RHR = 0.57; 95%CI, 0.41-0.80; P = .001). Mutations conferring nonsense-mediated decay were associated with differential breast or ovarian cancer risks and an earlier age of breast cancer diagnosis for both BRCA1 and BRCA2 mutation carriers. [Conclusions and Relevance]: Breast and ovarian cancer risks varied by type and location of BRCA1/2 mutations. With appropriate validation, these data may have implications for risk assessment and cancer prevention decision making for carriers of BRCA1 and BRCA2 mutations., Dr Antoniou and the CIMBA data management are funded by Cancer Research UK. Dr Easton is a Principal Research Fellow of Cancer Research UK. Dr Rebbeck is supported by R01-CA083855, R01-CA102776, and P50-CA083638 from the National Institutes of Health (NIH). Dr Rebbeck, Dr Nathanson, Ms Friebel, and Dr Domchek are supported by the Basser Research Center at the University of Pennsylvania. Dr Nathanson is supported by the Breast Cancer Research Foundation. Drs Domchek and Nathanson are supported by the Rooney Family Foundation. Dr Poppe is supported by R01-CA112520 from NIH. Cancer Research UK provided financial support for this work. Dr Antoniou is a Senior Cancer Research UK Cancer Research Fellow. Dr Phillips is a National Breast Cancer Foundation (Australia) Practitioner Fellow.
Published: 2015
Full Text: View/download PDF

16. Genome-wide association analysis of more than 120,000 individuals identifies 15 new susceptibility loci for breast cancer

Author: Vesa Kataja, Aida Karina Dieffenbach, Chia-Ni Hsiung, Catherine S. Healey, Gie Hooi Tan, Soo Hwang Teo, Domenico Palli, Frederik Marme, Katri Pylkäs, Roger L. Milne, Jaana M. Hartikainen, Gord Glendon, Susan L. Slager, Chen-Yang Shen, Fredrick R. Schumacher, Daniel F. Schmidt, Suleeporn Sangrajrang, Kee Seng Chia, Lorna Gibson, Pascal Guénel, Alice S. Whittemore, Jenny Chang-Claude, Yu Tang Gao, Hidemi Ito, Simon S. Cross, Sofia Khan, Marie Sanchez, Daniel Vincent, Daniel Herrero, Nicola Miller, Antoinette Hollestelle, Caroline M. Seynaeve, Christopher A. Haiman, Hermann Brenner, Kay-Tee Khaw, Loris Bernard, Habibul Ahsan, Melissa C. Southey, David Van Den Berg, Martha J. Shrubsole, Daniel O. Stram, William Blot, Mel Maranian, Robert Winqvist, Keitaro Matsuo, John W. M. Martens, Heli Nevanlinna, Mia M. Gaudet, Anna Jakubowska, Christine D. Berg, Paul D.P. Pharoah, Jacques Simard, Manjeet K. Bolla, Dieter Flesch-Janys, Mark S. Goldberg, Paul Brennan, Ching Wan Chan, Sune F. Nielsen, Sara Lindström, Mitul Shah, Matthias W. Beckmann, Craig Luccarini, Jonathan Beesley, Kyriaki Michailidou, Paolo Peterlongo, Marc J. Gunter, Anna González-Neira, Ji Yeob Choi, Per Hall, Sarah Stewart-Brown, Keith Humphreys, Hui Cai, Kathleen E. Malone, Elinor J. Sawyer, Louise A. Brinton, Marjanka K. Schmidt, Xiao-Ou Shu, Barbara Perkins, Lotte Maxild Mortensen, Chiu-Chen Tseng, Hanne Meijers-Heijboer, Minouk J. Schoemaker, Keun-Young Yoo, Julia A. Knight, Alan Ashworth, Stig E. Bojesen, Kamila Czene, Artitaya Lophatananon, Graham G. Giles, S. Ahmed, Kazuo Tajima, Douglas F. Easton, Maria Kabisch, Arja Jukkola-Vuorinen, Wei Lu, Peter A. Fasching, Irene L. Andrulis, Clare Turnbull, Caroline Baynes, Christine B. Ambrosone, Jan Lubinski, Muriel A. Adank, A. Meindl, Taru A. Muranen, Siranoush Manoukian, Susan M. Gapstur, Natalia Bogdanova, Alexander Hein, Annika Lindblom, Nazneen Rahman, Annegien Broeks, Lothar Haeberle, Federico Canzian, G Pita, Ming-Feng Hou, Hiroji Iwata, Drakoulis Yannoukakos, Diana Torres, Vessela N. Kristensen, Peter Devilee, Qiuyin Cai, Christi J Asperen, John L. Hopper, Diether Lambrechts, Michael Lush, Hans Wildiers, Joe Dennis, Sandra L. Halverson, Carl Blomqvist, Erik Van Limbergen, Malin Sund, Daehee Kang, Grethe I. Grenaker Alnæs, Marilie D. Gammon, Ursula Eilber, Ian Tomlinson, Thérèse Truong, Amanda E. Toland, Anna Marie Mulligan, Kirsimari Aaltonen, Olivia Fletcher, Jonine D. Figueroa, Angela Cox, Pei Ei Wu, Maartje J. Hooning, Catriona McLean, Georgia Chenevix-Trench, Pornthep Siriwanarangsan, Malcolm W.R. Reed, Emily Hallberg, Sara Margolin, Volker Arndt, Montserrat Garcia-Closas, Francois Bacot, Rita K. Schmutzler, Julian Peto, David J. Hunter, Thomas Brüning, Katarzyna Jaworska, Christof Sohn, Børge G. Nordestgaard, Enes Makalic, Hatef Darabi, Barbara Burwinkel, Petra P.H. Peeters, J. Margriet Collée, Rongxi Yang, Robert N. Hoover, Eiliv Lund, Fergus J. Couch, Ute Hamann, Jirong Long, Wei Zheng, Sabine Behrens, Giske Ursin, Muhammad G. Kibriya, Claire Mulot, Laure Dossus, Helen Tsimiklis, Tomasz Huzarski, Peter Kraft, Anja Rudolph, Arto Mannermaa, Alison M. Dunning, Lisa B. Signorello, Valerie Gaborieau, Kenneth Muir, Anthony J. Swerdlow, Javier Benitez, Judith S. Brand, Sander Canisius, Hoda Anton-Culver, Veli-Matti Kosma, Thilo Dörk, Sten Cornelissen, Christa Stegmaier, Cheng Har Yip, Brian E. Henderson, Harald Surowy, Jingmei Li, Nur Aishah Taib, W. Ryan Diver, Carmel Apicella, Janet E. Olson, Kristiina Aittomäki, Celine M. Vachon, Regina M. Santella, Dimitrios Trichopoulos, Jianjun Liu, Nick Orr, Martine Dumont, Christian Sutter, Sue K. Park, Mikael Hartman, Susan L. Neuhausen, Hui Miao, M. Pilar Zamora, Anna H. Wu, Rob B. van der Luijt, Isabel dos-Santos-Silva, Graham Casey, Henrik Flyger, M. Rosario Alonso, Nuria Álvarez, Michael J. Kerin, Loic Le Marchand, Jose Ignacio Arias Perez, Mikael Eriksson, Esther M. John, Quinten Waisfisz, Qin Wang, Daniel C. Tessier, Paolo Radice, Robert A.E.M. Tollenaar, James McKay, Silje Nord, Hiltrud Brauch, José María Huerta, Stephen J. Chanock, Mervi Grip, Patrick Neven, Senno Verhoef, Clinical Genetics, Obstetrics & Gynecology, Medical Oncology, Cardiothoracic Surgery, Dennis, Joe [0000-0003-4591-1214], Wang, Jean [0000-0002-9139-0627], Khaw, Kay-Tee [0000-0002-8802-2903], Pharoah, Paul [0000-0001-8494-732X], Dunning, Alison [0000-0001-6651-7166], Easton, Douglas [0000-0003-2444-3247], Apollo - University of Cambridge Repository, Human genetics, and CCA - Oncogenesis
Subjects: Breast Neoplasms, Single-nucleotide polymorphism, Genome-wide association study, Biology, Research Support, Polymorphism, Single Nucleotide, N.I.H, Cohort Studies, brca1, Breast cancer, Research Support, N.I.H., Extramural, Meta-Analysis as Topic, SDG 3 - Good Health and Well-being, common variants, Journal Article, estrogen, chek2-asterisk-1100delc, Genetics, medicine, Humans, Genetic Predisposition to Disease, 1000 Genomes Project, Non-U.S. Gov't, genotype imputation, risk, Genetic association, Research Support, Non-U.S. Gov't, Chromatin binding, Extramural, Cancer, Microarray Analysis, confer susceptibility, medicine.disease, 3. Good health, ovarian-cancer, Genetic Loci, Case-Control Studies, alleles, Female, Imputation (genetics), Genome-Wide Association Study, metaanalysis
Abstract: Genome-wide association studies (GWAS) and large-scale replication studies have identified common variants in 79 loci associated with breast cancer, explaining ∼14% of the familial risk of the disease. To identify new susceptibility loci, we performed a meta-analysis of 11 GWAS, comprising 15,748 breast cancer cases and 18,084 controls together with 46,785 cases and 42,892 controls from 41 studies genotyped on a 211,155-marker custom array (iCOGS). Analyses were restricted to women of European ancestry. We generated genotypes for more than 11 million SNPs by imputation using the 1000 Genomes Project reference panel, and we identified 15 new loci associated with breast cancer at P < 5 × 10(-8). Combining association analysis with ChIP-seq chromatin binding data in mammary cell lines and ChIA-PET chromatin interaction data from ENCODE, we identified likely target genes in two regions: SETBP1 at 18q12.3 and RNF115 and PDZK1 at 1q21.1. One association appears to be driven by an amino acid substitution encoded in EXO1. ispartof: Nature Genetics vol:47 issue:4 pages:373-80 ispartof: location:United States status: published
Published: 2015
Full Text: View/download PDF

17. Familial versus Sporadic Breast Cancer: Different Treatments for Similar Tumors?

Author: Ellen G. Engelhardt, Mieke Kriege, Maartje J. Hooning, Caroline Seynaeve, Rob A. E. M. Tollenaar, Christina J. van Asperen, Margreet G. E. M. Ausems, Lonneke V. van de Poll-Franse, Stella Mook, Senno Verhoef, Matti A. Rookus, HEBON Collaborators, and Marjanka K. Schmidt
Subjects: Oncology, medicine.medical_specialty, education.field_of_study, endocrine system diseases, medicine.diagnostic_test, business.industry, medicine.medical_treatment, Population, medicine.disease, Logistic regression, Breast cancer, Internal medicine, medicine, Family history, skin and connective tissue diseases, Ovarian cancer, education, business, General Economics, Econometrics and Finance, Estrogen Receptor Status, Mastectomy, Genetic testing
Abstract: Objective: It is unclear if and to what extent family history of breast/ovarian cancer or BRCA1/2-mutation carriership influences breast cancer treatment strategy. We investigated whether treatment differed between patients from BRCA1/2 families and those unselected for family history. Methods: We included 478 BRCA1/2-related patients referred for genetic testing before or after diagnosis. Two references were used: 13,498 population-based and 6896 hospital-based patients. Surgical treatment and adjuvant chemotherapy use was analyzed using logistic regression models, stratified by tumor size, nodal status, age at and period of diagnosis, and estrogen receptor status (ER). Results: BRCA1/2 cases aged 35 - 52 years at diagnosis and/or with tumors BRCA1 and ER-negative BRCA1/2-cases irrespective of age and nodal status (OR 1.9 to 24.3). Conclusion: After 1995 treatment of BRCA1/2-associated patients consisted notably of more mastectomies and adjuvant chemotherapy than their population-based counterparts with the same tumor characteristics. There is a need to be aware of such differences in daily practice and interpretation of survival studies on BRCA1/2 mutation carriers.
Published: 2015
Full Text: View/download PDF

18. Colorectal cancer risk variants at 8q23.3 and 11q23.1 are associated with disease phenotype in APC mutation carriers

Author: Jeanine J. Houwing-Duistermaat, Rolf H. Sijmons, Cora M. Aalfs, Nicoline Hoogerbrugge, Marry H. Nieuwenhuis, E. B. Gomez Garcia, Carli M. J. Tops, T. van Wezel, Senno Verhoef, Zeinab Ghorbanoghli, Fred H. Menko, Frederik J. Hes, Tom G.W. Letteboer, Hans F. A. Vasen, Shantie Jagmohan-Changur, Anja Wagner, Juul T. Wijnen, Guided Treatment in Optimal Selected Cancer Patients (GUTS), Human Genetics, Clinical Genetics, Faculty of Medicine and Pharmacy, Clinical sciences, Faculty of Economic and Social Sciences and Solvay Business School, Faculty of Psychology and Educational Sciences, Promovendi NTM, RS: GROW - R4 - Reproductive and Perinatal Medicine, MUMC+: DA KG Polikliniek (9), and Klinische Genetica
Subjects: Male, 0301 basic medicine, Cancer Research, Genome-wide association study, 0302 clinical medicine, Gene Frequency, GENETIC-VARIANTS, Genotype, Tumours of the digestive tract Radboud Institute for Molecular Life Sciences [Radboudumc 14], Genetics(clinical), Cancer genetics, Genetics (clinical), Medicine(all), Genetics, Familial adenomatous polyposis, REFINEMENT, LYNCH SYNDROME, Adenomatous Polyposis Coli/genetics, Lynch syndrome, Adenomatous Polyposis Coli, Oncology, 030220 oncology & carcinogenesis, Original Article, Colorectal Neoplasms, Chromosomes, Human, Pair 8, Adenoma, Adult, SUSCEPTIBILITY LOCI, Adenomatous Polyposis Coli Protein, Single-nucleotide polymorphism, Genetic polymorphisms, Polymorphism, Single Nucleotide, 03 medical and health sciences, Germline mutation, SDG 3 - Good Health and Well-being, MODIFIER GENES, medicine, Journal Article, Humans, Genetic Predisposition to Disease, Adenomatous Polyposis Coli Protein/genetics, Allele, GENOME-WIDE ASSOCIATION, Allele frequency, business.industry, Chromosomes, Human, Pair 11, FAP, ALLELES, medicine.disease, Adenoma/genetics, Colorectal Neoplasms/genetics, digestive system diseases, 030104 developmental biology, SEVERITY, Mutation, Colonic adenomas, business, Genome-Wide Association Study
Abstract: Contains fulltext : 167193.pdf (Publisher’s version ) (Open Access) Familial adenomatous polyposis (FAP) is a dominantly inherited syndrome caused by germline mutations in the APC gene and characterized by the development of multiple colorectal adenomas and a high risk of developing colorectal cancer (CRC). The severity of polyposis is correlated with the site of the APC mutation. However, there is also phenotypic variability within families with the same underlying APC mutation, suggesting that additional factors influence the severity of polyposis. Genome-wide association studies identified several single nucleotide polymorphisms (SNPs) that are associated with CRC. We assessed whether these SNPs are associated with polyp multiplicity in proven APC mutation carriers. Sixteen CRC-associated SNPs were analysed in a cohort of 419 APC germline mutation carriers from 182 families. Clinical data were retrieved from the Dutch Polyposis Registry. Allele frequencies of the SNPs were compared for patients with /=100 adenomas, using generalized estimating equations with the APC genotype as a covariate. We found a trend of association of two of the tested SNPs with the >/=100 adenoma phenotype: the C alleles of rs16892766 at 8q23.3 (OR 1.71, 95 % CI 1.05-2.76, p = 0.03, dominant model) and rs3802842 at 11q23.1 (OR 1.51, 95 % CI 1.03-2.22, p = 0.04, dominant model). We identified two risk variants that are associated with a more severe phenotype in APC mutation carriers. These risk variants may partly explain the phenotypic variability in families with the same APC gene defect. Further studies with a larger sample size are recommended to evaluate and confirm the phenotypic effect of these SNPs in FAP.
Published: 2016

19. Do BRCA1/2 mutation carriers have an earlier onset of natural menopause?

Author: Theodora C. van Tilborg, Theo A. M. van Os, Helena C. van Doorn, Anouk Pijpe, Muriel A. Adank, Matti A. Rookus, Wendy A. G. van Zelst-Stams, Senno Verhoef, Margreet G. E. M. Ausems, Christi J. van Asperen, Encarna B. Gomez Garcia, T.M. Mooij, Jan C. Oosterwijk, Anna M. E. Bos, Frank J.M. Broekmans, Lieske H. Schrijver, Human Genetics, Damage and Repair in Cancer Development and Cancer Treatment (DARE), Targeted Gynaecologic Oncology (TARGON), Epidemiology and Data Science, Human genetics, CCA - Cancer biology, and Obstetrics & Gynecology
Subjects: Aging, Genes, BRCA2, Genes, BRCA1, Kaplan-Meier Estimate, Ovarian aging, 0302 clinical medicine, Premature Menopause, Aged, 80 and over, RISK, 030219 obstetrics & reproductive medicine, Obstetrics, Applied Mathematics, Hazard ratio, Age Factors, Obstetrics and Gynecology, WOMEN, Middle Aged, 030220 oncology & carcinogenesis, Mutation (genetic algorithm), Cohort, DNA-REPAIR, Regression Analysis, Female, Menopause, Cohort study, Rare cancers Radboud Institute for Health Sciences [Radboudumc 9], Adult, medicine.medical_specialty, Heterozygote, General Mathematics, Natural menopause, MENARCHE, 03 medical and health sciences, Surgical Menopause, Young Adult, AGE, medicine, Journal Article, Humans, BREAST-CANCER, COHORT, SALPINGO-OOPHORECTOMY, Aged, Proportional Hazards Models, Gynecology, business.industry, Proportional hazards model, BRCA mutation, PREMATURE MENOPAUSE, BRCA1/2 mutation, OVARIAN RESERVE, Cross-Sectional Studies, Mutation, business
Abstract: Contains fulltext : 168797.pdf (Publisher’s version ) (Closed access) OBJECTIVE: It has been hypothesized that BRCA1/2 mutation carriers have an earlier age at natural menopause (ANM), although to date findings are inconclusive. This study assessed the influence of BRCA mutation status on ANM, and aimed to explore the reasons of inconsistency in the literature. METHODS: Cross-sectional assessment from an ongoing nationwide cohort study among members of BRCA1/2 mutated families. Information was obtained by a standardized questionnaire. Kaplan-Meier curves were constructed, and Cox regression was used to assess the association between BRCA1/2 mutation status and ANM. Adjustments were made for birth cohort, family, smoking, use of hormonal contraceptives, and parity. RESULTS: A total of 1,208 BRCA1/2 mutation carriers and 2,211 proven noncarriers were included. Overall, no association was found between BRCA1/2 mutation status and ANM (adjusted hazard ratio [HR] = 1.06 [95% CI, 0.87-1.30]). We examined if the null finding was due to informative censoring by uptake of risk-reducing salpingo-oophorectomy. Indeed, within the oldest birth cohort, in which the percentage of surgical menopause events was lowest and comparable between carriers and noncarriers, the HR for earlier natural menopause in carriers was 1.45 (95% CI, 1.09-1.94). The second oldest birth cohort, however, demonstrated a decreased HR (0.67 [95% CI, 0.46-0.98]), and thus no trend over birth cohorts was found. CONCLUSIONS: Various types of selection bias hamper the comparison of ANM between BRCA1/2 mutation carriers and noncarriers, genetically tested in the clinic.
Published: 2016
Full Text: View/download PDF

20. Identification of independent association signals and putative functional variants for breast cancer risk through fine-scale mapping of the 12p11 locus

Author: Kenneth Offit, Hoda Anton-Culver, Ans M.W. van den Ouweland, Siranoush Manoukian, Christine L. Clarke, Kyriaki Michailidou, Antonis C. Antoniou, Maria Kabisch, Isabel dos-Santos-Silva, Douglas F. Easton, Curtis Olswold, Graham G. Giles, Tien Yin Wong, Ursula Eilber, Mads Thomassen, Christopher A. Haiman, Alice J. Sigurdson, Lothar Haeberle, Florence Menegaux, Ana Osorio, Marco Montagna, Katarzyna Jaworska-Bieniek, Eitan Friedman, Simon S. Cross, Daniel Barrowdale, Elinor J. Sawyer, Adam N. Freeman, Caroline Seynaeve, Min Hyuk Lee, Arnaud Droit, Per Hall, Minouk J. Schoemaker, Trinidad Caldés, Peter Hillemanns, Frederik Marmé, Jenny Lester, Michele M. Doody, Bernard Peissel, Peter Kraft, Elza Khusnutdinova, Anna H. Wu, Stéphanie Peeters, Georg Pfeiler, Pascal Guénel, Hidemi Ito, Xingyi Guo, Antoinette Hollestelle, Heli Nevanlinna, Kathleen Claes, Ylva Paulsson-Karlsson, Cecilia M. Dorfling, Roger L. Milne, Daehee Kang, Judith S. Brand, Diether Lambrechts, Olufunmilayo I. Olopade, Simona Agata, Saundra S. Buys, Muhammad Usman Rashid, Fabienne Lesueur, Alicia Beeghly-Fadiel, Peter Devilee, Manjeet K. Bolla, Natalia Antonenkova, Irene Konstantopoulou, Claudine Isaacs, Anja Rudolph, Carl Blomqvist, Tjoung Won Park-Simon, Judy Garber, Csilla Szabo, Francois Bacot, Arto Mannermaa, Yu-Tang Gao, Stig E. Bojesen, Susan L. Neuhausen, Marina Bermisheva, Qiuyin Cai, Zakaria Einbeigi, Christian F. Singer, Qin Wang, Kerstin Rhiem, Sofia Khan, Fiona Lalloo, Robert L. Nussbaum, Thilo Dörk, William J. Blot, Sylvie Mazoyer, Julia A. Knight, Katherine L. Nathanson, Clare Turnbull, Nazneen Rahman, Anne Lise Børresen-Dale, Chuen Neng Lee, Annegien Broeks, Martha J. Shrubsole, Ava Kwong, Jirong Long, Ian G. Campbell, Sara Margolin, Fergus J. Couch, Laima Tihomirova, Mary Beth Terry, Jenny Chang-Claude, Alice S. Whittemore, Joseph Vijai, Alfons Meindl, Xiao-Ou Shu, Shan Wang-Gohrke, Wei Zheng, Beth Y. Karlan, Jacques Simard, Angela Cox, Shahana Ahmed, Polly A. Newcomb, Ritu Salani, Chen-Yang Shen, Adalgeir Arason, Sandrine Tchatchou, Ute Hamann, Elizabeth J. van Rensburg, Michael Jones, Mark H. Greene, Anthony J. Swerdlow, Senno Verhoef, Jonine Figueroa, Hermann Brenner, Volker Arndt, Charles Joly Beauparlant, Esther M. John, Nadege Presneau, Jingmei Li, Laura Papi, Marjanka K. Schmidt, Montserrat Garcia-Closas, Uffe Birk Jensen, Georgia Chenevix-Trench, Paolo Peterlongo, Penny Soucy, Thomas Brüning, Jaana M. Hartikainen, Siddhartha Kar, Ji Yeob Choi, Manuel R. Teixeira, Phuong L. Mai, Alex Teulé, Jyh Cherng Yu, Paul Brennan, Maya Ghoussaini, Edith Olah, Henrik Flyger, Michael Friedlander, Soo Hwang Teo, Frans B. L. Hogervorst, Kathleen M. Egan, David J. Hunter, Kristiina Aittomäki, Joe Dennis, Anna González-Neira, Mikael Hartman, Alison M. Dunning, Doris Steinemann, Debra Frost, Melissa C. Southey, Ramunas Janavicius, Evgeny N. Imyanitov, Catherine M. Phelan, Amanda E. Toland, Anna Marie Mulligan, David ven den Berg, Rita K. Schmutzler, Julian Peto, Irene L. Andrulis, Chenjie Zeng, Kenneth Muir, Peter Schürmann, Saila Kauppila, Banu Arun, Jane Carpenter, Jeffrey N. Weitzel, Yael Laitman, Susan M. Domchek, Robert Winqvist, Caroline Baynes, Brita Arver, Marc Tischkowitz, Kamila Czene, Keitaro Matsuo, Barbara Burwinkel, Miriam Dwek, Kim De Leeneer, David E. Goldgar, Anna Jakubowska, Paul D.P. Pharoah, Peter A. Fasching, Bernd Dworniczak, Susan J. Ramus, Lesley McGuffog, Andrea Gehrig, Michael J. Kerin, Thomas Hansen, Francesca Damiola, John L. Hopper, Loic Le Marchand, Peter J. Hulick, Annika Lindblom, Emily Hallberg, Miguel de la Hoya, Gaetana Gambino, Martine Dumont, Susan L. Slager, Bernardo Bonanni, Bent Ejlertsen, Norhashimah Hassan, Sue Healey, Orland Diez, Mary B. Daly, Carolyn B. Hendricks, Artitaya Lophatananon, Annelie Liljegren, Steven N. Hart, Jan Lubinski, Natalia Bogdanova, Drakoulis Yannoukakos, Steve Ellis, Silje Nord, Hiltrud Brauch, Gad Rennert, Conxi Lázaro, Daniel C. Tessier, Paolo Radice, Dominique Stoppa-Lyonnet, Nadine Tung, Andrew K. Godwin, Suleeporn Sangrajrang, Karoline Kuchenbaecker, Javier Benitez, Critical care, Anesthesiology, Peri-operative and Emergency medicine (CAPE), Damage and Repair in Cancer Development and Cancer Treatment (DARE), Targeted Gynaecologic Oncology (TARGON), Medicum, Kristiina Aittomäki / Principal Investigator, Department of Medical and Clinical Genetics, Clinicum, Department of Oncology, Department of Obstetrics and Gynecology, School of Medicine / Clinical Medicine, Wang, Jean [0000-0002-9139-0627], Dennis, Joe [0000-0003-4591-1214], Tischkowitz, Marc [0000-0002-7880-0628], Pharoah, Paul [0000-0001-8494-732X], Dunning, Alison [0000-0001-6651-7166], Antoniou, Antonis [0000-0001-9223-3116], Easton, Douglas [0000-0003-2444-3247], Apollo - University of Cambridge Repository, Clinical Genetics, Medical Oncology, and Obstetrics & Gynecology
Subjects: 0301 basic medicine, Fine-scale mapping, Genome-wide association study, HORMONE-RELATED PROTEIN, Epigenesis, Genetic, Breast cancer, Medizinische Fakultät, Databases, Genetic, Genotype, BRCA2 MUTATION CARRIERS, Odds Ratio, Medicine and Health Sciences, Pair 12, Medicine, Genetic risk factor, Promoter Regions, Genetic, Medicine(all), Genetics, BRCA1 Protein, PTHLH-CCDC91, Chromosome Mapping, LOCALIZATION, Single Nucleotide, PTHLH, 3. Good health, Enhancer Elements, Genetic, Population Surveillance, Female, Medical Genetics, BRAC1 mutation carriers, CCDC91, Alleles, Breast Neoplasms, Case-Control Studies, Computational Biology, European Continental Ancestry Group, Haplotypes, Heterozygote, Humans, Mutation, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Risk, Chromosomes, Human, Pair 12, Genetic Predisposition to Disease, Genome-Wide Association Study, Human, Research Article, EXPRESSION, Enhancer Elements, SUSCEPTIBILITY LOCI, 3122 Cancers, Single-nucleotide polymorphism, Chromosomes, White People, OVARIAN-CANCER, Càncer de mama, Promoter Regions, Databases, 03 medical and health sciences, Research Support, N.I.H., Extramural, SDG 3 - Good Health and Well-being, Genetic, Journal Article, ddc:610, Polymorphism, GENOME-WIDE ASSOCIATION, Medicinsk genetik, Genetic association, Cancer och onkologi, business.industry, Haplotype, Case-control study, Biology and Life Sciences, Odds ratio, medicine.disease, ENHANCERS, 030104 developmental biology, Cancer and Oncology, METASTASIS, 3111 Biomedicine, GENETIC MODIFIERS, business, Genètica, Epigenesis
Abstract: Article, Background Multiple recent genome-wide association studies (GWAS) have identified a single nucleotide polymorphism (SNP), rs10771399, at 12p11 that is associated with breast cancer risk. Method We performed a fine-scale mapping study of a 700 kb region including 441 genotyped and more than 1300 imputed genetic variants in 48,155 cases and 43,612 controls of European descent, 6269 cases and 6624 controls of East Asian descent and 1116 cases and 932 controls of African descent in the Breast Cancer Association Consortium (BCAC; http://bcac.ccge.medschl.cam.ac.uk/), and in 15,252 BRCA1 mutation carriers in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Stepwise regression analyses were performed to identify independent association signals. Data from the Encyclopedia of DNA Elements project (ENCODE) and the Cancer Genome Atlas (TCGA) were used for functional annotation. Results Analysis of data from European descendants found evidence for four independent association signals at 12p11, represented by rs7297051 (odds ratio (OR) = 1.09, 95 % confidence interval (CI) = 1.06–1.12; P = 3 × 10-9), rs805510 (OR = 1.08, 95 % CI = 1.04–1.12, P = 2 × 10-5), and rs1871152 (OR = 1.04, 95 % CI = 1.02–1.06; P = 2 × 10-4) identified in the general populations, and rs113824616 (P = 7 × 10-5) identified in the meta-analysis of BCAC ER-negative cases and BRCA1 mutation carriers. SNPs rs7297051, rs805510 and rs113824616 were also associated with breast cancer risk at P, published version, peerReviewed
Published: 2016
Full Text: View/download PDF

21. Additional file 4: Table S5. of Identification of independent association signals and putative functional variants for breast cancer risk through fine-scale mapping of the 12p11 locus

Author: Chenjie Zeng, Xingyi Guo, Jirong Long, Kuchenbaecker, Karoline, Droit, Arnaud, Michailidou, Kyriaki, Ghoussaini, Maya, Siddhartha Kar, Freeman, Adam, Hopper, John, Milne, Roger, Bolla, Manjeet, Wang, Qin, Dennis, Joe, Agata, Simona, Shahana Ahmed, AittomĂ¤Ki, Kristiina, Andrulis, Irene, Anton-Culver, Hoda, Antonenkova, Natalia, Adalgeir Arason, Arndt, Volker, Arun, Banu, Arver, Brita, Francois Bacot, Barrowdale, Daniel, Baynes, Caroline, Beeghly-Fadiel, Alicia, Benitez, Javier, Bermisheva, Marina, Blomqvist, Carl, Blot, William, Bogdanova, Natalia, Bojesen, Stig, Bonanni, Bernardo, Anne-Lise Borresen-Dale, Brand, Judith, Brauch, Hiltrud, Brennan, Paul, Brenner, Hermann, Broeks, Annegien, BrĂźning, Thomas, Burwinkel, Barbara, Buys, Saundra, Qiuyin Cai, Caldes, Trinidad, Campbell, Ian, Carpenter, Jane, Chang-Claude, Jenny, Ji-Yeob Choi, Claes, Kathleen, Clarke, Christine, Cox, Angela, Cross, Simon, Czene, Kamila, Daly, Mary, Hoya, Miguel De La, Leeneer, Kim De, Devilee, Peter, Diez, Orland, Domchek, Susan, Doody, Michele, Dorfling, Cecilia, DĂśrk, Thilo, Dos-Santos-Silva, Isabel, Dumont, Martine, Dwek, Miriam, Dworniczak, Bernd, Egan, Kathleen, Eilber, Ursula, Einbeigi, Zakaria, Ejlertsen, Bent, Ellis, Steve, Frost, Debra, Lalloo, Fiona, Fasching, Peter, Jonine Figueroa, Flyger, Henrik, Friedlander, Michael, Friedman, Eitan, Gambino, Gaetana, Yu-Tang Gao, Garber, Judy, GarcĂA-Closas, Montserrat, Gehrig, Andrea, Damiola, Francesca, Lesueur, Fabienne, Mazoyer, Sylvie, Stoppa-Lyonnet, Dominique, Giles, Graham, Godwin, Andrew, Goldgar, David, GonzĂĄlez-Neira, Anna, Greene, Mark, GuĂŠnel, Pascal, Haeberle, Lothar, Haiman, Christopher, Hallberg, Emily, Hamann, Ute, Hansen, Thomas, Hart, Steven, Hartikainen, Jaana, Hartman, Mikael, Norhashimah Hassan, Healey, Sue, Hogervorst, Frans, Senno Verhoef, Hendricks, Carolyn, Hillemanns, Peter, Hollestelle, Antoinette, Hulick, Peter, Hunter, David, Imyanitov, Evgeny, Isaacs, Claudine, Ito, Hidemi, Jakubowska, Anna, Ramunas Janavicius, Jaworska-Bieniek, Katarzyna, Jensen, Uffe, John, Esther, Beauparlant, Charles Joly, Jones, Michael, Kabisch, Maria, Daehee Kang, Karlan, Beth, Kauppila, Saila, Kerin, Michael, Khan, Sofia, Khusnutdinova, Elza, Knight, Julia, Konstantopoulou, Irene, Kraft, Peter, Kwong, Ava, Laitman, Yael, Lambrechts, Diether, Conxi Lazaro, Loic Le Marchand, Chuen Lee, Lee, Min, Lester, Jenny, Jingmei Li, Liljegren, Annelie, Lindblom, Annika, Artitaya Lophatananon, Lubinski, Jan, Mai, Phuong, Mannermaa, Arto, Manoukian, Siranoush, Margolin, Sara, Marme, Frederik, Keitaro Matsuo, McGuffog, Lesley, Meindl, Alfons, Menegaux, Florence, Montagna, Marco, Muir, Kenneth, Mulligan, Anna, Nathanson, Katherine, Neuhausen, Susan, Nevanlinna, Heli, Newcomb, Polly, Nord, Silje, Nussbaum, Robert, Offit, Kenneth, Olah, Edith, Olufunmilayo Olopade, Olswold, Curtis, Osorio, Ana, Papi, Laura, Tjoung-Won Park-Simon, Paulsson-Karlsson, Ylva, Peeters, Stephanie, Peissel, Bernard, Peterlongo, Paolo, Peto, Julian, Pfeiler, Georg, Phelan, Catherine, Nadege Presneau, Radice, Paolo, Nazneen Rahman, Ramus, Susan, Rashid, Muhammad, Rennert, Gad, Rhiem, Kerstin, Rudolph, Anja, Salani, Ritu, Suleeporn Sangrajrang, Sawyer, Elinor, Marjanka Schmidt, Schmutzler, Rita, Minouk Schoemaker, SchĂźrmann, Peter, Seynaeve, Caroline, Shen, Chen-Yang, Shrubsole, Martha, Xiao-Ou Shu, Sigurdson, Alice, Singer, Christian, Slager, Susan, Soucy, Penny, Southey, Melissa, Steinemann, Doris, Swerdlow, Anthony, Szabo, Csilla, Tchatchou, Sandrine, Teixeira, Manuel, Teo, Soo, Terry, Mary, Tessier, Daniel, TeulĂŠ, Alex, Thomassen, Mads, Tihomirova, Laima, Tischkowitz, Marc, Toland, Amanda, Tung, Nadine, Turnbull, Clare, Ouweland, Ans Van Den, Rensburg, Elizabeth Van, Berg, David Ven Den, Vijai, Joseph, Wang-Gohrke, Shan, Weitzel, Jeffrey, Whittemore, Alice, Winqvist, Robert, Wong, Tien, Wu, Anna, Drakoulis Yannoukakos, Jyh-Cherng Yu, Pharoah, Paul, Hall, Per, Chenevix-Trench, Georgia, Dunning, Alison, Simard, Jacques, Couch, Fergus, Antoniou, Antonis, Easton, Douglas, and Zheng, Wei
Subjects: body regions, nervous system, fungi, skin and connective tissue diseases
Abstract: Associations of independent signals forÂ breast cancer risk in women of East Asian and African descent. (PDF 66 kb)
Published: 2016
Full Text: View/download PDF

22. Additional file 2: Table S3. of Identification of independent association signals and putative functional variants for breast cancer risk through fine-scale mapping of the 12p11 locus

Author: Chenjie Zeng, Xingyi Guo, Jirong Long, Kuchenbaecker, Karoline, Droit, Arnaud, Michailidou, Kyriaki, Ghoussaini, Maya, Siddhartha Kar, Freeman, Adam, Hopper, John, Milne, Roger, Bolla, Manjeet, Wang, Qin, Dennis, Joe, Agata, Simona, Shahana Ahmed, AittomĂ¤Ki, Kristiina, Andrulis, Irene, Anton-Culver, Hoda, Antonenkova, Natalia, Adalgeir Arason, Arndt, Volker, Arun, Banu, Arver, Brita, Francois Bacot, Barrowdale, Daniel, Baynes, Caroline, Beeghly-Fadiel, Alicia, Benitez, Javier, Bermisheva, Marina, Blomqvist, Carl, Blot, William, Bogdanova, Natalia, Bojesen, Stig, Bonanni, Bernardo, Anne-Lise Borresen-Dale, Brand, Judith, Brauch, Hiltrud, Brennan, Paul, Brenner, Hermann, Broeks, Annegien, BrĂźning, Thomas, Burwinkel, Barbara, Buys, Saundra, Qiuyin Cai, Caldes, Trinidad, Campbell, Ian, Carpenter, Jane, Chang-Claude, Jenny, Ji-Yeob Choi, Claes, Kathleen, Clarke, Christine, Cox, Angela, Cross, Simon, Czene, Kamila, Daly, Mary, Hoya, Miguel De La, Leeneer, Kim De, Devilee, Peter, Diez, Orland, Domchek, Susan, Doody, Michele, Dorfling, Cecilia, DĂśrk, Thilo, Dos-Santos-Silva, Isabel, Dumont, Martine, Dwek, Miriam, Dworniczak, Bernd, Egan, Kathleen, Eilber, Ursula, Einbeigi, Zakaria, Ejlertsen, Bent, Ellis, Steve, Frost, Debra, Lalloo, Fiona, Fasching, Peter, Jonine Figueroa, Flyger, Henrik, Friedlander, Michael, Friedman, Eitan, Gambino, Gaetana, Yu-Tang Gao, Garber, Judy, GarcĂA-Closas, Montserrat, Gehrig, Andrea, Damiola, Francesca, Lesueur, Fabienne, Mazoyer, Sylvie, Stoppa-Lyonnet, Dominique, Giles, Graham, Godwin, Andrew, Goldgar, David, GonzĂĄlez-Neira, Anna, Greene, Mark, GuĂŠnel, Pascal, Haeberle, Lothar, Haiman, Christopher, Hallberg, Emily, Hamann, Ute, Hansen, Thomas, Hart, Steven, Hartikainen, Jaana, Hartman, Mikael, Norhashimah Hassan, Healey, Sue, Hogervorst, Frans, Senno Verhoef, Hendricks, Carolyn, Hillemanns, Peter, Hollestelle, Antoinette, Hulick, Peter, Hunter, David, Imyanitov, Evgeny, Isaacs, Claudine, Ito, Hidemi, Jakubowska, Anna, Ramunas Janavicius, Jaworska-Bieniek, Katarzyna, Jensen, Uffe, John, Esther, Beauparlant, Charles Joly, Jones, Michael, Kabisch, Maria, Daehee Kang, Karlan, Beth, Kauppila, Saila, Kerin, Michael, Khan, Sofia, Khusnutdinova, Elza, Knight, Julia, Konstantopoulou, Irene, Kraft, Peter, Kwong, Ava, Laitman, Yael, Lambrechts, Diether, Conxi Lazaro, Loic Le Marchand, Chuen Lee, Lee, Min, Lester, Jenny, Jingmei Li, Liljegren, Annelie, Lindblom, Annika, Artitaya Lophatananon, Lubinski, Jan, Mai, Phuong, Mannermaa, Arto, Manoukian, Siranoush, Margolin, Sara, Marme, Frederik, Keitaro Matsuo, McGuffog, Lesley, Meindl, Alfons, Menegaux, Florence, Montagna, Marco, Muir, Kenneth, Mulligan, Anna, Nathanson, Katherine, Neuhausen, Susan, Nevanlinna, Heli, Newcomb, Polly, Nord, Silje, Nussbaum, Robert, Offit, Kenneth, Olah, Edith, Olufunmilayo Olopade, Olswold, Curtis, Osorio, Ana, Papi, Laura, Tjoung-Won Park-Simon, Paulsson-Karlsson, Ylva, Peeters, Stephanie, Peissel, Bernard, Peterlongo, Paolo, Peto, Julian, Pfeiler, Georg, Phelan, Catherine, Nadege Presneau, Radice, Paolo, Nazneen Rahman, Ramus, Susan, Rashid, Muhammad, Rennert, Gad, Rhiem, Kerstin, Rudolph, Anja, Salani, Ritu, Suleeporn Sangrajrang, Sawyer, Elinor, Marjanka Schmidt, Schmutzler, Rita, Minouk Schoemaker, SchĂźrmann, Peter, Seynaeve, Caroline, Shen, Chen-Yang, Shrubsole, Martha, Xiao-Ou Shu, Sigurdson, Alice, Singer, Christian, Slager, Susan, Soucy, Penny, Southey, Melissa, Steinemann, Doris, Swerdlow, Anthony, Szabo, Csilla, Tchatchou, Sandrine, Teixeira, Manuel, Teo, Soo, Terry, Mary, Tessier, Daniel, TeulĂŠ, Alex, Thomassen, Mads, Tihomirova, Laima, Tischkowitz, Marc, Toland, Amanda, Tung, Nadine, Turnbull, Clare, Ouweland, Ans Van Den, Rensburg, Elizabeth Van, Berg, David Ven Den, Vijai, Joseph, Wang-Gohrke, Shan, Weitzel, Jeffrey, Whittemore, Alice, Winqvist, Robert, Wong, Tien, Wu, Anna, Drakoulis Yannoukakos, Jyh-Cherng Yu, Pharoah, Paul, Hall, Per, Chenevix-Trench, Georgia, Dunning, Alison, Simard, Jacques, Couch, Fergus, Antoniou, Antonis, Easton, Douglas, and Zheng, Wei
Abstract: Independent association signals for risk ofÂ estrogen (ER)-positive and ER-negative breast cancer in European descendants. (PDFÂ 47 kb)
Published: 2016
Full Text: View/download PDF

23. Additional file 6: Table S6. of Identification of independent association signals and putative functional variants for breast cancer risk through fine-scale mapping of the 12p11 locus

Author: Chenjie Zeng, Xingyi Guo, Jirong Long, Kuchenbaecker, Karoline, Droit, Arnaud, Michailidou, Kyriaki, Ghoussaini, Maya, Siddhartha Kar, Freeman, Adam, Hopper, John, Milne, Roger, Bolla, Manjeet, Wang, Qin, Dennis, Joe, Agata, Simona, Shahana Ahmed, AittomĂ¤Ki, Kristiina, Andrulis, Irene, Anton-Culver, Hoda, Antonenkova, Natalia, Adalgeir Arason, Arndt, Volker, Arun, Banu, Arver, Brita, Francois Bacot, Barrowdale, Daniel, Baynes, Caroline, Beeghly-Fadiel, Alicia, Benitez, Javier, Bermisheva, Marina, Blomqvist, Carl, Blot, William, Bogdanova, Natalia, Bojesen, Stig, Bonanni, Bernardo, Anne-Lise Borresen-Dale, Brand, Judith, Brauch, Hiltrud, Brennan, Paul, Brenner, Hermann, Broeks, Annegien, BrĂźning, Thomas, Burwinkel, Barbara, Buys, Saundra, Qiuyin Cai, Caldes, Trinidad, Campbell, Ian, Carpenter, Jane, Chang-Claude, Jenny, Ji-Yeob Choi, Claes, Kathleen, Clarke, Christine, Cox, Angela, Cross, Simon, Czene, Kamila, Daly, Mary, Hoya, Miguel De La, Leeneer, Kim De, Devilee, Peter, Diez, Orland, Domchek, Susan, Doody, Michele, Dorfling, Cecilia, DĂśrk, Thilo, Dos-Santos-Silva, Isabel, Dumont, Martine, Dwek, Miriam, Dworniczak, Bernd, Egan, Kathleen, Eilber, Ursula, Einbeigi, Zakaria, Ejlertsen, Bent, Ellis, Steve, Frost, Debra, Lalloo, Fiona, Fasching, Peter, Jonine Figueroa, Flyger, Henrik, Friedlander, Michael, Friedman, Eitan, Gambino, Gaetana, Yu-Tang Gao, Garber, Judy, GarcĂA-Closas, Montserrat, Gehrig, Andrea, Damiola, Francesca, Lesueur, Fabienne, Mazoyer, Sylvie, Stoppa-Lyonnet, Dominique, Giles, Graham, Godwin, Andrew, Goldgar, David, GonzĂĄlez-Neira, Anna, Greene, Mark, GuĂŠnel, Pascal, Haeberle, Lothar, Haiman, Christopher, Hallberg, Emily, Hamann, Ute, Hansen, Thomas, Hart, Steven, Hartikainen, Jaana, Hartman, Mikael, Norhashimah Hassan, Healey, Sue, Hogervorst, Frans, Senno Verhoef, Hendricks, Carolyn, Hillemanns, Peter, Hollestelle, Antoinette, Hulick, Peter, Hunter, David, Imyanitov, Evgeny, Isaacs, Claudine, Ito, Hidemi, Jakubowska, Anna, Ramunas Janavicius, Jaworska-Bieniek, Katarzyna, Jensen, Uffe, John, Esther, Beauparlant, Charles Joly, Jones, Michael, Kabisch, Maria, Daehee Kang, Karlan, Beth, Kauppila, Saila, Kerin, Michael, Khan, Sofia, Khusnutdinova, Elza, Knight, Julia, Konstantopoulou, Irene, Kraft, Peter, Kwong, Ava, Laitman, Yael, Lambrechts, Diether, Conxi Lazaro, Loic Le Marchand, Chuen Lee, Lee, Min, Lester, Jenny, Jingmei Li, Liljegren, Annelie, Lindblom, Annika, Artitaya Lophatananon, Lubinski, Jan, Mai, Phuong, Mannermaa, Arto, Manoukian, Siranoush, Margolin, Sara, Marme, Frederik, Keitaro Matsuo, McGuffog, Lesley, Meindl, Alfons, Menegaux, Florence, Montagna, Marco, Muir, Kenneth, Mulligan, Anna, Nathanson, Katherine, Neuhausen, Susan, Nevanlinna, Heli, Newcomb, Polly, Nord, Silje, Nussbaum, Robert, Offit, Kenneth, Olah, Edith, Olufunmilayo Olopade, Olswold, Curtis, Osorio, Ana, Papi, Laura, Tjoung-Won Park-Simon, Paulsson-Karlsson, Ylva, Peeters, Stephanie, Peissel, Bernard, Peterlongo, Paolo, Peto, Julian, Pfeiler, Georg, Phelan, Catherine, Nadege Presneau, Radice, Paolo, Nazneen Rahman, Ramus, Susan, Rashid, Muhammad, Rennert, Gad, Rhiem, Kerstin, Rudolph, Anja, Salani, Ritu, Suleeporn Sangrajrang, Sawyer, Elinor, Marjanka Schmidt, Schmutzler, Rita, Minouk Schoemaker, SchĂźrmann, Peter, Seynaeve, Caroline, Shen, Chen-Yang, Shrubsole, Martha, Xiao-Ou Shu, Sigurdson, Alice, Singer, Christian, Slager, Susan, Soucy, Penny, Southey, Melissa, Steinemann, Doris, Swerdlow, Anthony, Szabo, Csilla, Tchatchou, Sandrine, Teixeira, Manuel, Teo, Soo, Terry, Mary, Tessier, Daniel, TeulĂŠ, Alex, Thomassen, Mads, Tihomirova, Laima, Tischkowitz, Marc, Toland, Amanda, Tung, Nadine, Turnbull, Clare, Ouweland, Ans Van Den, Rensburg, Elizabeth Van, Berg, David Ven Den, Vijai, Joseph, Wang-Gohrke, Shan, Weitzel, Jeffrey, Whittemore, Alice, Winqvist, Robert, Wong, Tien, Wu, Anna, Drakoulis Yannoukakos, Jyh-Cherng Yu, Pharoah, Paul, Hall, Per, Chenevix-Trench, Georgia, Dunning, Alison, Simard, Jacques, Couch, Fergus, Antoniou, Antonis, Easton, Douglas, and Zheng, Wei
Subjects: body regions, nervous system, fungi
Abstract: Putative functional SNPs identified using the ENCODE data. (PDF 50 kb)
Published: 2016
Full Text: View/download PDF

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

Author: Agnieszka Dansonka-Mieszkowska, Angela Brooks-Wilson, Ingo B. Runnebaum, Kenneth Offit, Melissa C. Southey, Ramunas Janavicius, Finn Cilius Nielsen, Christine Maugard, Marco Montagna, Annette Fontaine, Janusz Menkiszak, Robert Winqvist, Pascal Guénel, Rosalind Glasspool, Usha Menon, Daniel Barrowdale, Elinor J. Sawyer, Anna Jakubowska, Paul D.P. Pharoah, Martha J. Shrubsole, Lambertus A. Kiemeney, Camilla Krakstad, Dong Liang, Minouk J. Schoemaker, Judith S. Brand, Joseph Vijai, Marc T. Goodman, Thomas A. Sellers, David Van Den Berg, Celeste Leigh Pearce, Alice S. Whittemore, Irene L. Andrulis, Radka Platte, Kunle Odunsi, Orland Diez, Estrid Høgdall, Brooke L. Fridley, C. J. van Asperen, Mary Anne Rossing, Vessela N. Kristensen, Jonathan Tyrer, Tara M. Friebel, Douglas F. Easton, Per Hall, Mads Thomassen, Christine Walsh, Thilo Dörk, Louise A. Brinton, Keith Humphreys, Douglas A. Levine, Allison F. Vitonis, Anna H. Wu, Hermann Brenner, Maria Bisogna, Joellen M. Schildkraut, Maria A. Caligo, Jonine D. Figueroa, Lynne R. Wilkens, Grace Friel, Michael G. Schrauder, Evgeny N. Imyanitov, Sune F. Nielsen, Sylvie Mazoyer, Diana Eccles, Andrew Berchuck, Sara Margolin, Mitul Shah, Matthias W. Beckmann, Elizabeth M. Poole, Gad Rennert, Arif B. Ekici, Elisa Alducci, Bjarni A. Agnarsson, Linda S. Cook, Javier Benitez, Paolo Peterlongo, Natalia Antonenkova, Annika Lindblom, Patrick Neven, Julia A. Knight, Alan Ashworth, Matti A. Rookus, Frans B. L. Hogervorst, Daniela Zaffaroni, Banu Arun, Sue Healey, Robert P. Edwards, Susanne K. Kjaer, Laura J. van't Veer, John W.M. Martens, Christa Stegmaier, Claudine Isaacs, Daniel W. Cramer, Lars Beckmann, Liisa M. Pelttari, Dieter Flesch-Janys, Irene Orlow, Atocha Romero, Diana Torres, Marjanka K. Schmidt, Simon S. Cross, Alison M. Dunning, Rosemary L. Balleine, Sandra L. Halverson, Benoit Beuselinck, Melissa C. Larson, Senno Verhoef, Jirong Long, Angela Cox, Maartje J. Hooning, Bruce Poppe, Katarzyna Jaworska, Jolanta Kupryjanczyk, Nicolas Wentzensen, Gustavo C. Rodriguez, Tanja Pejovic, Roberta B. Ness, James Paul, Dominique Stoppa-Lyonnet, Nadine Tung, Gianluca Severi, Malcolm C. Pike, Hoda Anton-Culver, Ans M.W. van den Ouweland, Mark E. Robson, Roger L. Milne, Jan C. Oosterwijk, Laima Tihomirova, Helen Tsimiklis, Pierre Laurent-Puig, Florian Heitz, Beth Y. Karlan, Ian Tomlinson, Thérèse Truong, Bernardo Bonanni, Frederik Marmé, Qin Wang, Conxi Lázaro, Volker Arndt, Antoinette Hollestelle, Jacek Gronwald, M. Pilar Zamora, Barbara Wappenschmidt, Maren Weischer, Veli-Matti Kosma, Giulietta Scuvera, Jenny Lester, Andreas Berger, Stephen J. Chanock, Line Bjørge, Anthony J. Swerdlow, Andrew K. Godwin, Mervi Grip, Amanda E. Toland, Anna Marie Mulligan, Noralane M. Lindor, Paolo Radice, Bent Ejlertsen, Frederieke H. van der Baan, Lothar Haeberle, Valerie McGuire, Kamila Czene, Rob A. E. M. Tollenaar, Maria Soller, Katherine L. Nathanson, Sandrina Lambrechts, Susan J. Ramus, Anja Rudolph, Penny Soucy, Caroline Weltens, Hiltrud Brauch, Olivia Fletcher, Sara H. Olson, Yael Laitman, Marion Piedmonte, Arto Mannermaa, Agnieszka Budzilowska, Olga M. Sinilnikova, Christian F. Singer, Cezary Cybulski, Weiva Sieh, Ed Dicks, Elizabeth J. van Rensburg, Isabel dos Santos Silva, Hans Ehrencrona, Timothy R. Rebbeck, Jaana M. Hartikainen, Sandra Orsulic, Jingmei Li, Carmel Apicella, Anna deFazio, Ian G. Campbell, Ignace Vergote, Rita K. Schmutzler, Fredrick R. Schumacher, Julian Peto, Nadeem Siddiqui, Brian E. Henderson, Starr R. Guzman, Maria Kabisch, John L. Hopper, Arto Leminen, Jeffrey N. Weitzel, Honglin Song, J. Margriet Collée, Ingvild L. Tangen, Børge G. Nordestgaard, Antonis C. Antoniou, Lara Sucheston, Helena C. van Doorn, Lídia Feliubadaló, Leon F.A.G. Massuger, Iain A. McNeish, Nichola Johnson, Simon A. Gayther, Jennifer A. Doherty, Anders Bojesen, Gord Glendon, Yukie Bean, Celine M. Vachon, Barbara Burwinkel, Edith Olah, Shan Wang-Gohrke, Brita Arver, Marc Tischkowitz, Arja Jukkola-Vuorinen, Martin Gore, Vesa Kataja, Nicola Miller, Pamela J. Thompson, Malcolm W.R. Reed, Michelle A.T. Hildebrandt, Ritu Salani, Janet E. Olson, Catriona McLean, Cecilia M. Dorfling, Georgia Chenevix-Trench, Frederique Mariette, Laura Ottini, Fergus J. Couch, Linda E. Kelemen, Nhu D. Le, Michael J. Kerin, Claus Høgdall, Miguel de la Hoya, Jonathan Carter, Mercedes Durán, Inge Søkilde Pedersen, Julie M. Cunningham, Manjeet K. Bolla, Galina Lurie, Loic Le Marchand, Ute Hamann, Muy-Kheng Tea, Karoline Kuchenbaecker, Irene Konstantopoulou, Thomas Hansen, Francesca Damiola, Stefano Fortuzzi, Shelley S. Tworoger, Mikael Eriksson, Carl Blomqvist, Joan Brunet, Allan Jensen, Karen Lu, Elisa V. Bandera, Anne M. van Altena, Anne-Marie Gerdes, Lene Lundvall, Susan L. Neuhausen, Wei Zheng, Ana Osorio, Fiona Bruinsma, Hannah P. Yang, Graham G. Giles, Christoph Engel, Nick Orr, Harvey A. Risch, Jan Lubinski, Jacoba P. Knol-Bout, Phuong L. Mai, Martine Dumont, Xifeng Wu, Christof Sohn, Noah D. Kauff, Kristiina Aittomäki, Natalia Bogdanova, Alexander Hein, Francesmary Modugno, Heli Nevanlinna, Helga B. Salvesen, Adriana Lasa, Daphne Gschwantler Kaulich, Dominiek Smeets, Jenny Permuth-Wey, Josef Herzog, Catherine M. Phelan, Clareann H. Bunker, Steve Ellis, Christopher A. Haiman, Jolanta Lissowska, Judy Garber, Joanna Plisiecka-Halasa, Robert A. Vierkant, Steven A. Narod, Mark H. Greene, Florence Menegaux, Norbert Arnold, Primitiva Menéndez, Robert L. Nussbaum, Katja K.H. Aben, Andreas Schneeweiss, Katri Pylkäs, Els Van Nieuwenhuysen, Tomasz Huzarski, Joe Dennis, Susan M. Domchek, Andreas du Bois, Aleksandra Gentry-Maharaj, Florentia Fostira, Mary Beth Terry, Jenny Chang-Claude, Eitan Friedman, Argyrios Ziogas, Hatef Darabi, Kathleen Claes, Ellen L. Goode, Olufunmilayo I. Olopade, Stig E. Bojesen, Jo Perkins, Raanan Berger, Sharon E. Johnatty, Taru A. Muranen, Montserrat Garcia-Closas, Uffe Birk Jensen, Thomas Brüning, Heiko Müller, Debra Frost, Peter A. Fasching, Lesley McGuffog, Diether Lambrechts, Kelly-Anne Phillips, Caroline M. Seynaeve, Kathryn L. Terry, Ira Schwaab, Ralf Bützow, Manuel R. Teixeira, Joseph H. Rothstein, Bernard Peissel, Anna von Wachenfeldt, Saundra S. Buys, Peter Devilee, Alfons Meindl, Laura Baglietto, Kirsten B. Moysich, Arjen R. Mensenkamp, Philipp Harter, Jacques Simard, Generalitat de Catalunya, Ministerio de Ciencia e Innovación (España), Fundación Mutua Madrileña, Asociación Española Contra el Cáncer, Instituto de Salud Carlos III, National Institutes of Health (US), Wellcome Trust, European Commission, National Cancer Institute (US), Medical Oncology, Clinical Genetics, Erasmus MC other, Pediatric Surgery, Pathology, and Neurology
Subjects: 0301 basic medicine, Oncology, endocrine system diseases, Endometriosis, Breast cancer, Clinical outcome, Genetic association, KRAS variant, Ovarian cancer, Genome-wide association study, Carcinoma, Ovarian Epithelial, medicine.disease_cause, Prostate, Brjóstakrabbamein, Clinical outcomes, Genotype, Obstetrics and Gynaecology, Tumours of the digestive tract Radboud Institute for Molecular Life Sciences [Radboudumc 14], PROSTATE, Neoplasms, Glandular and Epithelial, skin and connective tissue diseases, RISK, Ovarian Neoplasms, Women's cancers Radboud Institute for Molecular Life Sciences [Radboudumc 17], Obstetrics and Gynecology, WOMEN, female genital diseases and pregnancy complications, 3. Good health, medicine.anatomical_structure, Treatment Outcome, Urological cancers Radboud Institute for Health Sciences [Radboudumc 15], Female, KRAS, medicine.medical_specialty, SUSCEPTIBILITY LOCI, Breast Neoplasms, Article, Proto-Oncogene Proteins p21(ras), 03 medical and health sciences, SDG 3 - Good Health and Well-being, Internal medicine, medicine, Carcinoma, Humans, GENOME-WIDE ASSOCIATION, Genetic Association Studies, POLYMORPHISMS, Krabbamein, MICRORNA-BINDING-SITE, IDENTIFICATION, business.industry, ENDOMETRIOSIS, Arfgengi, medicine.disease, 030104 developmental biology, PTT12, Eggjastokkar, business
Abstract: Ovarian Cancer Association Consortium, Breast Cancer Association Consortium, and Consortium of Modifiers of BRCA1 and BRCA2: et al., [Objective]: Clinical genetic testing is commercially available for rs61764370, an inherited variant residing in a KRAS 3' UTR microRNA binding site, based on suggested associations with increased ovarian and breast cancer risk as well as with survival time. However, prior studies, emphasizing particular subgroups, were relatively small. Therefore, we comprehensively evaluated ovarian and breast cancer risks as well as clinical outcome associated with rs61764370. [Methods]: Centralized genotyping and analysis were performed for 140,012 women enrolled in the Ovarian Cancer Association Consortium (15,357 ovarian cancer patients; 30,816 controls), the Breast Cancer Association Consortium (33,530 breast cancer patients; 37,640 controls), and the Consortium of Modifiers of BRCA1 and BRCA2 (14,765 BRCA1 and 7904 BRCA2 mutation carriers). [Results]: We found no association with risk of ovarian cancer (OR = 0.99, 95% CI 0.94-1.04, p = 0.74) or breast cancer (OR = 0.98, 95% CI 0.94-1.01, p = 0.19) and results were consistent among mutation carriers (BRCA1, ovarian cancer HR = 1.09, 95% CI 0.97-1.23, p = 0.14, breast cancer HR = 1.04, 95% CI 0.97-1.12, p = 0.27; BRCA2, ovarian cancer HR = 0.89, 95% CI 0.71-1.13, p = 0.34, breast cancer HR = 1.06, 95% CI 0.94-1.19, p = 0.35). Null results were also obtained for associations with overall survival following ovarian cancer (HR = 0.94, 95% CI 0.83-1.07, p = 0.38), breast cancer (HR = 0.96, 95% CI 0.87-1.06, p = 0.38), and all other previously-reported associations. [Conclusions]: rs61764370 is not associated with risk of ovarian or breast cancer nor with clinical outcome for patients with these cancers. Therefore, genotyping this variant has no clinical utility related to the prediction or management of these cancers., The COGS project is funded through a European Commission's Seventh Framework Programme grant (agreement number 223175 — HEALTH-F2-2009-223175). The scientific development and funding for this project were in part supported by the US National Cancer Institute GAME-ON Post-GWAS Initiative (U19-CA148112). Funding for the project was provided by the Wellcome Trust under award 076113. This work was partially supported by Spanish Association against Cancer (AECC08), RTICC 06/0020/1060, FISPI08/1120, Mutua Madrileña Foundation (FMMA) and SAF2010-20493. Was supported by a grant RD12/00369/0006 and 12/00539 from ISCIII (Spain), partially supported by European Regional Development FEDER funds. Contract grant sponsor: Asociación Española Contra el Cáncer, Spanish Health Research Fund; Carlos III Health Institute; Catalan Health Institute and Autonomous Government of Catalonia. Contract grant numbers: ISCIIIRETIC RD06/0020/1051, RD12/0036/008, PI10/01422, PI10/00748, PI13/00285 and 2009SGR290.
Published: 2016
Full Text: View/download PDF

25. Additional file 7: Table S7. of Identification of independent association signals and putative functional variants for breast cancer risk through fine-scale mapping of the 12p11 locus

Author: Chenjie Zeng, Xingyi Guo, Jirong Long, Kuchenbaecker, Karoline, Droit, Arnaud, Michailidou, Kyriaki, Ghoussaini, Maya, Siddhartha Kar, Freeman, Adam, Hopper, John, Milne, Roger, Bolla, Manjeet, Wang, Qin, Dennis, Joe, Agata, Simona, Shahana Ahmed, AittomĂ¤Ki, Kristiina, Andrulis, Irene, Anton-Culver, Hoda, Antonenkova, Natalia, Adalgeir Arason, Arndt, Volker, Arun, Banu, Arver, Brita, Francois Bacot, Barrowdale, Daniel, Baynes, Caroline, Beeghly-Fadiel, Alicia, Benitez, Javier, Bermisheva, Marina, Blomqvist, Carl, Blot, William, Bogdanova, Natalia, Bojesen, Stig, Bonanni, Bernardo, Anne-Lise Borresen-Dale, Brand, Judith, Brauch, Hiltrud, Brennan, Paul, Brenner, Hermann, Broeks, Annegien, BrĂźning, Thomas, Burwinkel, Barbara, Buys, Saundra, Qiuyin Cai, Caldes, Trinidad, Campbell, Ian, Carpenter, Jane, Chang-Claude, Jenny, Ji-Yeob Choi, Claes, Kathleen, Clarke, Christine, Cox, Angela, Cross, Simon, Czene, Kamila, Daly, Mary, Hoya, Miguel De La, Leeneer, Kim De, Devilee, Peter, Diez, Orland, Domchek, Susan, Doody, Michele, Dorfling, Cecilia, DĂśrk, Thilo, Dos-Santos-Silva, Isabel, Dumont, Martine, Dwek, Miriam, Dworniczak, Bernd, Egan, Kathleen, Eilber, Ursula, Einbeigi, Zakaria, Ejlertsen, Bent, Ellis, Steve, Frost, Debra, Lalloo, Fiona, Fasching, Peter, Jonine Figueroa, Flyger, Henrik, Friedlander, Michael, Friedman, Eitan, Gambino, Gaetana, Yu-Tang Gao, Garber, Judy, GarcĂA-Closas, Montserrat, Gehrig, Andrea, Damiola, Francesca, Lesueur, Fabienne, Mazoyer, Sylvie, Stoppa-Lyonnet, Dominique, Giles, Graham, Godwin, Andrew, Goldgar, David, GonzĂĄlez-Neira, Anna, Greene, Mark, GuĂŠnel, Pascal, Haeberle, Lothar, Haiman, Christopher, Hallberg, Emily, Hamann, Ute, Hansen, Thomas, Hart, Steven, Hartikainen, Jaana, Hartman, Mikael, Norhashimah Hassan, Healey, Sue, Hogervorst, Frans, Senno Verhoef, Hendricks, Carolyn, Hillemanns, Peter, Hollestelle, Antoinette, Hulick, Peter, Hunter, David, Imyanitov, Evgeny, Isaacs, Claudine, Ito, Hidemi, Jakubowska, Anna, Ramunas Janavicius, Jaworska-Bieniek, Katarzyna, Jensen, Uffe, John, Esther, Beauparlant, Charles Joly, Jones, Michael, Kabisch, Maria, Daehee Kang, Karlan, Beth, Kauppila, Saila, Kerin, Michael, Khan, Sofia, Khusnutdinova, Elza, Knight, Julia, Konstantopoulou, Irene, Kraft, Peter, Kwong, Ava, Laitman, Yael, Lambrechts, Diether, Conxi Lazaro, Loic Le Marchand, Chuen Lee, Lee, Min, Lester, Jenny, Jingmei Li, Liljegren, Annelie, Lindblom, Annika, Artitaya Lophatananon, Lubinski, Jan, Mai, Phuong, Mannermaa, Arto, Manoukian, Siranoush, Margolin, Sara, Marme, Frederik, Keitaro Matsuo, McGuffog, Lesley, Meindl, Alfons, Menegaux, Florence, Montagna, Marco, Muir, Kenneth, Mulligan, Anna, Nathanson, Katherine, Neuhausen, Susan, Nevanlinna, Heli, Newcomb, Polly, Nord, Silje, Nussbaum, Robert, Offit, Kenneth, Olah, Edith, Olufunmilayo Olopade, Olswold, Curtis, Osorio, Ana, Papi, Laura, Tjoung-Won Park-Simon, Paulsson-Karlsson, Ylva, Peeters, Stephanie, Peissel, Bernard, Peterlongo, Paolo, Peto, Julian, Pfeiler, Georg, Phelan, Catherine, Nadege Presneau, Radice, Paolo, Nazneen Rahman, Ramus, Susan, Rashid, Muhammad, Rennert, Gad, Rhiem, Kerstin, Rudolph, Anja, Salani, Ritu, Suleeporn Sangrajrang, Sawyer, Elinor, Marjanka Schmidt, Schmutzler, Rita, Minouk Schoemaker, SchĂźrmann, Peter, Seynaeve, Caroline, Shen, Chen-Yang, Shrubsole, Martha, Xiao-Ou Shu, Sigurdson, Alice, Singer, Christian, Slager, Susan, Soucy, Penny, Southey, Melissa, Steinemann, Doris, Swerdlow, Anthony, Szabo, Csilla, Tchatchou, Sandrine, Teixeira, Manuel, Teo, Soo, Terry, Mary, Tessier, Daniel, TeulĂŠ, Alex, Thomassen, Mads, Tihomirova, Laima, Tischkowitz, Marc, Toland, Amanda, Tung, Nadine, Turnbull, Clare, Ouweland, Ans Van Den, Rensburg, Elizabeth Van, Berg, David Ven Den, Vijai, Joseph, Wang-Gohrke, Shan, Weitzel, Jeffrey, Whittemore, Alice, Winqvist, Robert, Wong, Tien, Wu, Anna, Drakoulis Yannoukakos, Jyh-Cherng Yu, Pharoah, Paul, Hall, Per, Chenevix-Trench, Georgia, Dunning, Alison, Simard, Jacques, Couch, Fergus, Antoniou, Antonis, Easton, Douglas, and Zheng, Wei
Subjects: fungi
Abstract: Gene expression analysis for putative functional SNPs using 1,006 breast tumor samples in TCGA. (PDF 46 kb)
Published: 2016
Full Text: View/download PDF

26. Additional file 3: Table S4. of Identification of independent association signals and putative functional variants for breast cancer risk through fine-scale mapping of the 12p11 locus

Author: Chenjie Zeng, Xingyi Guo, Jirong Long, Kuchenbaecker, Karoline, Droit, Arnaud, Michailidou, Kyriaki, Ghoussaini, Maya, Siddhartha Kar, Freeman, Adam, Hopper, John, Milne, Roger, Bolla, Manjeet, Wang, Qin, Dennis, Joe, Agata, Simona, Shahana Ahmed, AittomĂ¤Ki, Kristiina, Andrulis, Irene, Anton-Culver, Hoda, Antonenkova, Natalia, Adalgeir Arason, Arndt, Volker, Arun, Banu, Arver, Brita, Francois Bacot, Barrowdale, Daniel, Baynes, Caroline, Beeghly-Fadiel, Alicia, Benitez, Javier, Bermisheva, Marina, Blomqvist, Carl, Blot, William, Bogdanova, Natalia, Bojesen, Stig, Bonanni, Bernardo, Anne-Lise Borresen-Dale, Brand, Judith, Brauch, Hiltrud, Brennan, Paul, Brenner, Hermann, Broeks, Annegien, BrĂźning, Thomas, Burwinkel, Barbara, Buys, Saundra, Qiuyin Cai, Caldes, Trinidad, Campbell, Ian, Carpenter, Jane, Chang-Claude, Jenny, Ji-Yeob Choi, Claes, Kathleen, Clarke, Christine, Cox, Angela, Cross, Simon, Czene, Kamila, Daly, Mary, Hoya, Miguel De La, Leeneer, Kim De, Devilee, Peter, Diez, Orland, Domchek, Susan, Doody, Michele, Dorfling, Cecilia, DĂśrk, Thilo, Dos-Santos-Silva, Isabel, Dumont, Martine, Dwek, Miriam, Dworniczak, Bernd, Egan, Kathleen, Eilber, Ursula, Einbeigi, Zakaria, Ejlertsen, Bent, Ellis, Steve, Frost, Debra, Lalloo, Fiona, Fasching, Peter, Jonine Figueroa, Flyger, Henrik, Friedlander, Michael, Friedman, Eitan, Gambino, Gaetana, Yu-Tang Gao, Garber, Judy, GarcĂA-Closas, Montserrat, Gehrig, Andrea, Damiola, Francesca, Lesueur, Fabienne, Mazoyer, Sylvie, Stoppa-Lyonnet, Dominique, Giles, Graham, Godwin, Andrew, Goldgar, David, GonzĂĄlez-Neira, Anna, Greene, Mark, GuĂŠnel, Pascal, Haeberle, Lothar, Haiman, Christopher, Hallberg, Emily, Hamann, Ute, Hansen, Thomas, Hart, Steven, Hartikainen, Jaana, Hartman, Mikael, Norhashimah Hassan, Healey, Sue, Hogervorst, Frans, Senno Verhoef, Hendricks, Carolyn, Hillemanns, Peter, Hollestelle, Antoinette, Hulick, Peter, Hunter, David, Imyanitov, Evgeny, Isaacs, Claudine, Ito, Hidemi, Jakubowska, Anna, Ramunas Janavicius, Jaworska-Bieniek, Katarzyna, Jensen, Uffe, John, Esther, Beauparlant, Charles Joly, Jones, Michael, Kabisch, Maria, Daehee Kang, Karlan, Beth, Kauppila, Saila, Kerin, Michael, Khan, Sofia, Khusnutdinova, Elza, Knight, Julia, Konstantopoulou, Irene, Kraft, Peter, Kwong, Ava, Laitman, Yael, Lambrechts, Diether, Conxi Lazaro, Loic Le Marchand, Chuen Lee, Lee, Min, Lester, Jenny, Jingmei Li, Liljegren, Annelie, Lindblom, Annika, Artitaya Lophatananon, Lubinski, Jan, Mai, Phuong, Mannermaa, Arto, Manoukian, Siranoush, Margolin, Sara, Marme, Frederik, Keitaro Matsuo, McGuffog, Lesley, Meindl, Alfons, Menegaux, Florence, Montagna, Marco, Muir, Kenneth, Mulligan, Anna, Nathanson, Katherine, Neuhausen, Susan, Nevanlinna, Heli, Newcomb, Polly, Nord, Silje, Nussbaum, Robert, Offit, Kenneth, Olah, Edith, Olufunmilayo Olopade, Olswold, Curtis, Osorio, Ana, Papi, Laura, Tjoung-Won Park-Simon, Paulsson-Karlsson, Ylva, Peeters, Stephanie, Peissel, Bernard, Peterlongo, Paolo, Peto, Julian, Pfeiler, Georg, Phelan, Catherine, Nadege Presneau, Radice, Paolo, Nazneen Rahman, Ramus, Susan, Rashid, Muhammad, Rennert, Gad, Rhiem, Kerstin, Rudolph, Anja, Salani, Ritu, Suleeporn Sangrajrang, Sawyer, Elinor, Marjanka Schmidt, Schmutzler, Rita, Minouk Schoemaker, SchĂźrmann, Peter, Seynaeve, Caroline, Shen, Chen-Yang, Shrubsole, Martha, Xiao-Ou Shu, Sigurdson, Alice, Singer, Christian, Slager, Susan, Soucy, Penny, Southey, Melissa, Steinemann, Doris, Swerdlow, Anthony, Szabo, Csilla, Tchatchou, Sandrine, Teixeira, Manuel, Teo, Soo, Terry, Mary, Tessier, Daniel, TeulĂŠ, Alex, Thomassen, Mads, Tihomirova, Laima, Tischkowitz, Marc, Toland, Amanda, Tung, Nadine, Turnbull, Clare, Ouweland, Ans Van Den, Rensburg, Elizabeth Van, Berg, David Ven Den, Vijai, Joseph, Wang-Gohrke, Shan, Weitzel, Jeffrey, Whittemore, Alice, Winqvist, Robert, Wong, Tien, Wu, Anna, Drakoulis Yannoukakos, Jyh-Cherng Yu, Pharoah, Paul, Hall, Per, Chenevix-Trench, Georgia, Dunning, Alison, Simard, Jacques, Couch, Fergus, Antoniou, Antonis, Easton, Douglas, and Zheng, Wei
Subjects: body regions, endocrine system diseases, nervous system, fungi, skin and connective tissue diseases
Abstract: Associations of independent signals for breast cancer risk for BRCA1 mutation carriers. (PDF 64 kb)
Published: 2016
Full Text: View/download PDF

27. Additional file 5: Table S2. of Identification of independent association signals and putative functional variants for breast cancer risk through fine-scale mapping of the 12p11 locus

Author: Chenjie Zeng, Xingyi Guo, Jirong Long, Kuchenbaecker, Karoline, Droit, Arnaud, Michailidou, Kyriaki, Ghoussaini, Maya, Siddhartha Kar, Freeman, Adam, Hopper, John, Milne, Roger, Bolla, Manjeet, Wang, Qin, Dennis, Joe, Agata, Simona, Shahana Ahmed, AittomĂ¤Ki, Kristiina, Andrulis, Irene, Anton-Culver, Hoda, Antonenkova, Natalia, Adalgeir Arason, Arndt, Volker, Arun, Banu, Arver, Brita, Francois Bacot, Barrowdale, Daniel, Baynes, Caroline, Beeghly-Fadiel, Alicia, Benitez, Javier, Bermisheva, Marina, Blomqvist, Carl, Blot, William, Bogdanova, Natalia, Bojesen, Stig, Bonanni, Bernardo, Anne-Lise Borresen-Dale, Brand, Judith, Brauch, Hiltrud, Brennan, Paul, Brenner, Hermann, Broeks, Annegien, BrĂźning, Thomas, Burwinkel, Barbara, Buys, Saundra, Qiuyin Cai, Caldes, Trinidad, Campbell, Ian, Carpenter, Jane, Chang-Claude, Jenny, Ji-Yeob Choi, Claes, Kathleen, Clarke, Christine, Cox, Angela, Cross, Simon, Czene, Kamila, Daly, Mary, Hoya, Miguel De La, Leeneer, Kim De, Devilee, Peter, Diez, Orland, Domchek, Susan, Doody, Michele, Dorfling, Cecilia, DĂśrk, Thilo, Dos-Santos-Silva, Isabel, Dumont, Martine, Dwek, Miriam, Dworniczak, Bernd, Egan, Kathleen, Eilber, Ursula, Einbeigi, Zakaria, Ejlertsen, Bent, Ellis, Steve, Frost, Debra, Lalloo, Fiona, Fasching, Peter, Jonine Figueroa, Flyger, Henrik, Friedlander, Michael, Friedman, Eitan, Gambino, Gaetana, Yu-Tang Gao, Garber, Judy, GarcĂA-Closas, Montserrat, Gehrig, Andrea, Damiola, Francesca, Lesueur, Fabienne, Mazoyer, Sylvie, Stoppa-Lyonnet, Dominique, Giles, Graham, Godwin, Andrew, Goldgar, David, GonzĂĄlez-Neira, Anna, Greene, Mark, GuĂŠnel, Pascal, Haeberle, Lothar, Haiman, Christopher, Hallberg, Emily, Hamann, Ute, Hansen, Thomas, Hart, Steven, Hartikainen, Jaana, Hartman, Mikael, Norhashimah Hassan, Healey, Sue, Hogervorst, Frans, Senno Verhoef, Hendricks, Carolyn, Hillemanns, Peter, Hollestelle, Antoinette, Hulick, Peter, Hunter, David, Imyanitov, Evgeny, Isaacs, Claudine, Ito, Hidemi, Jakubowska, Anna, Ramunas Janavicius, Jaworska-Bieniek, Katarzyna, Jensen, Uffe, John, Esther, Beauparlant, Charles Joly, Jones, Michael, Kabisch, Maria, Daehee Kang, Karlan, Beth, Kauppila, Saila, Kerin, Michael, Khan, Sofia, Khusnutdinova, Elza, Knight, Julia, Konstantopoulou, Irene, Kraft, Peter, Kwong, Ava, Laitman, Yael, Lambrechts, Diether, Conxi Lazaro, Loic Le Marchand, Chuen Lee, Lee, Min, Lester, Jenny, Jingmei Li, Liljegren, Annelie, Lindblom, Annika, Artitaya Lophatananon, Lubinski, Jan, Mai, Phuong, Mannermaa, Arto, Manoukian, Siranoush, Margolin, Sara, Marme, Frederik, Keitaro Matsuo, McGuffog, Lesley, Meindl, Alfons, Menegaux, Florence, Montagna, Marco, Muir, Kenneth, Mulligan, Anna, Nathanson, Katherine, Neuhausen, Susan, Nevanlinna, Heli, Newcomb, Polly, Nord, Silje, Nussbaum, Robert, Offit, Kenneth, Olah, Edith, Olufunmilayo Olopade, Olswold, Curtis, Osorio, Ana, Papi, Laura, Tjoung-Won Park-Simon, Paulsson-Karlsson, Ylva, Peeters, Stephanie, Peissel, Bernard, Peterlongo, Paolo, Peto, Julian, Pfeiler, Georg, Phelan, Catherine, Nadege Presneau, Radice, Paolo, Nazneen Rahman, Ramus, Susan, Rashid, Muhammad, Rennert, Gad, Rhiem, Kerstin, Rudolph, Anja, Salani, Ritu, Suleeporn Sangrajrang, Sawyer, Elinor, Marjanka Schmidt, Schmutzler, Rita, Minouk Schoemaker, SchĂźrmann, Peter, Seynaeve, Caroline, Shen, Chen-Yang, Shrubsole, Martha, Xiao-Ou Shu, Sigurdson, Alice, Singer, Christian, Slager, Susan, Soucy, Penny, Southey, Melissa, Steinemann, Doris, Swerdlow, Anthony, Szabo, Csilla, Tchatchou, Sandrine, Teixeira, Manuel, Teo, Soo, Terry, Mary, Tessier, Daniel, TeulĂŠ, Alex, Thomassen, Mads, Tihomirova, Laima, Tischkowitz, Marc, Toland, Amanda, Tung, Nadine, Turnbull, Clare, Ouweland, Ans Van Den, Rensburg, Elizabeth Van, Berg, David Ven Den, Vijai, Joseph, Wang-Gohrke, Shan, Weitzel, Jeffrey, Whittemore, Alice, Winqvist, Robert, Wong, Tien, Wu, Anna, Drakoulis Yannoukakos, Jyh-Cherng Yu, Pharoah, Paul, Hall, Per, Chenevix-Trench, Georgia, Dunning, Alison, Simard, Jacques, Couch, Fergus, Antoniou, Antonis, Easton, Douglas, and Zheng, Wei
Subjects: ComputingMethodologies_DOCUMENTANDTEXTPROCESSING, GeneralLiterature_REFERENCE(e.g.,dictionaries,encyclopedias,glossaries)
Abstract: List of the variants that were retained for further functional annotation in European descendants. (PDF 54 kb)
Published: 2016
Full Text: View/download PDF

28. Breast cancer genetic counseling after diagnosis but before treatment: A pilot study on treatment consequences and psychological impact

Author: Eveline M. A. Bleiker, Marijke D.K. Bolhaar, Senno Verhoef, Margreet G. E. M. Ausems, Daniela E E Hahn, Marijke R. Wevers, Neil K. Aaronson, and Klinische Psychologie (Psychologie, FMG)
Subjects: Adult, medicine.medical_specialty, Psychological burden, Genetic counseling, BRCA, Decision Making, Genes, BRCA2, Breast Neoplasms, Genetic Counseling, Pilot Projects, Disease, Young Adult, Breast cancer, Patient satisfaction, Risk Factors, Surveys and Questionnaires, Internal medicine, Adaptation, Psychological, medicine, Humans, Genetic Predisposition to Disease, Genetic Testing, Rapid genetic counseling and testing, Young adult, skin and connective tissue diseases, Prophylactic bilateral mastectomy, Mastectomy, Netherlands, Medicine(all), Gynecology, business.industry, Cancer, Patient Preference, General Medicine, Middle Aged, medicine.disease, Distress, Treatment Outcome, Socioeconomic Factors, Patient Satisfaction, Mutation, Female, business, Psychosocial, Stress, Psychological
Abstract: ObjectiveFemale breast cancer patients carrying a BRCA1/2-mutation have an increased risk of second primary breast and ovarian tumors. Little is known about the psychological impact and treatment consequences of rapid genetic counseling and testing offered between breast cancer diagnosis and surgery.MethodsFemale breast cancer patients, who had received rapid genetic counseling (and optional testing) (RGC(T)) at The Netherlands Cancer Institute between 2004 and 2008, received a questionnaire in 2009.ResultsBRCA-mutations were found in 10 of the 26 participants. Six mutation-carriers (60%) had an immediate bilateral mastectomy, compared with 25% of those without a mutation. Five patients (19%) reported having frequent worries about cancer recurrence; none indicated that such worries impaired daily functioning. Six patients had clinically relevant levels of breast cancer-specific distress at the time of assessment.ConclusionThese results suggest that RGC(T) in high-risk breast cancer patients may influence surgical treatment, without causing long-term psychosocial distress in the majority.Practice implicationsThese results are important, since rapid genetic counseling and testing are expected to be offered to newly diagnosed breast cancer patients with increasing frequency in order to inform these women and their surgeons about the possible familial/hereditary nature of their disease before deciding on treatment.
Published: 2012
Full Text: View/download PDF

29. Common Genetic Variation at BARD1 Is Not Associated with Breast Cancer Risk in BRCA1 or BRCA2 Mutation Carriers

Author: Maria A. Caligo, Carol Chu, Xianshu Wang, Senno Verhoef, Joanne L. Blum, Bruno Buecher, Amanda B. Spurdle, Theo A. M. van Os, Per Karlsson, Olga M. Sinilnikova, Sue Healey, Hanne Meijers-Heijboer, Georgia Chenevix-Trench, Marinus J. Blok, Timothy R. Rebbeck, Douglas F. Easton, Mary B. Daly, Annelie Liljegren, Margaret Cook, Christina G. Selkirk, Dominique Stoppa-Lyonnet, Mieke Kriege, Nadine Tung, Muriel Belotti, Susan Peock, Fiona Lalloo, Louise Izatt, Mads Thomassen, Henry T. Lynch, Christian F. Singer, Susan M. Domchek, Margreet G. E. M. Ausems, Tomasz Byrski, Olufunmilayo I. Olopade, Noralane M. Lindor, Claudine Isaacs, Katherine L. Nathanson, Gail E. Tomlinson, Clare Oliver, Hans Ehrencrona, Anna Jakubowska, Francine Durocher, Pascal Pujol, Debra Frost, Tuomas Heikkinen, Christine Lasset, Rosemarie Davidson, Jan Lubinski, Marie Agnés Collonge-Rame, Patricia A. Ganz, Nicoline Hoogerbrugge, Fergus J. Couch, Lesley McGuffog, Matti A. Rookus, Heli Nevanlinna, Helena Jernström, Sylvie Mazoyer, Jonathan Beesley, Judy Garber, Diana Eccles, Don M. Conroy, Xiaoqing Chen, Daphne Gschwantler-Kaulich, Tomasz Huzarski, Carole Verny-Pierre, Antonis C. Antoniou, D. Gareth Evans, Louise Marquart, Juul T. Wijnen, Ros Eeles, Peter Devilee, Laure Barjhoux, Fei Wan, Anne Catharine Dressler, Susan L. Neuhausen, Jeff Weitzel, Hélène Dreyfus, Biostatistiques santé, Département biostatistiques et modélisation pour la santé et l'environnement [LBBE], Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Human Genetics, Human genetics, CCA - Oncogenesis, Genetica & Celbiologie, and RS: GROW - School for Oncology and Reproduction
Subjects: Oncology, medicine.medical_specialty, Heterozygote, [SDV.OT]Life Sciences [q-bio]/Other [q-bio.OT], endocrine system diseases, Genotype, Epidemiology, Ubiquitin-Protein Ligases, Hereditary cancer and cancer-related syndromes Genetics and epigenetic pathways of disease [ONCOL 1], Breast Neoplasms, Biology, Polymorphism, Single Nucleotide, Article, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Germline mutation, Breast cancer, Risk Factors, Internal medicine, Biomarkers, Tumor, medicine, Humans, Genetic Predisposition to Disease, skin and connective tissue diseases, Germ-Line Mutation, 030304 developmental biology, BRCA2 Protein, 0303 health sciences, Cancer prevention, Hereditary cancer and cancer-related syndromes [ONCOL 1], BRCA1 Protein, Tumor Suppressor Proteins, Haplotype, Cancer, medicine.disease, Prognosis, 3. Good health, Tumor Markers, Biological, 030220 oncology & carcinogenesis, Cancer research, Female, Breast disease, SNP array
Abstract: Background: Inherited BRCA1 and BRCA2 (BRCA1/2) mutations confer elevated breast cancer risk. Knowledge of factors that can improve breast cancer risk assessment in BRCA1/2 mutation carriers may improve personalized cancer prevention strategies. Methods: A cohort of 5,546 BRCA1 and 2,865 BRCA2 mutation carriers was used to evaluate risk of breast cancer associated with BARD1 Cys557Ser. In a second nonindependent cohort of 1,537 of BRCA1 and 839 BRCA2 mutation carriers, BARD1 haplotypes were also evaluated. Results: The BARD1 Cys557Ser variant was not significantly associated with risk of breast cancer from single SNP analysis, with a pooled effect estimate of 0.90 (95% CI: 0.71–1.15) in BRCA1 carriers and 0.87 (95% CI: 0.59–1.29) in BRCA2 carriers. Further analysis of haplotypes at BARD1 also revealed no evidence that additional common genetic variation not captured by Cys557Ser was associated with breast cancer risk. Conclusion: Evidence to date does not support a role for BARD1 variation, including the Cy557Ser variant, as a modifier of risk in BRCA1/2 mutation carriers. Impact: Interactors of BRCA1/2 have been implicated as modifiers of BRCA1/2-associated cancer risk. Our finding that BARD1 does not contribute to this risk modification may focus research on other genes that do modify BRCA1/2-associated cancer risk. Cancer Epidemiol Biomarkers Prev; 20(5); 1032–8. ©2011 AACR.
Published: 2011
Full Text: View/download PDF

30. BRCA testing of breast cancer patients: medical specialists' referral patterns, knowledge and attitudes to genetic testing

Author: Senno Verhoef, E. van Riel, E.J.T. Rutgers, Margreet G. E. M. Ausems, C C Wárlám-Rodenhuis, and Human Genetics
Subjects: Adult, Male, Health Knowledge, Attitudes, Practice, medicine.medical_specialty, Referral, Attitude of Health Personnel, Genetic counseling, Genes, BRCA2, Genes, BRCA1, Breast Neoplasms, Genetic Counseling, Breast cancer, Surveys and Questionnaires, Adjuvant therapy, medicine, Humans, Genetic Testing, Practice Patterns, Physicians', Referral and Consultation, Aged, Netherlands, Genetic testing, Response rate (survey), medicine.diagnostic_test, business.industry, Cancer, Middle Aged, medicine.disease, Distress, Oncology, Family medicine, Female, business
Abstract: This study explores knowledge about hereditary breast cancer, attitudes about BRCA testing and referral pattern to a family cancer clinic among medical specialists. A total of 92 questionnaires were completed by surgeons (38), medical oncologists (29), radiation oncologists (13) and radiologists (12). The response rate was 51%. A substantial (11-56%) proportion of medical specialists do not refer patients who meet current criteria for BRCA testing. Although questions on inheritance were less well answered, overall knowledge was good. They had a positive attitude, but were concerned about the distress DNA testing might cause to family members. The majority (75%) stated that the best time for referral is after adjuvant therapy or during follow-up, but another important determinant was the patient's wish or need (12%). Further studies are needed to gain insight into the actual referral process, while ongoing training of medical specialists about genetic aspects of breast cancer is also necessary.
Published: 2010
Full Text: View/download PDF

31. Regular surveillance for Li-fraumeni syndrome: advice, adherence and perceived benefits

Author: Marielle W. G. Ruijs, Margreet G. E. M. Ausems, T. A. M. van Os, Tanja Nagtegaal, Neil K. Aaronson, Annemieke Cats, Annette H. J. T. Vriends, Senno Verhoef, Rolf H. Sijmons, C. R. M. Lammens, E. M. A. Bleiker, Anja Wagner, Liesbeth Spruijt, E. B. Gomez Garcia, Human genetics, CCA - Quality of life, Klinische Psychologie (Psychologie, FMG), Faculteit der Geneeskunde, Guided Treatment in Optimal Selected Cancer Patients (GUTS), Klinische Genetica, Genetica & Celbiologie, RS: GROW - School for Oncology and Reproduction, Clinical Genetics, and Human Genetics
Subjects: Adult, medicine.medical_specialty, Cancer Research, Family Cancer History, Cross-sectional study, MEDLINE, Psychological barriers and benefits, Article, Li-Fraumeni syndrome (LFS), FAMILIES, Li-Fraumeni Syndrome, Breast cancer, SDG 3 - Good Health and Well-being, Surveys and Questionnaires, Epidemiology, medicine, Genetics, Humans, BREAST-CANCER, Genetics(clinical), Genetics (clinical), Early Detection of Cancer, Germ-Line Mutation, PSYCHOLOGICAL DISTRESS, Gynecology, RISK, Surveillance, Hereditary cancer and cancer-related syndromes [ONCOL 1], business.industry, Cancer, P53 MUTATIONS, NONPOLYPOSIS COLORECTAL-CANCER, Middle Aged, medicine.disease, Genes, p53, Distress, Cross-Sectional Studies, Oncology, Li–Fraumeni syndrome, Li-Fraumeni syndrome (LFS) Surveillance Compliance Psychological barriers and benefits nonpolyposis colorectal-cancer breast-cancer psychological distress p53 mutations families risk, Family medicine, Patient Compliance, Female, business, Stress, Psychological, Compliance
Abstract: Contains fulltext : 89461.pdf (Publisher’s version ) (Closed access) Li Fraumeni Syndrome (LFS) is a hereditary cancer syndrome characterized by a high risk of developing various types of cancer from birth through late adulthood. Clinical benefits of surveillance for LFS are limited. The aim of this study is to investigate which advice for regular surveillance, if any, is given to high risk LFS individuals, adherence to that advice, and any psychological gain or burden derived from surveillance. Fifty-five high risk individuals (proven carriers and those at 50% risk) from families with a p53 germline mutation were invited to participate, of whom 82% completed a self-report questionnaire assessing advice for regular surveillance, compliance, perceived benefits and barriers of screening and LFS-related distress (IES) and worries (CWS). In total, 71% of the high risk family members received advice to undergo regular surveillance for LFS. The majority (78%) reported adherence with the recommended advice. All high risk women aged 25 or older reported having been advised to undergo annual breast cancer surveillance (n = 11), of whom 64% (n = 7) in specific received advice to undergo a mammography. Seventy-eight percent of respondents indicated having received tailored surveillance advice based on family cancer history. The large majority of respondents believed in the value of surveillance to detect tumors at an early stage (90%) and reported that it gave them a sense of control (84%) and security (70%). Despite its limited clinical benefits, the majority of high risk LFS family are advised to undergo, and are adherent to, and report psychological benefit from, regular surveillance programs. 01 december 2010
Published: 2010
Full Text: View/download PDF

32. Physical activity and the risk of breast cancer in BRCA1/2 mutation carriers

Author: Senno Verhoef, Christi J. van Asperen, Charlotte J. Dommering, Peggy Manders, J. Margriet Collée, Flora E. van Leeuwen, Matti A. Rookus, Anouk Pijpe, Margreet G. E. M. Ausems, Hans F. A. Vasen, Richard M. Brohet, Encarna B. Gomez-Garcia, Laura J. van't Veer, Cora M. Aalfs, Nicoline Hoogerbrugge, Human Genetics, Department of Epidemiology, Netherlands Cancer Institute, Department of Human Genetics, Radboud University Medical Center [Nijmegen], Department of Research and Education, Spaarne hospital, Department of Clinical Genetics, Rotterdam Family Cancer Clinic, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Family Cancer Clinic, The Netherlands Foundation for the Detection of Hereditary Tumours, Department of Clinical Genetics, Leiden University Medical Center (LUMC), Department of Clinical Genetics and Human Genetics, VU University Medical Center [Amsterdam], Department of Medical Genetics, University Medical Center [Utrecht], Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA)-University of Amsterdam [Amsterdam] (UvA), Maastricht University Medical Centre (MUMC), Maastricht University [Maastricht]-Maastricht University [Maastricht], Department of Pathology, Human genetics, Epidemiology and Data Science, EMGO - Quality of care, Klinische Genetica, Genetica & Celbiologie, RS: GROW - School for Oncology and Reproduction, Clinical Genetics, and Internal Medicine
Subjects: Adult, Cancer Research, medicine.medical_specialty, Heterozygote, Genetics and epigenetic pathways of disease [NCMLS 6], Epidemiology, Population, Genes, BRCA2, Genes, BRCA1, Physical exercise, Breast Neoplasms, Molecular epidemiology [NCEBP 1], 03 medical and health sciences, 0302 clinical medicine, Breast cancer, SDG 3 - Good Health and Well-being, Risk Factors, BRCA1/2, Internal medicine, medicine, Humans, Risk factor, education, Exercise, HEBON, 030304 developmental biology, Gynecology, 0303 health sciences, education.field_of_study, Hereditary cancer and cancer-related syndromes [ONCOL 1], business.industry, Physical activity, Cancer, Retrospective cohort study, Middle Aged, medicine.disease, 3. Good health, Oncology, 030220 oncology & carcinogenesis, Mutation, Female, Breast disease, business, Cohort study
Abstract: Contains fulltext : 89737.pdf (Publisher’s version ) (Closed access) BRCA1/2 mutation carriers have a high lifetime risk of developing breast cancer. Differences in penetrance indicate that this risk may be influenced by lifestyle factors. Because physical activity is one of the few modifiable risk factors, it may provide a target to add to breast cancer prevention in this high-risk population. We examined the association between self-reported lifetime sports activity and breast cancer risk in a nationwide retrospective cohort study, including 725 carriers, of whom 218 had been diagnosed with breast cancer within 10 years prior to questionnaire completion. We found a nonsignificantly decreased risk for ever engaging in sports activity (HR = 0.84, 95%CI = 0.57-1.24). Among women who had participated in sports, a medium versus low level of intensity and duration (i.e., between 11.0 and 22.7 mean MET hours/week averaged over a lifetime) reduced the risk of breast cancer (HR = 0.59, 95%CI = 0.36-0.95); no dose-response trend was observed. For mean hours/week of sports activity, a nonsignificant trend was observed (HR(low versus never) = 0.93, 95%CI = 0.60-1.43; HR(medium versus never) = 0.81, 95%CI = 0.51-1.29; HR(high versus never) = 0.78, 95%CI = 0.48-1.29; p (trend overall) = 0.272; p (trend active women) = 0.487). For number of years of sports activity no significant associations were found. Among women active in sports before age 30, mean MET hours/week showed the strongest inverse association of all activity measures (HR(medium versus low) = 0.60, 95%CI = 0.38-0.96; HR(high versus low) = 0.58, 95%CI = 0.35-0.94; p (trend) = 0.053). Engaging in sports activity after age 30 was also inversely associated with breast cancer risk (HR = 0.63, 95%CI = 0.44-0.91). Our results indicate that sports activity may reduce the risk of breast cancer in BRCA1/2 mutation carriers. 01 februari 2010
Published: 2010
Full Text: View/download PDF

33. Molecular characterization of novel germline deletions affecting SDHD and SDHC in pheochromocytoma and paraganglioma patients

Author: Peter Devilee, Annette H. J. T. Vriends, Marjan M. Weiss, Bernadette T.J. Van Brussel, Jeroen C. Jansen, Anneliese Grimbergen, Eleonora P M Corssmit, Senno Verhoef, Frederik J. Hes, Jean-Pierre Bayley, Clinical sciences, and Medical Genetics
Subjects: Adult, Male, Cancer Research, SDHB, Endocrinology, Diabetes and Metabolism, DNA Mutational Analysis, Molecular Sequence Data, Nonsense mutation, Adrenal Gland Neoplasms, Pheochromocytoma, Biology, Paraganglioma, Exon, Endocrinology, Germline mutation, medicine, Humans, Missense mutation, Genetic Testing, Germ-Line Mutation, Genetics, Base Sequence, Chromosome Mapping, Membrane Proteins, Nucleic acid amplification technique, Middle Aged, medicine.disease, Molecular biology, Succinate Dehydrogenase, Oncology, SDHD, Nucleic Acid Amplification Techniques, Gene Deletion
Abstract: A major cause of paraganglioma and pheochromocytoma is germline mutation of the tumor suppressor genes SDHB, SDHC, and SDHD, encoding subunits of succinate dehydrogenase (SDH). While many SDH missense/nonsense mutations have been identified, few large deletions have been described. We performed multiplex ligation-dependent probe amplification deletion analysis in 126 point mutation-negative patients, and here we describe four novel deletions of SDHD and SDHC. Long-range PCR was used for the fine mapping of deletions. One patient had a 10 kb AluSg–AluSx-mediated deletion including SDHD exons 1 and 2, the entire TIMM8B gene, and deletion of exons of C11orf57. A second patient had a deletion of SDHD exons 1 and 2 and exon 1 of the TIMM8B gene. A third patient showed a deletion of exon 2 of SDHD, together with a 235 bp MIRb–Tensin gene insertion. In a fourth patient, a deletion of exons 5 and 6 of the SDHC gene was found, only the second SDHC deletion currently known. The deletions of the TIMM8B and C11orf57 genes are the first to be described, but do not appear to result in an additional phenotype in these patients. Four of the eight breakpoints occurred in Alu sequences and all three SDHD deletions showed an intron 2 breakpoint. This study underlines the fact that clinically relevant deletions may encompass neighboring genes, with the potential to modify phenotype. Gene deletions of SDHD and SDHC represent a substantial proportion of all mutations, and must be considered in paraganglioma patients shown to be negative for mutations by sequencing.
Published: 2009
Full Text: View/download PDF

34. Effects of lycopene on the insulin-like growth factor (IGF) system in premenopausal breast cancer survivors and women at high familial breast cancer risk

Author: Reinie Kaas, Johannes M.G. Bonfrer, Emiel J. Th. Rutgers, Hester S. A. Oldenburg, Matti A. Rookus, Senno Verhoef, Jaap van Doorn, Nicola S. Russell, Jos H. Beijnen, Alina Vrieling, D.W. Voskuil, Laura J. van't Veer, Catharina M. Korse, Flora E. van Leeuwen, University of Groningen, and Human Genetics
Subjects: Adult, Oncology, Cancer Research, medicine.medical_specialty, Colorectal cancer, medicine.medical_treatment, Population, Medicine (miscellaneous), Breast Neoplasms, CELL-PROLIFERATION, COLORECTAL-CANCER, SUPPLEMENTATION, SERUM, Prostate cancer, Insulin-like growth factor, Lycopene, Breast cancer, Double-Blind Method, Risk Factors, Somatomedins, Internal medicine, medicine, Humans, Genetic Predisposition to Disease, Insulin-Like Growth Factor I, CAROTENOIDS, education, education.field_of_study, FACTOR-BINDING PROTEIN-3, Cross-Over Studies, Nutrition and Dietetics, business.industry, ALPHA-TOCOPHEROL, Cancer, Middle Aged, medicine.disease, FACTOR-I LEVELS, PROSTATE-CANCER, Insulin-Like Growth Factor Binding Protein 3, Endocrinology, ADIPOSE-TISSUE, Premenopause, Dietary Supplements, Population study, Female, Breast disease, business
Abstract: Insulin-like growth factor-I (IGF-I) is an important growth factor associated with increased risk of premenopausal breast cancer. We conducted a randomized, placebo-controlled, double-blind, crossover trial to evaluate whether tomato-derived lycopene supplementation (30 mg/day for 2 mo) decreases serum levels of total IGF-I in premenopausal women with 1) a history of breast cancer (n = 24) or 2) a high familial breast cancer risk (n = 36). Also, IGF binding protein (IGFBP) increasing effects were evaluated. Lycopene supplementation did not significantly alter serum total IGF-I and other IGF system components in the 2 study populations combined. However, statistically significant discordant results were observed between the 2 study populations (i.e., P
Published: 2008
Full Text: View/download PDF

35. Fine-Scale Mapping of the 4q24 Locus Identifies Two Independent Loci Associated with Breast Cancer Risk

Author: Martine Tranchant, Fergus J. Couch, Meeri Otsukka, Sabine Behrens, Jirong Long, Nadia Obi, Kamila Czene, John L. Hopper, Heather Thorne, Robert Pilarski, Anja Rudolph, Simon S. Cross, Volker Harth, Gabrielle Colleran, Hatef Darabi, Thomas Van Brussel, Eunjung Lee, Anne Lotz, E. Krol-Warmerdam, M. Pilar Zamora, Qin Wang, Andy C. H. Lee, Annie Fung, Kara Sargus, Melissa C. Southey, Katja Butterbach, Nuria Álvarez, Francois Bacot, Jeffrey G. Meyer, Ian W. Brock, Jessica Clague De Hart, Pierre Laurent-Puig, Irene L. Andrulis, Pei Chao, Arnaud Droit, Per Hall, Daniel C. Tessier, Paolo Radice, Frederic Robidoux, Don M. Conroy, Irja Erkkilä, Daniel Vincent, Antoinette Hollestelle, Christopher A. Hilker, Alicia Beeghly-Fadiel, Muhabbet Celik, Peggy Reynolds, Caroline Baynes, Sophia S. Wang, Katri Pylkäs, Kang In Nee, Robert Winqvist, Henrik Flyger, Annette Heemskerk, Sara Margolin, Hui Cai, Julie M. Cunningham, Prat Boonyawongviroj, Bernardo Bonanni, Anthony J. Swerdlow, Dan Connley, Huiyan Ma, Valerie Gaborieau, David O. Nelson, Keitaro Matsuo, Sylvie La Boissière, Pornthep Siriwanarungsan, Hidemi Ito, Ursula Eilber, Matthias W. Beckmann, Sylvia Rabstein, Natalia Bogdanova, Anna Jakubowska, Yves Raoul, Robert A.E.M. Tollenaar, Frans B. L. Hogervorst, Hannah L Park, Pierre Kerbrat, Ying Zheng, Paul D.P. Pharoah, Wanqing Wen, Judith Heinz, Annika Lindblom, Christa Stegmaier, Manjeet K. Bolla, Loris Bernard, Anna H. Wu, Alison M. Dunning, Hermann Brenner, A. Green, Thilo Dörk, Chia-Ni Hsiung, Dennis Deapen, Michael G. Schrauder, Gilian Peuteman, S.E. Higham, Sabapathy P. Balasubramanian, Irene Feroce, Christina Justenhoven, Angela Jones, William J. Blot, Nichola Johnson, Petra Seibold, D. Bowtell, Jiajun Shi, Wei Zheng, U Hamann, Pascal Guenel, P. Webb, Soo Hwang Teo, Daniela Zaffaroni, J. Blom, Rita K. Schmutzler, Douglas F. Easton, Yani Lu, Witold Zatonski, Phuah Sze Yee, Susan L. Neuhausen, Kenneth Muir, Sofia Khan, Daehee Kang, Silke Landrith, Helena Kemiläinen, Maggie Angelakos, Rich Pinder, Javier Benitez, Til Olchers, Senno Verhoef, Fred Schumacher, Martha J. Shrubsole, Teresa Selander, Teh Yew Ching, Christof Sohn, Patrick Arveux, Dorota M. Gertig, Saila Kauppila, Mervi Grip, Florentia Fostira, Jenny Chang-Claude, Michael Stagner, Kathleen Corthouts, Ellen Van Der Schoot, H Nevanlinna, Peter Bugert, Christian Baisch, Eija Myöhänen, Sonja Wolf, Hoda Anton-Culver, Nicola Miller, Cheng Har Yip, Neonila Szeszenia-Dabrowska, Nicholas K. Hayward, Dieter Flesch-Janys, Barbara Burwinkel, J. Molenaar, Eileen Williams, Marjanka K. Schmidt, Yon Ko, Anja Nieuwlaat, Chen-Yang Shen, Veli-Matti Kosma, Ian Tomlinson, Thérèse Truong, Amanda E. Toland, Artitaya Lophatananon, Mikael Hartman, Jonathan Beesley, Bernard Peissel, Paolo Peterlongo, Ji Yeob Choi, Craig Luccarini, Rosalind A. Eeles, Niall M. McInerney, Bernard Thienpont, Xiao-Ou Shu, Léa Héguy, Maya Ghoussaini, Sander Canisius, Wing-Yee Lo, Suleeporn Sangrajrang, Nur Aishah Taib, June Yashiki, Kirsimari Aaltonen, Louise A. Brinton, Elinor J. Sawyer, Alina Vrieling, Angela Cox, Frederik Marmé, Matthias Rübner, Graham G. Giles, Sonja Oeser, Hans Christiansen, Andrew Rowan, Ed Dicks, Andeas Schneeweiß, Catriona McLean, Antonis C. Antoniou, B. Pesch, Eveline Niedermayr, Volker Arndt, Janet E. Olson, Dominiek Smeets, Jingmei Li, Georgia Chenevix-Trench, Claire Mulot, Siranoush Manoukian, Hans Fischer, Ellen Crepin, Arto Mannermaa, Ali Amin Al Olama, Helen Cramp, Ans M.W. van den Ouweland, Olivia Fletcher, Sharon A. Windebank, Peter Hillemanns, Nayana Weerasooriya, James V. Lacey, Leslie Bernstein, Romuald Le Scodan, Giulietta Scuvera, P. Parsons, Thomas C. Putti, Elaine Ryder-Mills, Sara Benlloch, Beata Peplonska, Stig E. Bojesen, Kimberley Chua, Stefan Nickels, Nick Orr, Roger L. Milne, Tuomas Heikkinen, Christopher A. Haiman, Natalia Antonenkova, Volker Hermann, Maria Kabisch, Kenneth Offit, Julia A. Knight, Angela Maniscalco, Arja Jukkola-Vuorinen, Hartwig Ziegler, Chenjie Zeng, Jacques Simard, Pamela L. Horn-Ross, Daphne S.C. Lee, Xingyi Guo, Jan Lubinski, Michael J. Kerin, Loic Le Marchand, Sune F. Nielsen, Peter Devilee, A. De Fazio, Qiuyin Cai, Annie Turgeon, Yoon Sook-Yee, Silje Nord, Petra Bos, Hiltrud Brauch, Kyriaki Michailidou, Shivaani Mariapun, Kari Mononen, Alfons Meindl, Peter B. Kang, Siddhartha Kar, Alessandra Rossi, G. Chenevix-Trench, Diether Lambrechts, Karl von Smitten, Zsofia Kote-Jarai, Emiel J. Th. Rutgers, Chiu-Chen Tseng, Peter A. Fasching, Lesley McGuffog, Annegien Broekss, Johann H. Karstens, Montserrat Garcia-Closas, Thomas Brüning, David C. Whiteman, Judi Maskiell, Clinical Genetics, Cardiothoracic Surgery, Medical Oncology, and Obstetrics & Gynecology
Subjects: Genetic Markers, Linkage disequilibrium, Epidemiology, Locus (genetics), Genome-wide association study, Breast Neoplasms, Biology, Polymorphism, Single Nucleotide, Article, Breast cancer, SDG 3 - Good Health and Well-being, Risk Factors, medicine, Humans, Genetic Predisposition to Disease, Gene, Genetics, Molecular epidemiology, Case-control study, Chromosome Mapping, medicine.disease, Logistic Models, Oncology, Genetic marker, Genetic Loci, Case-Control Studies, Female, Chromosomes, Human, Pair 4, Genome-Wide Association Study
Abstract: Background: A recent association study identified a common variant (rs9790517) at 4q24 to be associated with breast cancer risk. Independent association signals and potential functional variants in this locus have not been explored. Methods: We conducted a fine-mapping analysis in 55,540 breast cancer cases and 51,168 controls from the Breast Cancer Association Consortium. Results: Conditional analyses identified two independent association signals among women of European ancestry, represented by rs9790517 [conditional P = 2.51 × 10−4; OR, 1.04; 95% confidence interval (CI), 1.02–1.07] and rs77928427 (P = 1.86 × 10−4; OR, 1.04; 95% CI, 1.02–1.07). Functional annotation using data from the Encyclopedia of DNA Elements (ENCODE) project revealed two putative functional variants, rs62331150 and rs73838678 in linkage disequilibrium (LD) with rs9790517 (r2 ≥ 0.90) residing in the active promoter or enhancer, respectively, of the nearest gene, TET2. Both variants are located in DNase I hypersensitivity and transcription factor–binding sites. Using data from both The Cancer Genome Atlas (TCGA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC), we showed that rs62331150 was associated with level of expression of TET2 in breast normal and tumor tissue. Conclusion: Our study identified two independent association signals at 4q24 in relation to breast cancer risk and suggested that observed association in this locus may be mediated through the regulation of TET2. Impact: Fine-mapping study with large sample size warranted for identification of independent loci for breast cancer risk. Cancer Epidemiol Biomarkers Prev; 24(11); 1680–91. ©2015 AACR.
Published: 2015

36. Evaluation of the Dutch BRCA1/2 clinical genetic center referral criteria in an unselected early breast cancer population

Author: Marjanka K. Schmidt, Flora E. van Leeuwen, Alexandra J. van den Broek, Senno Verhoef, Rob A. E. M. Tollenaar, Laura J. van't Veer, and Karen de Ruiter
Subjects: Adult, Heterozygote, medicine.medical_specialty, Referral, Genes, BRCA2, Population, Genes, BRCA1, Breast Neoplasms, Sensitivity and Specificity, Article, Young Adult, Germline mutation, Breast cancer, Internal medicine, Biomarkers, Tumor, Genetics, medicine, Humans, Genetic Testing, Family history, skin and connective tissue diseases, education, Referral and Consultation, Germ-Line Mutation, Genetics (clinical), Neoplasm Staging, Netherlands, Retrospective Studies, Genetic testing, education.field_of_study, medicine.diagnostic_test, business.industry, Reproducibility of Results, Cancer, Middle Aged, medicine.disease, Mutation, Mutation (genetic algorithm), Female, business
Abstract: In this study, we evaluated the diagnostic value of the Dutch Clinical Genetic Center (CGC) referral guidelines for BRCA1/2 mutation testing in 903 early breast cancer patients, unselected for family history, diagnosed in a cancer hospital before the age of 50 years in 1974-2002; most prevalent Dutch pathogenic BRCA1/2 mutations had been analyzed on coded DNA in a research setting. Forty-nine (5.4%) of the patients were proven to be BRCA1/2 mutation carriers. We found that 78% and 69% of BRCA1 and BRCA2 mutation carriers identified met the criteria for referral to the CGC based on age, family history and synchronous multiple tumors; reflected by a combined sensitivity of 75.5% and specificity of 63.2%. More than half of the BRCA1 mutation carriers, that is, 58% had a triple-negative tumor. The highest AUC was obtained by shifting the age at diagnosis threshold criterion from 40 to 35 years and by adding a 'triple-negative breast cancer' criterion with an age threshold of 45 years; the specificity increased to 71.2%, whereas the sensitivity remained the same; that is, a referral of fewer patients will lead to the identification of at least the same number of BRCA1/2 mutation carriers. Two-thirds of the BRCA1/2 mutation carriers identified in this research setting had been referred for counseling and testing. Our results indicate that, awaiting a possibly more extended mutation screening of all breast cancer patients, the triple-negative status of a breast cancer should be added to the CGC referral criteria.
Published: 2015

37. Late-Onset Common Cancers in a Kindred with an Arg213Gln TP53 Germline Mutation

Author: Marielle W. G. Ruijs, Roelof Pruntel, Laura van 't Veer, Daphne de Jong, Senno Verhoef, Arno Floore, Fred H. Menko, and G. Wigbout
Subjects: Adult, Heterozygote, Cancer Research, endocrine system diseases, Biology, Germline, Li-Fraumeni Syndrome, Germline mutation, Breast cancer, Neoplasms, Genetics, medicine, Humans, Missense mutation, neoplasms, Germ-Line Mutation, Genetics (clinical), Aged, Melanoma, Middle Aged, Genes, p53, medicine.disease, Human genetics, Oncology, Li–Fraumeni syndrome, Cancer research, Female, Sarcoma
Abstract: Li-Fraumeni syndrome (LFS) is an autosomal-dominant condition characterized by early-onset sarcoma, breast cancer and other specific tumour types. In most LFS kindreds germline TP53 mutations have been identified. In general, TP53 germline mutations are not associated with late-onset common cancers. We encountered a large kindred in which a wide spectrum of tumour types occurred, including melanoma, breast, ovarian, colorectal, stomach and renal cell cancer, without clear-cut early ages at onset of disease. An Arg213Gln TP53 germline mutation was detected in 12 out of 15 affected family members whereas testing for other cancer susceptibility genes in selected patients was negative. In vitro testing indicated that the specific TP53 mutation inactivates the protein transcriptionally. Our findings suggest that this TP53 germline mutation is a causative factor in this family and that specific TP53 germline mutations can be associated with relatively late-onset common cancers.
Published: 2006
Full Text: View/download PDF

38. CA125 and transvaginal ultrasound monitoring in high-risk women cannot prevent the diagnosis of advanced ovarian cancer

Author: Senno Verhoef, R. I. Olivier, M. A. C. Lubsen-Brandsma, M. van Beurden, Other Research, Obstetrics and Gynaecology, and Human Genetics
Subjects: Adult, medicine.medical_specialty, endocrine system diseases, medicine.medical_treatment, Genes, BRCA2, Population, Genes, BRCA1, Sensitivity and Specificity, Pelvis, Breast cancer, Predictive Value of Tests, Positive predicative value, Carcinoma, Humans, Medicine, Genetic Predisposition to Disease, Stage (cooking), education, Physical Examination, Pelvic examination, Germ-Line Mutation, Monitoring, Physiologic, Neoplasm Staging, Ultrasonography, Ovarian Neoplasms, Gynecology, education.field_of_study, medicine.diagnostic_test, business.industry, Obstetrics and Gynecology, Oophorectomy, Middle Aged, medicine.disease, female genital diseases and pregnancy complications, Oncology, CA-125 Antigen, Female, business, Ovarian cancer
Abstract: Objectives. The main objective of screening is to identify cases of ovarian cancer in early stages. However, screening of women in the general population is ineffective due to a failure of detecting early-stage disease and high false positive rates of CA125 and transvaginal ultrasound (TVU) monitoring. The purpose of this study is to evaluate ovarian cancer screening by means of pelvic examination, serum CA125 and TVU in a consecutive series of high-risk women. Methods. Clinical data were collected from 132 BRCA1, 20 BRCA2 germ line mutation carriers, 72 members of hereditary breast and ovarian cancer (HBOC) families and 88 breast cancer patients from a hereditary breast cancer (HBC) family, seen between January 1996 and December 2002. Results. Among 10 women with an elevated CA125 level and a positive TVU, three screening carcinomas (one FIGO stage IC, one stage IIIB and one stage IV) and one interval carcinoma (stage IV) were detected. Five occult ovarian/fallopian tube carcinomas (two stage IA, one stage IC, one stage IIIB and one stage IV) after bilateral prophylactic (salpingo-) oophorectomy (BP(S)O) have been found in 152 women. The sensitivity, specificity, positive and negative predictive values (PPV and NPV) of the combination of CA125 and TVU were the highest (40%, 99%, 40% and 99%) followed by CA125 alone (50%, 96%, 13% and 99%), pelvic exam (40%, 98%, 21% and 99%) and TVU, separately (40%, 90%, 6% and 99%). Conclusion. By combining CA125 with TVU results, a PPV of 40% was achieved. However, the diagnostic tools appear to be only sensitive in detecting ovarian cancer at an advanced stage, while three of four tumors with early-stage disease in this series had normal screening tests prior to the diagnosis.
Published: 2006
Full Text: View/download PDF

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

Author: Rongxi Yang, Hoda Anton-Culver, Dieter Flesch-Janys, Veli-Matti Kosma, Alexander Miron, Siranoush Manoukian, Giulietta Scuvera, Sten Cornelissen, Fergus J. Couch, Beth Y. Karlan, Janet E. Olson, Katarzyna Durda, Muhammad Usman Rashid, Diana Eccles, Debra Frost, Antonis C. Antoniou, William J. Tapper, José Ignacio Arias, Madeleine M. A. Tilanus-Linthorst, Ute Hamann, Sara Margolin, Thilo Dörk, Pilar Zamora, Sune F. Nielsen, Laura Papi, Radka Platte, Fabio Capra, Marjanka K. Schmidt, Matthias W. Beckmann, Peter A. Fasching, Tjoung Won Park-Simon, Lesley McGuffog, Alfons Meindl, Amanda B. Spurdle, Barbara Wappenschmidt, Katherine L. Nathanson, Bernardo Bonanni, Christine L. Clarke, Julian Adlard, Fiona M. Blows, Arja Jukkola-Vuorinen, Isabel dos-Santos-Silva, Catriona McLean, Georgia Chenevix-Trench, Frederique Mariette, Malcolm W.R. Reed, Douglas F. Easton, Vesa Kataja, Frederik Marmé, Laura Baglietto, Christopher A. Haiman, Monica Barile, Uffe Birk Jensen, Thomas Brüning, Shan Wang-Gohrke, Thomas Rüdiger, Paolo Radice, Alessandra Viel, Annegien Broeks, Dee W. West, Loic Le Marchand, Mary Beth Terry, Jenny Chang-Claude, Lorraine Durcan, Raymonda Varon-Mateeva, Brian E. Henderson, Robert A.E.M. Tollenaar, Hansjoerg Plendl, Katri Pylkäs, Jane Carpenter, Mads Thomassen, Kenneth Offitt, Sabine Preisler-Adams, Dennis J. Slamon, Kamila Czene, D. Gareth Evans, Senno Verhoef, Jonine Figueroa, Anja Rudolph, Kristiina Aittomäki, Arto Mannermaa, Eric Hahnen, Jacek Gronwald, Aida Karina Dieffenbach, Johanna Rantala, Ruth Swann, Paolo Peterlongo, Melissa C. Southey, Liliana Varesco, Katarzyna Jaworska-Bieniek, Elena Provenzano, Henrik Flyger, Hiltrud Brauch, Trevor Cole, Alison M. Dunning, Sue Healey, Robert Winqvist, Soo Hwang Teo, Rachel E. Factor, Timothy R. Rebbeck, Jaana M. Hartikainen, Irene L. Andrulis, Louise Jones, Rosemary L. Balleine, Gord Glendon, Doris Steinemann, David E. Goldgar, Anna Jakubowska, Paul D.P. Pharoah, Miriam Dwek, Heli Nevanlinna, Karin Kast, Nichola Johnson, Stefano Fortuzzi, Argyrios Ziogas, John W.M. Martens, Christa Stegmaier, Vernon S. Pankratz, Peter Devilee, Thomas Hansen, Christian Sutter, Vijai Joseph, Ana Osorio, Harald Surovy, Päivi Heikkilä, Kerstin Rhiem, Fredrick R. Schumacher, Susan L. Neuhausen, Michael T. Parsons, Jolanta Lissowska, Stig E. Bojesen, Jo Perkins, Christi J. van Asperen, Simon S. Cross, Susan M. Domchek, Alice S. Whittemore, J. Margriet Collée, Trinidad Caldés, Rosemarie Davidson, Judy Garber, Nina Ditsch, Norbert Arnold, Annika Lindblom, Taru A. Muranen, Rodney J. Scott, Hans Ulrich Ulmer, Åke Borg, Qin Wang, V. Arndt, Christoph Engel, Hermann Brenner, Esther M. John, Rita K. Schmutzler, Julian Peto, Jan Lubinski, Børge G. Nordestgaard, Diana Torres, Barbara Burwinkel, Natalia Bogdanova, Caroline Seynaeve, Steve Ellis, Per Hall, Daniela Zaffaroni, Peter Hillemanns, Yon Ko, Mark E. Robson, Arif B. Ekici, Roger L. Milne, Nadine Tung, Petra Seibold, Marco Montagna, Stephen J. Chanock, Louise Izatt, Andrew K. Godwin, Mervi Grip, Rohini Rau-Murthy, Anna González-Neira, Amanda E. Toland, Anna Marie Mulligan, Noralane M. Lindor, Daniel Barrowdale, Louise A. Brinton, Olivia Fletcher, Anita Bane, Dieter Niederacher, Angela Cox, Maartje J. Hooning, Barbara Pasini, Manjeet K. Bolla, Carl Blomqvist, Ros Eeles, Graham G. Giles, and Javier Benitez
Subjects: Oncology, Pathology, Cancer Research, endocrine system diseases, Receptor, ErbB-2, Genes, BRCA2, Genes, BRCA1, Triple Negative Breast Neoplasms, Tumor Status, ErbB-2, Medizinische Fakultät, Receptors, 10. No inequality, skin and connective tissue diseases, Progesterone, Medicine(all), Likelihood Functions, Age Factors, Middle Aged, Adult, Aged, Breast Neoplasms, Carcinoma, Female, Humans, Mutation, Neoplasm Grading, Neoplasm Staging, Receptors, Estrogen, Receptors, Progesterone, 3. Good health, Mutation (genetic algorithm), Receptor, Research Article, medicine.medical_specialty, Breast cancer, Germline mutation, Internal medicine, medicine, Clinical significance, ddc:610, business.industry, Cancer, medicine.disease, BRCA1, Estrogen, BRCA2, BRCA2 Mutation Carrier, Genes, Mutation testing, business
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)). Conclusions 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. Electronic supplementary material The online version of this article (doi:10.1186/s13058-014-0474-y) contains supplementary material, which is available to authorized users.
Published: 2014
Full Text: View/download PDF

40. Comparative Genomic Hybridization Profiles in Human BRCA1 and BRCA2 Breast Tumors Highlight Differential Sets of Genomic Aberrations

Author: Erik H. van Beers, Tibor van Welsem, Lodewyk F.A. Wessels, Yunlei Li, Rogier A. Oldenburg, Peter Devilee, Cees J. Cornelisse, Senno Verhoef, Frans B.L. Hogervorst, Laura J. van't Veer, and Petra M. Nederlof
Subjects: Cancer Research, Oncology
Abstract: BRCA1 or BRCA2 germline mutations cause ∼30% of breast cancers within high-risk families. This represents 5% of total breast cancer incidence. Although BRCA1 and BRCA2 are both implicated in DNA repair and genome stability, it is unknown whether BRCA1 and BRCA2 are associated with similar or distinct diseases. In a previous study we reported that BRCA1-related breast carcinomas show a distinct genomic profile as determined by comparative genomic hybridization (CGH). We now hypothesize that, if functionally equivalent, mutations in BRCA1 and BRCA2 would result in similar genomic profiles in tumors. Here we report the chromosomal gains and losses as measured by CGH in 25 BRCA2-associated breast tumors and compared them with our existing 36 BRCA1 and 30 control profiles. We compared all chromosomal regions and determined the regions of differential gain or loss between tumor classes and controls. BRCA2 and control tumors have very similar genomic profiles. As a consequence, and in contrast to BRCA1-associated tumors, CGH profiles from BRCA2-associated tumors could not be distinguished from control tumors using the classification methodology as we have developed before. The largest number of significant differences existed between BRCA1 and controls, followed by BRCA1 compared with BRCA2, suggesting different tumor development pathways for BRCA1 and BRCA2.
Published: 2005
Full Text: View/download PDF

41. Breast and ovarian cancer risks in a large series of clinically ascertained families with a high proportion of BRCA1 and BRCA2 Dutch founder mutations

Author: Douglas F. Easton, Hanne Meijers-Heijboer, Laura J. van't Veer, Christi J. van Asperen, Frans B. L. Hogervorst, Jan C. Oosterwijk, Matti A. Rookus, Richard M. Brohet, Encarna B. Gomez Garcia, Caroline Seynaeve, Margreet G. E. M. Ausems, Hebon Resource, Nicoline Hoogerbrugge, Antonis C. Antoniou, Maria E. Velthuizen, Peter Devilee, Margriet Collée, Flora E. van Leeuwen, Senno Verhoef, Fred H. Menko, Clinical Genetics, Medical Oncology, Damage and Repair in Cancer Development and Cancer Treatment (DARE), Targeted Gynaecologic Oncology (TARGON), Klinische Genetica, RS: GROW - Developmental Biology, RS: GROW - R4 - Reproductive and Perinatal Medicine, CCA -Cancer Center Amsterdam, ARD - Amsterdam Reproduction and Development, Human Genetics, Human genetics, and CCA - Oncogenesis
Subjects: Oncology, endocrine system diseases, Genes, BRCA2, Genes, BRCA1, Cohort Studies, Tumours of the digestive tract Radboud Institute for Molecular Life Sciences [Radboudumc 14], Family history, POSITION, Age of Onset, skin and connective tissue diseases, Genetics (clinical), GENOMIC DELETIONS, POPULATION, Netherlands, Genetics, education.field_of_study, CUMULATIVE RISK, GERMLINE MUTATIONS, Middle Aged, CARRIERS, Penetrance, Founder Effect, PREVALENCE, Pedigree, SUSCEPTIBILITY GENE, Hereditary Breast and Ovarian Cancer Syndrome, Female, Cohort study, Adult, Risk, medicine.medical_specialty, PENETRANCE, Population, Biology, Young Adult, Germline mutation, Breast cancer, Age Distribution, SDG 3 - Good Health and Well-being, Internal medicine, medicine, Humans, education, Aged, LINKAGE ANALYSIS, medicine.disease, Relative risk, Mutation, Ovarian cancer
Abstract: Item does not contain fulltext BACKGROUND: BRCA1 or BRCA2 mutations confer increased risks of breast and ovarian cancer, but risks have been found to vary across studies and populations. METHODS: We ascertained pedigree data of 582 BRCA1 and 176 BRCA2 families and studied the variation in breast and ovarian cancer risks using a modified segregation analysis model. RESULTS: The average cumulative breast cancer risk by age 70 years was estimated to be 45% (95% CI 36 to 52%) for BRCA1 and 27% (95% CI 14 to 38%) for BRCA2 mutation carriers. The corresponding cumulative risks for ovarian cancer were 31% (95% CI 17 to 43%) for BRCA1 and 6% (95% CI 2 to 11%) for BRCA2 mutation carriers. In BRCA1 families, breast cancer relative risk (RR) increased with more recent birth cohort (p heterogeneity = 0.0006) and stronger family histories of breast cancer (p heterogeneity < 0.001). For BRCA1, our data suggest a significant association between the location of the mutation and the ratio of breast to ovarian cancer (p
Published: 2014
Full Text: View/download PDF

42. Functional analysis of MSH2 unclassified variants found in suspected Lynch syndrome patients reveals pathogenicity due to attenuated mismatch repair

Author: Anja Wagner, Judith Prins, Arjen R. Mensenkamp, Ans M.W. van den Ouweland, Frans B. L. Hogervorst, Winand N.M. Dinjens, Liselotte P. van Hest, Marjolijn J. L. Ligtenberg, C. Marleen Kets, Rob J. Dekker, Hein te Riele, Eva A. L. Wielders, Jan Hettinger, Senno Verhoef, Fred H. Menko, Hendrikus J. Dubbink, Human genetics, CCA - Oncogenesis, Erasmus MC other, Clinical Genetics, and Pathology
Subjects: Adult, Male, medicine.medical_specialty, congenital, hereditary, and neonatal diseases and abnormalities, DNA Mutational Analysis, Molecular Sequence Data, Biology, medicine.disease_cause, DNA Mismatch Repair, Cell Line, Mice, SDG 3 - Good Health and Well-being, Molecular genetics, Genetics, medicine, Tumours of the digestive tract Radboud Institute for Molecular Life Sciences [Radboudumc 14], Animals, Humans, Missense mutation, Computer Simulation, Allele, Codon, neoplasms, Embryonic Stem Cells, Genetics (clinical), Aged, Aged, 80 and over, Mutation, Women's cancers Radboud Institute for Molecular Life Sciences [Radboudumc 17], Base Sequence, nutritional and metabolic diseases, Middle Aged, medicine.disease, Colorectal Neoplasms, Hereditary Nonpolyposis, Immunohistochemistry, Penetrance, Lynch syndrome, digestive system diseases, Pedigree, Women's cancers Radboud Institute for Health Sciences [Radboudumc 17], MutS Homolog 2 Protein, Amino Acid Substitution, MSH2, Female, DNA mismatch repair
Abstract: Item does not contain fulltext BACKGROUND: Lynch syndrome, an autosomal-dominant disorder characterised by high colorectal and endometrial cancer risks, is caused by inherited mutations in DNA mismatch repair (MMR) genes. Mutations fully abrogating gene function are unambiguously disease causing. However, missense mutations often have unknown functional implications, hampering genetic counselling. We have applied a novel approach to study three MSH2 unclassified variants (UVs) found in Dutch families with suspected Lynch syndrome. METHODS: The three mutations were recreated in the endogenous Msh2 gene in mouse embryonic stem cells by oligonucleotide-directed gene modification. The effect of the UVs on MMR activity was then tested using a set of functional assays interrogating the main MMR functions. RESULTS: We recreated and functionally tested three MSH2 UVs: MSH2-Y165D (c.493T>G), MSH2-Q690E (c.2068C>G) and MSH2-M813V (c.2437A>G). We observed reduced levels of MSH2-Y165D and MSH2-Q690E but not MSH2-M813V proteins. MSH2-M813V was able to support all MMR functions similar to wild-type MSH2, whereas MSH2-Y165D and MSH2-Q690E showed partial defects. CONCLUSIONS: Based on the results from our functional assays, we conclude that the MSH2-M813V variant is not disease causing. The MSH2-Y165D and MSH2-Q690E variants affect MMR function and are therefore likely the underlying cause of familial cancer predisposition. Since the MMR defect is partial, these variants may represent low penetrance alleles.
Published: 2014
Full Text: View/download PDF

43. Uniparental disomy with and without confined placental mosaicism: a model for trisomic zygote rescue

Author: Cardi van den Berg, Ans M.W. van den Ouweland, Frans J. Los, Dicky J. J. Halley, Diane Van Opstal, Armando P. G. Braat, Senno Verhoef, and Eveline Wesby-van Swaay
Subjects: endocrine system, education.field_of_study, medicine.medical_specialty, medicine.diagnostic_test, Obstetrics, Population, Obstetrics and Gynecology, Aneuploidy, Trisomy 16, Chorionic villus sampling, Biology, medicine.disease, Uniparental disomy, Andrology, medicine.anatomical_structure, embryonic structures, medicine, Chorionic villi, Confined placental mosaicism, education, Trisomy, reproductive and urinary physiology, Genetics (clinical)
Abstract: In the population of children born after prenatal cytogenetic investigation in chorionic villi at our department from 1992 to 1995 (N=3940), three are known to us with uniparental disomy. One case of maternal heterodisomy 16 was prenatally discovered because of trisomy 16 in direct chorionic villi with subsequently normal amniotic fluid cells. The other two had normal karyotypes in chorionic villi. Maternal heterodisomy 15 was postnatally detected in one of them because of Prader–Willi syndrome. Maternal hetero/isodisomy 16 was accidentally encountered in the other case in the course of prenatal DNA analysis of the tuberous sclerosis complex 2 region at 16p13.3. A model is presented for the understanding of the various combinations of karyotypes in direct chorionic villi, cultured chorionic villi and the fetus in the case of successful and unsuccessful trisomic zygote rescue. © 1998 John Wiley & Sons, Ltd.
Published: 1998
Full Text: View/download PDF

44. A large-scale assessment of two-way SNP interactions in breast cancer susceptibility using 46 450 cases and 42 461 controls from the breast cancer association consortium

Author: Qin Wang, Anna González-Neira, Betül T. Yesilyurt, Paolo Radice, Jenny Chang-Claude, Malcolm W.R. Reed, Graham G. Giles, Robert A.E.M. Tollenaar, Gianluca Severi, Gillian S. Dite, Fredrick R. Schumacher, J. Margriet Collée, Pascal Guénel, Fergus J. Couch, Núria Malats, Dieter Flesch-Janys, Ute Hamann, Michael J. Kerin, Asta Försti, Guillermo Pita, Christina A. Clarke, Heli Nevanlinna, Anja Rudolph, Jolanta Lissowska, Javier Benitez, Pilar Zamora, Brian E. Henderson, Elinor J. Sawyer, Arto Mannermaa, Hiltrud Brauch, Jesús Herranz, Henrik Flyger, Aida Karina Dieffenbach, Karin Leunen, Xianshu Wang, Angela Cox, Celine M. Vachon, Arif B. Ekici, Maartje J. Hooning, Antoinette Hollestelle, Volker Arndt, Hatef Darabi, Penny Soucy, Minouk J. Schoemaker, Thilo Dörk, Hoda Anton-Culver, Melissa C. Southey, Stig E. Bojesen, Yon-Dschun Ko, Natalia Bogdanova, Veli-Matti Kosma, Robert Winqvist, Argyrios Ziogas, Jingmei Li, Carmel Apicella, M. Rosario Alonso, Douglas F. Easton, Arja Jukkola-Vuorinen, Paolo Mariani, Hermann Brenner, Peter A. Fasching, Drakoulis Yannoukakos, Paolo Peterlongo, Annegien Broeks, Federik Marme, Caroline Seynaeve, Taru A. Muranen, Anna Jakubowska, Paul D.P. Pharoah, Joe Dennis, Vesa Kataja, Kamila Czene, Alison M. Dunning, Mikael Eriksson, Vessela N. Kristensen, Ian Tomlinson, Thérèse Truong, Jonathan Tyrer, Thomas Rüdiger, Montserrat Garcia-Closas, Manjeet K. Bolla, Amanda E. Toland, Thomas Brüning, John L. Hopper, kConFab Investigators, Carl Blomqvist, Lothar Häberle, Hans Ulrich Ulmer, Anna Marie Mulligan, Jan Lubinski, Diether Lambrechts, Ian W. Brock, Emiel J. Th. Rutgers, Anthony J. Swerdlow, Grethe I. Grenaker Alnæs, Stephen J. Chanock, Katarzyna Durda, Olivia Fletcher, Mervi Grip, Per Hall, Claire Mulot, Keith Humphreys, Jonine D. Figueroa, Julia A. Knight, Petra Seibold, Alan Ashworth, Laura Baglietto, Katarzyna Jaworska-Bieniek, José Ignacio Arias-Perez, Sara Margolin, Mitul Shah, Matthias W. Beckmann, Bernard Peissel, Kyriaki Michailidou, Peter Devilee, Anne Lise Børresen-Dale, Julian Peto, Georgia Chenevix-Trench, Børge G. Nordestgaard, Barbara Burwinkel, Kristiina Aittomäki, Nicola Miller, Isabel dos Santos Silva, Agnes Jager, Janet E. Olson, Roger L. Milne, Kristen S. Purrington, Jacques Simard, Irene L. Andrulis, Nick Orr, Martine Dumont, Annika Lindblom, Nichola Johnson, Marjanka K. Schmidt, Susan L. Neuhausen, Marie Sanchez, Christopher A. Haiman, Loic Le Marchand, Katri Pylkäs, Giuseppe Floris, Christa Stegmaier, Senno Verhoef, Jaana M. Hartikainen, Gord Glendon, Cancer Center Amsterdam, Oncogenomics, Clinical Genetics, and Medical Oncology
Subjects: Oncology, epistasis, Genome-wide association study, Bioinformatics, 0302 clinical medicine, Medizinische Fakultät, common variants, Genetics (clinical), risk, 0303 health sciences, Association Studies Articles, identifies 2, Family aggregation, General Medicine, Single Nucleotide, 030220 oncology & carcinogenesis, loci, alleles, Female, medicine.medical_specialty, Single-nucleotide polymorphism, Breast Neoplasms, Biology, Polymorphism, Single Nucleotide, 03 medical and health sciences, Breast cancer, SDG 3 - Good Health and Well-being, Genetic, Internal medicine, Genetics, medicine, Genetic predisposition, SNP, Humans, Genetic Predisposition to Disease, ddc:610, Allele, Polymorphism, Molecular Biology, erap1, 030304 developmental biology, Case-control study, Epistasis, Genetic, Case-Control Studies, Genome-Wide Association Study, Logistic Models, medicine.disease, confer susceptibility, genome-wide association, genetic susceptibility
Abstract: Part of the substantial unexplained familial aggregation of breast cancer may be due to interactions between common variants, but few studies have had adequate statistical power to detect interactions of realistic magnitude. We aimed to assess all two-way interactions in breast cancer susceptibility between 70 917 single nucleotide polymorphisms (SNPs) selected primarily based on prior evidence of a marginal effect. Thirty-eight international studies contributed data for 46 450 breast cancer cases and 42 461 controls of European origin as part of a multi-consortium project (COGS). First, SNPs were preselected based on evidence (P < 0.01) of a per-allele main effect, and all two-way combinations of those were evaluated by a per-allele (1 d.f.) test for interaction using logistic regression. Second, all 2.5 billion possible two-SNP combinations were evaluated using Boolean operation-based screening and testing, and SNP pairs with the strongest evidence of interaction (P < 10−4) were selected for more careful assessment by logistic regression. Under the first approach, 3277 SNPs were preselected, but an evaluation of all possible two-SNP combinations (1 d.f.) identified no interactions at P < 10−8. Results from the second analytic approach were consistent with those from the first (P > 10−10). In summary, we observed little evidence of two-way SNP interactions in breast cancer susceptibility, despite the large number of SNPs with potential marginal effects considered and the very large sample size. This finding may have important implications for risk prediction, simplifying the modelling required. Further comprehensive, large-scale genome-wide interaction studies may identify novel interacting loci if the inherent logistic and computational challenges can be overcome.
Published: 2013

45. Functional Variants at the 11q13 Risk Locus for Breast Cancer Regulate Cyclin D1 Expression through Long-Range Enhancers

Author: Yu Tang Gao, Senno Verhoef, Sofia Khan, Brian E. Henderson, M. Pilar Zamora, Roger L. Milne, Qin Wang, Jaana M. Hartikainen, Joshua A. Betts, Montserrat Garcia-Closas, Gianluca Severi, Shahana Ahmed, Katarzyna Durda, Pascal Guénel, Hidemi Ito, Manjeet K. Bolla, Francois Bacot, Gord Glendon, Hermann Brenner, Chen-Yang Shen, Suleeporn Sangrajrang, James McKay, Fergus J. Couch, Nicholas W. Knoblauch, Vernon S. Pankratz, Dieter Flesch-Janys, Henrik Flyger, Pierre Laurent-Puig, Isabel dos Santos Silva, Heiko Müller, Nichola Johnson, Alfons Meindl, Nicola Miller, Christian R. Loehberg, Mark S. Goldberg, Mikael Hartman, Daniel C. Tessier, Paolo Radice, Ann Smeets, Ute Hamann, Xueling Sim, Irene L. Andrulis, Caroline Baynes, Annika Lindblom, Craig Luccarini, Laura Baglietto, Kristiina Aittomäki, Nils Schoof, Ana-Teresa Maia, Andrew K. Godwin, David Van Den Berg, Katri Pylkäs, Caroline M. Seynaeve, Madeleine M.A. Tilanus-Linthorst, Chiu-Chen Tseng, Angela Cox, Jirong Long, Stacey L. Edwards, Kerstin B. Meyer, Daniel R. Barnes, Per Hall, Melissa C. Southey, Wei Zheng, Stig E. Bojesen, Maartje J. Hooning, Daniel Herrero, William Blot, Don M. Conroy, Alison M. Dunning, John W.M. Martens, Artitaya Lophatananon, Christopher A. Haiman, Frederik Marmé, Sabapathy P. Balasubramanian, Florence Menegaux, Peter Kraft, Sarah Stewart-Brown, Julian Peto, Volker Arndt, Kenneth Muir, Daniel Klevebring, Robert Winqvist, Jose Ignacio Arias Perez, Joe Dennis, Sune F. Nielsen, Arja Jukkola-Vuorinen, Wei Lu, Peter A. Fasching, Valerie Gaborieau, Børge G. Nordestgaard, Anthony J. Swerdlow, Mitul Shah, M. Rosario Alonso, Keitaro Matsuo, Daniel O. Stram, Hui Cai, Anja Rudolph, Arto Mannermaa, Hiroji Iwata, Matthias W. Beckmann, Eranga N. Vithana, Elinor J. Sawyer, Anna Jakubowska, Paul D.P. Pharoah, Barbara Burwinkel, Annegien Broeks, Julia A. Knight, Alan Ashworth, Diether Lambrechts, Zoe Aitken, Marjanka K. Schmidt, Peter Bailey, Catherine S. Healey, Chia-Ni Hsiung, Anna González-Neira, Lisa B. Signorello, Thilo Dörk, Keun-Young Yoo, Maya Ghoussaini, J. H. Sng, J. Margriet Collée, Sten Cornelissen, Aiko Sueta, Melissa A. Brown, Nick Orr, Peter Lichtner, Hiltrud Brauch, Douglas F. Easton, Jonine D. Figueroa, Anna H. Wu, Kristine M. Hillman, Domenico Sardella, Dong Young Noh, Minouk J. Schoemaker, Fredrick R. Schumacher, Martine Dumont, Jianjun Liu, Kyriaki Michailidou, Stephen J. Chanock, Rita K. Schmutzler, Vesa Kataja, Kamila Czene, Natalia Antonenkova, Mervi Grip, Heli Nevanlinna, Georgia Chenevix-Trench, Peter Devilee, Qiuyin Cai, Pornthep Siriwanarangsan, Jolanta Lissowska, Christine B. Ambrosone, Ian Tomlinson, Thérèse Truong, Amanda E. Toland, Anna Marie Mulligan, Jenny Chang-Claude, Kirsimari Aaltonen, John L. Hopper, Bruce A.J. Ponder, Giuseppe Floris, Christa Stegmaier, Xianshu Wang, Cheng Har Yip, Christina Justenhoven, Vessela N. Kristensen, Jingmei Li, Shou Tung Chen, Karen A. Pooley, Jonathan Tyrer, Bernardo Bonanni, Sara Margolin, Päivi Heikkilä, Keith Humphreys, Martin O'Reilly, Sandra Deming-Halverson, Thomas L. Carroll, Pei Ei Wu, Soo Hwang Teo, Hui Miao, Stéphanie Peeters, Christof Sohn, Constance Chen, Jacques Simard, Jan Lubinski, Daehee Kang, Natalia Bogdanova, Juliet D. French, Christoph Engel, Adam M. Lee, Katarzyna Jaworska-Bieniek, Drakoulis Yannoukakos, Andreas Schneeweiss, Mel Maranian, Michael J. Kerin, Loic Le Marchand, Martha J. Shrubsole, Carl Blomqvist, Char Hong Ng, Daniel Vincent, Jonathan Beesley, Paolo Peterlongo, Javier Benitez, Hoda Anton-Culver, Veli-Matti Kosma, Ed Dicks, Arif B. Ekici, Andrew H. Beck, Xiao-Ou Shu, Graham G. Giles, Stefan Nickels, Clinical Genetics, Obstetrics & Gynecology, Medical Oncology, Surgery, and Cardiothoracic Surgery
Subjects: Messenger, Electrophoretic Mobility Shift Assay, Enhancer RNAs, Genome-wide association study, Medical and Health Sciences, prostate-cancer, 0302 clinical medicine, 2.1 Biological and endogenous factors, Genetics(clinical), Cyclin D1, Aetiology, RNA, Small Interfering, Pair 11, Promoter Regions, Genetic, Luciferases, Genetics (clinical), Cancer, estrogen-receptor, Genetics & Heredity, Genetics, Regulation of gene expression, 0303 health sciences, Tumor, Silencer Elements, Reverse Transcriptase Polymerase Chain Reaction, Single Nucleotide, Biological Sciences, Chromatin, Gene Expression Regulation, Neoplastic, Enhancer Elements, Genetic, 030220 oncology & carcinogenesis, kConFab Investigators, Female, Transcriptional, GENICA Network, Human, Chromatin Immunoprecipitation, Enhancer Elements, Breast Neoplasms, GATA3 Transcription Factor, Biology, Small Interfering, Real-Time Polymerase Chain Reaction, Polymorphism, Single Nucleotide, Article, Chromosomes, Cell Line, multiple loci, Promoter Regions, 03 medical and health sciences, down-regulation, Genetic, SDG 3 - Good Health and Well-being, Cell Line, Tumor, Binding Sites, Case-Control Studies, Chromosomes, Human, Pair 11, Humans, RNA, Messenger, Silencer Elements, Transcriptional, ets-Domain Protein Elk-4, Breast Cancer, Polymorphism, Enhancer, Transcription factor, 030304 developmental biology, Neoplastic, gene-expression, susceptibility loci, growth-factor receptor-2, cell-cycle, Gene Expression Regulation, genome-wide association, Cancer research, RNA, mammary-gland, Chromatin immunoprecipitation
Abstract: Analysis of 4,405 variants in 89,050 European subjects from 41 case-control studies identified three independent association signals for estrogen-receptor-positive tumors at 11q13. The strongest signal maps to a transcriptional enhancer element in which the G allele of the best candidate causative variant rs554219 increases risk of breast cancer, reduces both binding of ELK4 transcription factor and luciferase activity in reporter assays, and may be associated with low cyclin D1 protein levels in tumors. Another candidate variant, rs78540526, lies in the same enhancer element. Risk association signal 2, rs75915166, creates a GATA3 binding site within a silencer element. Chromatin conformation studies demonstrate that these enhancer and silencer elements interact with each other and with their likely target gene, CCND1. © 2013 The American Society of Human Genetics.
Published: 2013

46. Excess breast cancer risk in first degree relatives of CHEK2*1100delC positive familial breast cancer cases

Author: John W.M. Martens, Annegien Broeks, Marjanka K. Schmidt, Rogier A. Oldenburg, Senno Verhoef, Hanne Meijers-Heijboer, Quinten Waisfisz, Maartje J. Hooning, Matti A. Rookus, Birgit I. Witte, Marianne A. Jonker, Muriel A. Adank, Clinical Genetics, Medical Oncology, Cancer Center Amsterdam, Amsterdam Reproduction & Development (AR&D), Human Genetics, Human genetics, Epidemiology and Data Science, and CCA - Oncogenesis
Subjects: Oncology, Adult, Male, Cancer Research, medicine.medical_specialty, Genotype, Population, Breast Neoplasms, Kaplan-Meier Estimate, Protein Serine-Threonine Kinases, Breast cancer, SDG 3 - Good Health and Well-being, Risk Factors, Internal medicine, Epidemiology of cancer, medicine, Humans, Family, Genetic Predisposition to Disease, First-degree relatives, education, skin and connective tissue diseases, CHEK2, Aged, Sequence Deletion, Aged, 80 and over, Family Health, education.field_of_study, business.industry, Siblings, Hazard ratio, Cancer, Middle Aged, medicine.disease, Pedigree, Checkpoint Kinase 2, Relative risk, Mutation, Female, business
Abstract: Aim The CHEK2 ∗1100delC mutation confers a relative risk of two for breast cancer (BC) in the general population. This study aims to explore the excess cancer risk due to the CHEK2 ∗1100delC mutation within a familial non- BRCA1 / 2 breast cancer setting. Patients and Methods Cancer incidences were compared between first degree relatives of 107 familial breast cancer patients positive for the CHEK2 ∗1100delC mutation ( CHEK2 positive families) and first degree relatives of 314 familial breast cancer patients without the CHEK2 ∗1100delC mutation ( CHEK2 negative families). All families were derived from the same pool of familial non- BRCA1 / 2 breast cancer families ( n = 2554). Medical information of 2188 first degree relatives of these families was analysed for cancer risk. CHEK2 ∗1100delC status of relatives was unknown. Results Increased breast cancer risk (hazard ratio (HR) 2.0 (95% confidence interval (CI): 1.4–2.7), p CHEK2 ∗1100delC positive index cases compared to sisters of CHEK2 ∗1100delC negative index cases. HR was 1.6 (95% CI: 1.0–2.4) for mothers of CHEK2 positive versus negative index cases ( p = 0.041). For second primary breast cancers HR was increased in CHEK2 ∗1100delC positive index cases (HR 2.1, 95% CI: 1.3–3.3, p = 0.003) and their sisters (HR 2.6, 95% CI: 1.1–6.1, p = 0.025). Conclusion There is an excess breast cancer risk in first degree relatives of CHEK2 ∗1100delC positive non- BRCA1 / 2 familial breast cancer patients compared to non- CHEK2 ∗1100delC familial breast cancer relatives. Genotyping for the CHEK2 ∗1100delC mutation in a familial breast cancer setting contributes to optimal clinical surveillance in countries in which this mutation is prevalent. Carriers and female relatives are eligible for stringent breast surveillance programs.
Published: 2013
Full Text: View/download PDF

47. Evidence of Gene-Environment Interactions between Common Breast Cancer Susceptibility Loci and Established Environmental Risk Factors

Author: Fergus J, Couch, Xianshu, Wang, Lesley, McGuffog, Andrew, Lee, Curtis, Olswold, Karoline B, Kuchenbaecker, Penny, Soucy, Zachary, Fredericksen, Daniel, Barrowdale, Joe, Dennis, Mia M, Gaudet, Ed, Dicks, Matthew, Kosel, Sue, Healey, Olga M, Sinilnikova, Adam, Lee, François, Bacot, Daniel, Vincent, Frans B L, Hogervorst, Susan, Peock, Dominique, Stoppa-Lyonnet, Anna, Jakubowska, Paolo, Radice, Rita Katharina, Schmutzler, Susan M, Domchek, Marion, Piedmonte, Christian F, Singer, Eitan, Friedman, Mads, Thomassen, Thomas V O, Hansen, Susan L, Neuhausen, Csilla I, Szabo, Ignacio, Blanco, Mark H, Greene, Beth Y, Karlan, Judy, Garber, Catherine M, Phelan, Jeffrey N, Weitzel, Marco, Montagna, Edith, Olah, Irene L, Andrulis, Andrew K, Godwin, Drakoulis, Yannoukakos, David E, Goldgar, Trinidad, Caldes, Heli, Nevanlinna, Ana, Osorio, Mary Beth, Terry, Mary B, Daly, Elizabeth J, van Rensburg, Ute, Hamann, Susan J, Ramus, Amanda Ewart, Toland, Maria A, Caligo, Olufunmilayo I, Olopade, Nadine, Tung, Kathleen, Claes, Mary S, Beattie, Melissa C, Southey, Evgeny N, Imyanitov, Marc, Tischkowitz, Ramunas, Janavicius, Esther M, John, Ava, Kwong, Orland, Diez, Judith, Balmaña, Rosa B, Barkardottir, Banu K, Arun, Gad, Rennert, Soo-Hwang, Teo, Patricia A, Ganz, Ian, Campbell, Annemarie H, van der Hout, Carolien H M, van Deurzen, Caroline, Seynaeve, Encarna B, Gómez Garcia, Flora E, van Leeuwen, Hanne E J, Meijers-Heijboer, Johannes J P, Gille, Margreet G E M, Ausems, Marinus J, Blok, Marjolijn J L, Ligtenberg, Matti A, Rookus, Peter, Devilee, Senno, Verhoef, Theo A M, van Os, Juul T, Wijnen, Debra, Frost, Steve, Ellis, Elena, Fineberg, Radka, Platte, D Gareth, Evans, Louise, Izatt, Rosalind A, Eeles, Julian, Adlard, Diana M, Eccles, Jackie, Cook, Carole, Brewer, Fiona, Douglas, Shirley, Hodgson, Patrick J, Morrison, Lucy E, Side, Alan, Donaldson, Catherine, Houghton, Mark T, Rogers, Huw, Dorkins, Jacqueline, Eason, Helen, Gregory, Emma, McCann, Alex, Murray, Alain, Calender, Agnès, Hardouin, Pascaline, Berthet, Capucine, Delnatte, Catherine, Nogues, Christine, Lasset, Claude, Houdayer, Dominique, Leroux, Etienne, Rouleau, Fabienne, Prieur, Francesca, Damiola, Hagay, Sobol, Isabelle, Coupier, Laurence, Venat-Bouvet, Laurent, Castera, Marion, Gauthier-Villars, Mélanie, Léoné, Pascal, Pujol, Sylvie, Mazoyer, Yves-Jean, Bignon, Elżbieta, Złowocka-Perłowska, Jacek, Gronwald, Jan, Lubinski, Katarzyna, Durda, Katarzyna, Jaworska, Tomasz, Huzarski, Amanda B, Spurdle, Alessandra, Viel, Bernard, Peissel, Bernardo, Bonanni, Giulia, Melloni, Laura, Ottini, Laura, Papi, Liliana, Varesco, Maria Grazia, Tibiletti, Paolo, Peterlongo, Sara, Volorio, Siranoush, Manoukian, Valeria, Pensotti, Norbert, Arnold, Christoph, Engel, Helmut, Deissler, Dorothea, Gadzicki, Andrea, Gehrig, Karin, Kast, Kerstin, Rhiem, Alfons, Meindl, Dieter, Niederacher, Nina, Ditsch, Hansjoerg, Plendl, Sabine, Preisler-Adams, Stefanie, Engert, Christian, Sutter, Raymonda, Varon-Mateeva, Barbara, Wappenschmidt, Bernhard H F, Weber, Brita, Arver, Marie, Stenmark-Askmalm, Niklas, Loman, Richard, Rosenquist, Zakaria, Einbeigi, Katherine L, Nathanson, Timothy R, Rebbeck, Stephanie V, Blank, David E, Cohn, Gustavo C, Rodriguez, Laurie, Small, Michael, Friedlander, Victoria L, Bae-Jump, Anneliese, Fink-Retter, Christine, Rappaport, Daphne, Gschwantler-Kaulich, Georg, Pfeiler, Muy-Kheng, Tea, Noralane M, Lindor, Bella, Kaufman, Shani, Shimon Paluch, Yael, Laitman, Anne-Bine, Skytte, Anne-Marie, Gerdes, Inge Sokilde, Pedersen, Sanne Traasdahl, Moeller, Torben A, Kruse, Uffe Birk, Jensen, Joseph, Vijai, Kara, Sarrel, Mark, Robson, Noah, Kauff, Anna Marie, Mulligan, Gord, Glendon, Hilmi, Ozcelik, Bent, Ejlertsen, Finn C, Nielsen, Lars, Jønson, Mette K, Andersen, Yuan Chun, Ding, Linda, Steele, Lenka, Foretova, Alex, Teulé, Conxi, Lazaro, Joan, Brunet, Miquel Angel, Pujana, Phuong L, Mai, Jennifer T, Loud, Christine, Walsh, Jenny, Lester, Sandra, Orsulic, Steven A, Narod, Josef, Herzog, Sharon R, Sand, Silvia, Tognazzo, Simona, Agata, Tibor, Vaszko, Joellen, Weaver, Alexandra V, Stavropoulou, Saundra S, Buys, Atocha, Romero, Miguel, de la Hoya, Kristiina, Aittomäki, Taru A, Muranen, Mercedes, Duran, Wendy K, Chung, Adriana, Lasa, Cecilia M, Dorfling, Alexander, Miron, Javier, Benitez, Leigha, Senter, Dezheng, Huo, Salina B, Chan, Anna P, Sokolenko, Jocelyne, Chiquette, Laima, Tihomirova, Tara M, Friebel, Bjarni A, Agnarsson, Karen H, Lu, Flavio, Lejbkowicz, Paul A, James, Per, Hall, Alison M, Dunning, Daniel, Tessier, Julie, Cunningham, Susan L, Slager, Chen, Wang, Steven, Hart, Kristen, Stevens, Jacques, Simard, Tomi, Pastinen, Vernon S, Pankratz, Kenneth, Offit, Douglas F, Easton, Georgia, Chenevix-Trench, and Antonis C, Antoniou
Subjects: BRCA2 Protein, Ovarian Neoplasms, Heterozygote, endocrine system diseases, Genotype, BRCA1 Protein, Breast Neoplasms, Middle Aged, Prognosis, Polymorphism, Single Nucleotide, Risk Factors, Mutation, Humans, Medicine, Female, Genetic Predisposition to Disease, skin and connective tissue diseases, Biology, Genome-Wide Association Study, Research Article
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., Author Summary BRCA1 mutation carriers have increased and variable risks of breast and ovarian cancer. To identify modifiers of breast and ovarian cancer risk in this population, a multi-stage GWAS of 14,351 BRCA1 mutation carriers was performed. Loci 1q32 and TCF7L2 at 10q25.3 were associated with breast cancer risk, and two loci at 4q32.2 and 17q21.31 were associated with ovarian cancer risk. The 4q32.3 ovarian cancer locus was not associated with ovarian cancer risk in the general population or in BRCA2 carriers and is the first indication of a BRCA1-specific risk locus for either breast or ovarian cancer. Furthermore, modeling the influence of these modifiers on cumulative risk of breast and ovarian cancer in BRCA1 mutation carriers for the first time showed that a wide range of individual absolute risks of each cancer can be estimated. These differences suggest that genetic risk modifiers may be incorporated into the clinical management of BRCA1 mutation carriers.
Published: 2012

48. Common variants at 12p11, 12q24, 9p21, 9q31.2 and in ZNF365 are associated with breast cancer risk for BRCA1 and/or BRCA2 mutation carriers

Author: Antoniou, Antonis C., Kuchenbaecker, Karoline B., Penny, Soucy, Jonathan, Beesley, Xiaoqing, Chen, Lesley, Mcguffog, Andrew, Lee, Daniel, Barrowdale, Sue, Healey, Sinilnikova, Olga M., Caligo, Maria A., Niklas, Loman, Katja, Harbst, Annika, Lindblom, Brita, Arver, Richard, Rosenquist, Per, Karlsson, Kate, Nathanson, Susan, Domchek, Tim, Rebbeck, Anna, Jakubowska, Jan, Lubinski, Katarzyna, Jaworska, Katarzyna, Durda, Zlowocka Perlowska, E., Elzbieta Złowowcka Perłowska, Ana, Osorio, Mercedes, Duran, Raquel, Andres, Javier, Benitez, Ute, Hamann, Hogervorst, Frans B., Van, A., Van Os, Theo A., Senno, Verhoef, Meijers Heijboer, Hanne E. J., Juul, Wijnen, Gomez Garcia, Encarna B., Ligtenberg, Marjolijn J., Mieke, Kriege, Margriet Collee, J., Margreet Gem Ausems, Oosterwijk, Jan C., Susan, Peock, Debra, Frost, Ellis, Steve D., Radka, Platte, Elena, Fineberg, Gareth Evans, D., Fiona, Lalloo, Chris, Jacobs, Ros, Eeles, Julian, Adlard, Rosemarie, Davidson, Trevor, Cole, Jackie, Cook, Joan, Paterson, Fiona, Douglas, Carole, Brewer, Shirley, Hodgson, Morrison, Patrick J., Lisa, Walker, Rogers, Mark T., Alan, Donaldson, Huw, Dorkins, Godwin, Andrew K., Betsy, Bove, Dominique Stoppa Lyonnet, Claude, Houdayer, Bruno, Buecher, De Pauw, A., Antoine Pauw, D. E., Sylvie, Mazoyer, Alain, Calender, Melanie, Leone, Brigitte Bressac De Paillerets, Olivier, Caron, Hagay, Sobol, Marc, Frenay, Fabienne, Prieur, Sandra, Ferrer, Isabelle, Mortemousque, Saundra, Buys, Mary, Daly, Alexander, Miron, Terry, Mb, Terry, Mu, Mary, Terry, Hopper, John L., John, Em, Esther, John M., Melissa, Southey, David, Goldgar, Singer, Christian F., Anneliese Fink Retter, Muy Kheng Tea, Geschwantler Kaulich, D., Daphne, Kaulich, Hansen, Thomas V. O., Nielsen, Finn C., Barkardottir, Rosa B., Mia, Gaudet, Tomas, Kirchhoff, Joseph, V., Joseph, Vijai, Ana Dutra Clarke, Kenneth, Offit, Marion, Piedmonte, Judy, Kirk, David, Cohn, Jean, Hurteau, John, Byron, James, Fiorica, Toland, Amanda E., Marco, Montagna, Cristina, Oliani, Evgeny, Imyanitov, Claudine, Isaacs, Laima, Tihomirova, Ignacio, Blanco, Conxi, Lazaro, Alex, Teule, Del Valle, J., Gayther, Simon A., Kunle, Odunsi, Jenny, Gross, Karlan, Beth Y., Edith, Olah, Soo Hwang Teo, Ganz, Patricia A., Beattie, Mary S., Dorfling, Cecelia M., Jansen Van Rensburg, E., Elizabeth Van Rensburg, Orland, Diez, Ava, Kwong, Schmutzler, Rita K., Barbara, Wappenschmidt, Christoph, Engel, Alfons, Meindl, Nina, Ditsch, Norbert, Arnold, Simone, Heidemann, Dieter, Niederacher, Sabine Preisler Adams, Dorothea, Gadzicki, Raymonda Varon Mateeva, Helmut, Deissler, Andrea, Gehrig, Christian, Sutter, Karin, Kast, Britta, Fiebig, Dieter, Schafer, Trinidad, Caldes, Miguel De La Hoya, Heli, Nevanlinna, Muranen, Taru A., Bernard, Lesperance, Spurdle, Amanda B., Neuhausen, Susan L., Ding, Yuan C., Xianshu, Wang, Zachary, Fredericksen, Pankratz, Vernon S., Lindor, Noralane M., Paolo, Peterlongo, Siranoush, Manoukian, Bernard, Peissel, Daniela, Zaffaroni, Bernardo, Bonanni, Loris, Bernard, Riccardo, Dolcetti, Laura, Papi, Ottini, Laura, Paolo, Radice, Greene, Mark H., Loud, Jennifer T., Andrulis, Irene L., Hilmi, Ozcelik, Anna, Mulligan, Gord, Glendon, Mads, Thomassen, Anne Marie Gerdes, Jensen, Uffe B., Anne Bine Skytte, Kruse, Torben A., Georgia Chenevix Trench, Couch, Fergus J., Jacques, Simard, Easton, Douglas F., Swedish Breast, Cancer Study S. B., Facility, Research H., Study, E., Collaborators, Study G., Investigators, K., Swe Brca Cimba, Embrace, Hebon, Study Gemo Collaborators, Kconfab, Investigators, BMC, Ed., Collaborative Oncological Gene-environment Study - COGS - - EC:FP7:HEALTH2009-05-01 - 2014-01-31 - 223175 - VALID, Centre for Cancer Genetic Epidemiology, University of Cambridge [UK] (CAM), Cancer Genomics Laboratory, Centre Hospitalier Universitaire de Québec, Genetics and Population Health Division, Queensland Institute of Medical Research, Unité Mixte de Génétique Constitutionnelle des Cancers Fréquents, Centre Léon Bérard [Lyon]-Hospices Civils de Lyon (HCL), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Section of Genetic Oncology, University of Pisa - Università di Pisa, Department of Oncology, Lund University Hospital, Department of Clinical Genetics, Karolinska University Hospital [Stockholm], Department of Genetics and Pathology, Uppsala University-Rudbeck Laboratory, Sahlgrenska University Hospital [Gothenburg], Abramson Cancer Center, University of Pennsylvania-Perelman School of Medicine, University of Pennsylvania, International Hereditary Cancer Centre-Pomeranian Medical University [Szczecin] (PUM), Postgraduate School of Molecular Medicine, Warsaw Medical University, Human Genetics Group, Spanish National Cancer Research Centre, Biomedical Research Centre Network for Rare Diseases, CIBER de Enfermedades Raras (CIBERER), Institute of Biology and Molecular Genetics, Universidad de Valladolid [Valladolid] (UVa), Medical Oncology Division, Hospital Clínico de Zaragoza, Molecular Genetics of Breast Cancer, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Family Cancer Clinic, Netherlands Cancer Institute, Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA)-University of Amsterdam [Amsterdam] (UvA), VU Medical Center, Department of Clinical Genetics and GROM, School for Oncology and Developmental Biology, Department of Human Genetics, Radboud University [Nijmegen], Erasmus University Medical Center [Rotterdam] (Erasmus MC)-Family Cancer Clinic, Department of Clinical Molecular Genetics, University Medical Center [Utrecht], Department of Genetics, VU University Medical Center [Amsterdam], Genetic Medicine, Manchester Academic Health Sciences Centre-Central Manchester University Hospitals, Clinical Genetics, Guy's and St. Thomas' NHS Foundation Trust, Oncogenetics Team, The Institute of Cancer Research-Royal Marsden NHS Foundation Trust, Yorkshire Regional Genetics Service, Ferguson-Smith Centre for Clinical Genetics, Yorkhill Hospitals, West Midlands Regional Genetics Service, Birmingham Women's and Children's NHS Foundation Trust, Sheffield Clinical Genetics Service, Sheffield Children's NHS Foundation Trust, Addenbrookes Hospital, Institute of Human Genetics, Newcastle Upon Tyne Hospitals NHS Foundation Trust, Royal Devon & Exeter Hospital, Medical Genetics Unit, University College of London [London] (UCL), Northern Ireland Regional Genetics Centre, Belfast Health and Social Care Trust, Department of Medical Genetics, Queen's University [Belfast] (QUB), Oxford Regional Genetics Service, Churchill Hospital Oxford Centre for Haematology, All Wales Medical Genetics Services, Singleton Hospital, Clinical Genetics Department, St Michael's Hospital, North West Thames Regional Genetics Service, Kennedy-Galton Centre, Department of Pathology and Laboratory Medicine, University of Kansas Medical Center [Kansas City, KS, USA], Clinical Molecular Genetics Laboratory, Fox Chase Cancer Center, Service de Génétique Oncologique, Institut Curie [Paris], Unité de génétique et biologie des cancers (U830), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de génétique, Institut Gustave Roussy (IGR), Variabilité Génétique et Maladies Humaines, Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Consultation de génétique, Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud ), Service d'Oncologie Génétique, de Prévention et Dépistage, Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Service de Génétique Clinique Chromosomique et Moléculaire, CHU Saint-Etienne, Laboratoire de Génétique Chromosomique, CH Chambéry, Service de génétique [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, Department of Internal Medicine, Huntsman Cancer Institute, Division of Population Science, Department of Cancer Biology, Dana-Farber Cancer Institute [Boston], Department of Surgery, Harvard Medical School [Boston] (HMS), Department of Epidemiology, Columbia University [New York], Centre for Molecular , Environmental, Genetic and Analytic (MEGA) Epidemiology, University of Melbourne-Centre for Molecular, Melbourne School of Population Health, Cancer Prevention Institute of California, entre for Molecular, Environmental, Genetic and Analytic (MEGA) Epidemiology, University of Melbourne, Department of Dermatology, University of Utah School of Medicine [Salt Lake City], Dept of OB/GYN and Comprehensive Cancer Center, Medizinische Universität Wien = Medical University of Vienna, Center for Genomic Medicine, Copenhagen University Hospital-Rigshospitalet [Copenhagen], Copenhagen University Hospital, Department of Pathology, University of Iceland [Reykjavik]-Landspitali - University Hospital, Epidemiology Research Program, American Cancer Society, Department of Environmental Medicine, New York University School of Medicine, NYU System (NYU)-NYU System (NYU)-NYU Cancer Institute, Clinical Genetics Service, Memorial Sloane Kettering Cancer Center [New York], Statistical and Data Center, Roswell Park Cancer Institute [Buffalo], Australia New Zealand (ANZGOG), Westmead Hospital [Sydney], Ohio State University [Columbus] (OSU), Evanston CCOP - NorthShore University Health System, University of Chicago, Southern Pines Women's Health Center, University of North Carolina [Chapel Hill] (UNC), University of North Carolina System (UNC)-University of North Carolina System (UNC), Sarasota Memorial Healthcare, Tufts Medical Center, Department of Molecular Virology, Immunology and Medical Genetics [Colombus], Ohio State University [Columbus] (OSU)-College of Medicine and Public Health [Colombus], Immunology and Molecular Oncology Unit, Istituto Oncologico Veneto IOV - IRCCS, U.O.C. di Oncologia, Laboratory of Molecular Oncology, N.N. Petrov Institute of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University [Washington] (GU), Latvian Biomedical Research and Study Centre [Rīga], Genetic Counselling Unit, IDIBELL-Catalan Institute of Oncology, Molecular Diagnostic Unit, Department of Preventive Medicine, University of Southern California (USC)-Keck School of Medicine [Los Angeles], University of Southern California (USC), Department of Gynecologic Oncology, Women's Cancer Program, Samuel Oschin Comprehensive Cancer Institute, Department of Molecular Genetics, National Institute of Oncology, Cancer Research Initiatives Foundation, Sime Darby Medical Centre-Malaysia and University Malaya Cancer Research Institute-University Malaya Medical Centre, Jonsson Comprehensive Cancer Center at UCLA, Jonsson Comprehensive Cancer Center, UCSF Cancer Risk Program, University of California (UC), Departments of Medicine, Epidemiology, and Biostatistics, UCSF, Cancer Genetics Laboratory, University of Pretoria [South Africa], Oncogenetics Laboratory, Vall d'Hebron Institute of Oncology (VHIO), The Hong Kong Hereditary Breast Cancer Family Registry, The University of Hong Kong (HKU), Department of Gynaecology and Obstetrics, University Hospital of Cologne [Cologne]-Centre of Familial Breast and Ovarian Cancer-Centre for Integrated Oncology (CIO), Institute for Medical Informatics, Statistics and Epidemiology [Leipzig] (IMISE), Universität Leipzig [Leipzig], Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), Ludwig-Maximilians-Universität München (LMU), University Hospital of Schleswig-Holstein-Christian-Albrechts-Universität zu Kiel (CAU), University Hospital Düsseldorf-Heinrich Heine Universität Düsseldorf = Heinrich Heine University [Düsseldorf], Westfälische Wilhelms-Universität Münster = University of Münster (WWU), Institute of Cell and Molecular Pathology, Hannover Medical School [Hannover] (MHH), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Universitätsklinikum Ulm - University Hospital of Ulm, Julius-Maximilians-Universität Würzburg (JMU)-Centre of Familial Breast and Ovarian Cancer, Heidelberg University Hospital [Heidelberg], University Hospital Carl Gustav Carus, Universität Regensburg (UR), University Hospital Frankfurt a.M., Molecular Oncology Laboratory, Hospital Clínico San Carlos, Department of Obstetrics and Gynecology, Helsinki University Central Hospital, Hemato-oncology service, Hôpital du Sacré-Coeur de Montréal, Department of Population Sciences, Beckman Research Institute of City of Hope, Department of Laboratory Medicine and Pathology, Mayo Clinic, Unit of Molecular Bases of Genetic Risk and Genetic Testing, Fondazione IRCCS Istituto Nazionale Tumouri (INT)-Fondazione Istituto FIRC di Oncologia Molecolare, Unit of Medical Genetics, Fondazione IRCCS Istituto Nazionale Tumouri (INT), Division of Cancer Prevention and Genetics, Department of Experimental Oncology, Istituto Europeo di Oncologia-Consortium for Genomics Technology (Cogentech), Cancer Bioimmunotherapy Unit, IRCCS-Centro di Riferimento Oncologico, Università degli Studi di Firenze = University of Florence (UniFI), Department of Molecular Medicine, Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA), Clinical Genetics Branch, National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH)-National Institutes of Health [Bethesda] (NIH), Departments of Molecular Genetics and Laboratory Medicine and Pathobiology, University of Toronto-Cancer Care Ontario, Samuel Lunenfeld Research Institute, Mount Sinai Hospital [Toronto, Canada] (MSH), Department of Laboratory Medicine and Pathobiology, University of Toronto, Department of Laboratory Medicine, St Michael's Hospital-Keenan Research Centre of the Li Ka Shing Knowledge Institute [Toronto], Ontario Cancer Genetics Network, Cancer Care Ontario, Odense University Hospital, Department of Clinical Genetics [Copenhagen], Rigshospitalet [Copenhagen], Copenhagen University Hospital-Copenhagen University Hospital, Skejby Hospital, Department of Laboratory Medicine and Pathology and Health Sciences Research, This work was supported by Cancer Research UK grants C12292/A11174 and C1287/A10118. The research leading to these results has received funding from the European Community's Seventh Framework Programme under grant agreement n° 223175 (HEALTH-F2-2009-223175), from the Canadian Institutes of Health Research for the 'CIHR Team in Familial Risks of Breast Cancer' program and by the Canadian Breast Cancer Research Alliance-grant #019511. This research was also supported by NIH grant CA128978, an NCI Specialized Program of Research Excellence (SPORE) in Breast Cancer (CA116201), a U.S. Department of Defence Ovarian Cancer Idea award (W81XWH-10-1-0341) and grants from the Breast Cancer Research Foundation and the Komen Foundation for the Cure. ACA is a CR-UK Senior Cancer Research Fellow, DFE is CR-UK Principal Research Fellow, GCT is a NHMRC Senior Principal Research Fellow, J.S. is Chairholder of the Canada Research Chair in Oncogenetics, on behalf of CIMBA, SWE-BRCA, HEBON, EMBRACE, GEMO Study Collaborators and kConFab Investigators, European Project: 223175,EC:FP7:HEALTH,FP7-HEALTH-2007-B,COGS(2009), Pediatric Surgery, Neurology, Medical Oncology, Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Roswell Park Cancer Institute [Buffalo] (RPCI), Universität Leipzig, Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Pennsylvania [Philadelphia]-Perelman School of Medicine, University of Pennsylvania [Philadelphia], Pomeranian Medical University-International Hereditary Cancer Centre, Radboud university [Nijmegen], University of Kansas Medical Center [Lawrence], Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), Georgetown University, University of California, Westfälische Wilhelms-Universität Münster (WWU), Julius-Maximilians-Universität Würzburg [Wurtzbourg, Allemagne] (JMU)-Centre of Familial Breast and Ovarian Cancer, Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI), Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], RS: GROW - School for Oncology and Reproduction, Genetica & Celbiologie, Hôpital Bretonneau-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Human Genetics, CCA -Cancer Center Amsterdam, ARD - Amsterdam Reproduction and Development, Human genetics, and CCA - Oncogenesis
Subjects: Oncology, Medicin och hälsovetenskap, Estrogen receptor, Genome-wide association study, HORMONE-RELATED PROTEIN, Chromosomes, Human, Pair 9 - genetics, Medical and Health Sciences, 0302 clinical medicine, 610 Medical sciences Medicine, CDKN2A, Risk Factors, Genotype, INVESTIGATORS, Chromosomes, Human, Pair 12 - genetics, skin and connective tissue diseases, MAMMOGRAPHIC DENSITY, Medicine(all), 0303 health sciences, BRCA1 Protein, Middle Aged, BRCA2 Protein, 3. Good health, DNA-Binding Proteins, Hereditary Breast and Ovarian Cancer Syndrome - genetics, 030220 oncology & carcinogenesis, Hereditary Breast and Ovarian Cancer Syndrome, TUMOR SUBTYPES, Female, Chromosomes, Human, Pair 9, Research Article, Adult, Breast cancer, BRCA1, BRCA2, medicine.medical_specialty, Heterozygote, SUSCEPTIBILITY LOCI, Single-nucleotide polymorphism, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, Polymorphism, Single Nucleotide, OVARIAN-CANCER, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, SDG 3 - Good Health and Well-being, Internal medicine, medicine, Humans, ddc:610, GENOME-WIDE ASSOCIATION, ddc:611, Genetic Association Studies, 030304 developmental biology, Aged, Gynecology, Chromosomes, Human, Pair 12, CONSORTIUM, BRCA1 Protein - genetics, ALLELES, medicine.disease, BRCA2 Protein - genetics, Cancer and Oncology, GENETIC MODIFIERS, Ovarian cancer, Transcription Factors
Abstract: INTRODUCTION: Several common alleles have been shown to be associated with breast and/or ovarian cancer risk for BRCA1 and BRCA2 mutation carriers. Recent genome-wide association studies of breast cancer have identified eight additional breast cancer susceptibility loci: rs1011970 (9p21, CDKN2A/B), rs10995190 (ZNF365), rs704010 (ZMIZ1), rs2380205 (10p15), rs614367 (11q13), rs1292011 (12q24), rs10771399 (12p11 near PTHLH) and rs865686 (9q31.2). METHODS: To evaluate whether these single nucleotide polymorphisms (SNPs) are associated with breast cancer risk for BRCA1 and BRCA2 carriers, we genotyped these SNPs in 12,599 BRCA1 and 7,132 BRCA2 mutation carriers and analysed the associations with breast cancer risk within a retrospective likelihood framework. RESULTS: Only SNP rs10771399 near PTHLH was associated with breast cancer risk for BRCA1 mutation carriers (per-allele hazard ratio (HR) = 0.87, 95% CI: 0.81 to 0.94, P-trend = 3 x 10-4). The association was restricted to mutations proven or predicted to lead to absence of protein expression (HR = 0.82, 95% CI: 0.74 to 0.90, P-trend = 3.1 x 10-5, P-difference = 0.03). Four SNPs were associated with the risk of breast cancer for BRCA2 mutation carriers: rs10995190, P-trend = 0.015; rs1011970, P-trend = 0.048; rs865686, 2df-P = 0.007; rs1292011 2df-P = 0.03. rs10771399 (PTHLH) was predominantly associated with estrogen receptor (ER)-negative breast cancer for BRCA1 mutation carriers (HR = 0.81, 95% CI: 0.74 to 0.90, P-trend = 4 x 10-5) and there was marginal evidence of association with ER-negative breast cancer for BRCA2 mutation carriers (HR = 0.78, 95% CI: 0.62 to 1.00, P-trend = 0.049). CONCLUSIONS: The present findings, in combination with previously identified modifiers of risk, will ultimately lead to more accurate risk prediction and an improved understanding of the disease etiology in BRCA1 and BRCA2 mutation carriers., published_or_final_version
Published: 2012
Full Text: View/download PDF

49. Refined localization of TSC1 by combined analysis of 9q34 and 16pl3 data in 14 tuberous sclerosis families

Author: Mark Nellist, Lodewijk A. Sandkuijl, Mieke N. van der Est, Senno Verhoef, Ian Daniels, Dicky J. J. Halley, Julian R. Sampson, Phillip T. Brook-Carter, Wout H. Deelen, Bart Janssen, Arjenne Hesseling, and Dick Lindhout
Subjects: Genetics, congenital, hereditary, and neonatal diseases and abnormalities, Chromosome, Chromosome 9, Locus (genetics), Biology, medicine.disease, nervous system diseases, Tuberous sclerosis, medicine.anatomical_structure, Gene mapping, Genetic linkage, hemic and lymphatic diseases, medicine, TSC1, TSC2, Genetics (clinical)
Abstract: Tuberous sclerosis (TSC) is a heterogeneous trait. Since 1990, linkage studies have yielded putative TSC loci on chromosomes 9, 11, 12 and 16. Our current analysis, performed on 14 Dutch and British families, reveals only evidence for loci on chromosome 9q34 (TSC1) and chromosome 16p13 (TSC2). We have found no indication for a third locus for TSC, linked or unlinked to either of these chromosomal regions. The majority of our families shows linkage to chromosome 9. We have refined the candidate region for TSC1 to a region of approximately 5 cM between ABL and ABO.
Published: 1994
Full Text: View/download PDF

50. Common breast cancer susceptibility loci are associated with triple-negative breast cancer

Author: Dario Greco, Gianluca Severi, Judith Heinz, Curtis Olswold, Diana Eccles, Sara Margolin, Matthias W. Beckmann, Douglas F. Easton, Thomas Dünnebier, Ian Tomlinson, Arto Mannermaa, Christine B. Ambrosone, Jo Ellen Weaver, Hans-Peter Sinn, Erik Van Limbergen, Robert Winqvist, Kristen N. Stevens, Olivia Fletcher, Rüdiger Schulz-Wendtland, Isabel dos Santos Silva, Janet E. Olson, Arif B. Ekici, Paul D.P. Pharoah, Celine M. Vachon, Stephan Nickels, Drakoulis Yannoukakos, Astrid Irwanto, Fergus J. Couch, Robert B. Diasio, Graham G. Giles, Adam M. Lee, Diether Lambrechts, S Gerty, Jonathan Beesley, Laura Baglietto, Ute Hamann, Dieter Flesch-Janys, Marjanka K. Schmidt, Harsh B. Pathak, Foluso O. Ademuyiwa, Veli-Matti Kosma, Asta Försti, Penelope Miron, Angela Cox, Arndt Hartmann, Rosemary L. Balleine, Yon Ko, William J. Tapper, Senno Verhoef, Nicholas G. Martin, Nikki Graham, Thomas Rüdiger, Fiona M. Blows, Athanasios M. Dimopoulos, Sarah-Jane Dawson, Dimitrios Pectasides, Timothy G. Lesnick, Xianshu Wang, Susan L. Slager, George Fountzilas, Heli Nevanlinna, Simon S. Cross, Grant W. Montgomery, Irene Konstantopoulou, Carl Blomqvist, Hilde Janssen, Arja Jukkola-Vuorinen, Peter A. Fasching, Jianjun Liu, Andrew K. Godwin, Hiltrud Brauch, Lorraine Durcan, Rebecca Hein, Jane Carpenter, Swati Kulkarni, Katri Pylkäs, Florentia Fostira, Jenny Chang-Claude, Zachary S. Fredericksen, Elinor J. Sawyer, Eric A. Ross, Julian Peto, and Christine L. Clarke
Subjects: Oncology, Adult, Risk, Cancer Research, medicine.medical_specialty, European Continental Ancestry Group, Genome-wide association study, Breast Neoplasms, Biology, Polymorphism, Single Nucleotide, Chromosomes, White People, Article, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Breast cancer, Internal medicine, Receptors, Epidemiology of cancer, medicine, Genetic predisposition, Humans, Genetic Predisposition to Disease, Polymorphism, Young adult, skin and connective tissue diseases, Progesterone, Triple-negative breast cancer, 030304 developmental biology, Aged, 0303 health sciences, Pair 19, Case-control study, Case-Control Studies, Chromosomes, Human, Pair 19, Female, Middle Aged, Receptors, Estrogen, Receptors, Progesterone, Single Nucleotide, medicine.disease, Estrogen, 3. Good health, TOX3, 030220 oncology & carcinogenesis, Human
Abstract: Triple-negative breast cancers are an aggressive subtype of breast cancer with poor survival, but there remains little known about the etiologic factors that promote its initiation and development. Commonly inherited breast cancer risk factors identified through genome-wide association studies display heterogeneity of effect among breast cancer subtypes as defined by the status of estrogen and progesterone receptors. In the Triple Negative Breast Cancer Consortium (TNBCC), 22 common breast cancer susceptibility variants were investigated in 2,980 Caucasian women with triple-negative breast cancer and 4,978 healthy controls. We identified six single-nucleotide polymorphisms, including rs2046210 (ESR1), rs12662670 (ESR1), rs3803662 (TOX3), rs999737 (RAD51L1), rs8170 (19p13.1), and rs8100241 (19p13.1), significantly associated with the risk of triple-negative breast cancer. Together, our results provide convincing evidence of genetic susceptibility for triple-negative breast cancer. Cancer Res; 71(19); 6240–9. ©2011 AACR.
Published: 2011

Catalog

Books, media, physical & digital resources

See catalog results

Searchworks

Select search scope, currently: Articles Catalog books, media & more in Jio Institute collections Articles journal articles & other e-resources

Search

Search Constraints

Refine your results

Search Limiters

Topic

Publication Year Range

Language

Publication Type

Journal

Database

Publisher

97 results on '"Senno Verhoef"'

Search Results

Catalog

Select search scope, currently: Articles

Catalog

books, media & more in Jio Institute collections

Articles

journal articles & other e-resources