المؤلفون: Antoniou, Antonis C., Kartsonaki, Christiana, Sinilnikova, Olga M., Soucy, Penny, McGuffog, Lesley, Healey, Sue, Lee, Andrew, Peterlongo, Paolo, Manoukian, Siranoush, Peissel, Bernard, Zaffaroni, Daniela, Cattaneo, Elisa, Barile, Monica, Pensotti, Valeria, Pasini, Barbara, Dolcetti, Riccardo, Giannini, Giuseppe, Putignano, Anna Laura, Varesco, Liliana, Radice, Paolo, Mai, Phuong L., Greene, Mark H., Andrulis, Irene L., Glendon, Gord, Ozcelik, Hilmi, Thomassen, Mads, Gerdes, Anne-Marie, Kruse, Torben A., Jensen, Uffe Birk, Crueger, Dorthe G., Caligo, Maria A., Laitman, Yael, Milgrom, Roni, Kaufman, Bella, Paluch-Shimon, Shani, Friedman, Eitan, Loman, Niklas, Harbst, Katja, Lindblom, Annika, Arver, Brita, Ehrencrona, Hans, Melin, Beatrice, Nathanson, Katherine L., Domchek, Susan M., Rebbeck, Timothy, Jakubowska, Ania, Lubinski, Jan, Gronwald, Jacek, Huzarski, Tomasz, Byrski, Tomasz, Cybulski, Cezary, Gorski, Bohdan, Osorio, Ana, Ramon y Cajal, Teresa, Fostira, Florentia, Andres, Raquel, Benitez, Javier, Hamann, Ute, Hogervorst, Frans B., Rookus, Matti A., Hooning, Maartje J., Nelen, Marcel R., van der Luijt, Rob B., van Os, Theo A. M., van Asperen, Christi J., Devilee, Peter, Meijers-Heijboer, Hanne E. J., Garcia, Encarna B. Gomez, Peock, Susan, Cook, Margaret, Frost, Debra, Platte, Radka, Leyland, Jean, Evans, D. Gareth, Lalloo, Fiona, Eeles, Ros, Izatt, Louise, Adlard, Julian, Davidson, Rosemarie, Eccles, Diana, Ong, Kai-ren, Cook, Jackie, Douglas, Fiona, Paterson, Joan, Kennedy, M. John, Miedzybrodzka, Zosia, Godwin, Andrew, Stoppa-Lyonnet, Dominique, Buecher, Bruno, Belotti, Muriel, Tirapo, Carole, Mazoyer, Sylvie, Barjhoux, Laure, Lasset, Christine, Leroux, Dominique, Faivre, Laurence, Bronner, Myriam, Prieur, Fabienne, Nogues, Catherine, Rouleau, Etienne, Pujol, Pascal, Coupier, Isabelle, Frenay, Marc, Hopper, John L., Daly, Mary B., Terry, Mary B., John, Esther M., Buys, Saundra S., Yassin, Yosuf, Miron, Alexander, Goldgar, David, Singer, Christian F., Tea, Muy-Kheng, Pfeiler, Georg, Dressler, Anne Catharina, Hansen, Thomas v. O., Jonson, Lars, Ejlertsen, Bent, Barkardottir, Rosa Bjork, Kirchhoff, Tomas, Offit, Kenneth, Piedmonte, Marion, Rodriguez, Gustavo, Small, Laurie, Boggess, John, Blank, Stephanie, Basil, Jack, Azodi, Masoud, Toland, Amanda Ewart, Montagna, Marco, Tognazzo, Silvia, Agata, Simona, Imyanitov, Evgeny, Janavicius, Ramunas, Lazaro, Conxi, Blanco, Ignacio, Pharoah, Paul D. P., Sucheston, Lara, Karlan, Beth Y., Walsh, Christine S., Olah, Edith, Bozsik, Aniko, Teo, Soo-Hwang, Seldon, Joyce L., Beattie, Mary S., van Rensburg, Elizabeth J., Sluiter, Michelle D., Diez, Orland, Schmutzler, Rita K., Wappenschmidt, Barbara, Engel, Christoph, Meindl, Alfons, Ruehl, Ina, Varon-Mateeva, Raymonda, Kast, Karin, Deissler, Helmut, Niederacher, Dieter, Arnold, Norbert, Gadzicki, Dorothea, Schoenbuchner, Ines, Caldes, Trinidad, de la Hoya, Miguel, Nevanlinna, Heli, Aittomaki, Kristiina, Dumont, Martine, Chiquette, Jocelyne, Tischkowitz, Marc, Chen, Xiaoqing, Beesley, Jonathan, Spurdle, Amanda B., Neuhausen, Susan L., Ding, Yuan Chun, Fredericksen, Zachary, Wang, Xianshu, Pankratz, Vernon S., Couch, Fergus, Simard, Jacques, Easton, Douglas F., Chenevix-Trench, Georgia, Borg, Åke, Olsson, Håkan

المصدر: Human Molecular Genetics BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation. 20(16):3304-3321

مصطلحات موضوعية: Genetic Predisposition to Disease, Female, Pair 6, Pair 1, Human, Chromosomes, Breast Neoplasms, BRCA2 Protein, BRCA1 Protein, Alleles, Adult, Aged, Heterozygote, Humans, Middle Aged, Mutation, Polymorphism, Single Nucleotide, Risk Factors, Medicin och hälsovetenskap, Medicinska och farmaceutiska grundvetenskaper, Medicinsk genetik, Medical and Health Sciences, Basic Medicine, Medical Genetics

الوصف: Two single nucleotide polymorphisms (SNPs) at 6q25.1, near the ESR1 gene, have been implicated in the susceptibility to breast cancer for Asian (rs2046210) and European women (rs9397435). A genome-wide association study in Europeans identified two further breast cancer susceptibility variants: rs11249433 at 1p11.2 and rs999737 in RAD51L1 at 14q24.1. Although previously identified breast cancer susceptibility variants have been shown to be associated with breast cancer risk for BRCA1 and BRCA2 mutation carriers, the involvement of these SNPs to breast cancer susceptibility in mutation carriers is currently unknown. To address this, we genotyped these SNPs in BRCA1 and BRCA2 mutation carriers from 42 studies from the Consortium of Investigators of Modifiers of BRCA1/2. In the analysis of 14 123 BRCA1 and 8053 BRCA2 mutation carriers of European ancestry, the 6q25.1 SNPs (r(2) = 0.14) were independently associated with the risk of breast cancer for BRCA1 mutation carriers [ hazard ratio (HR) = 1.17, 95% confidence interval (CI): 1.11-1.23, P-trend = 4.5 x 10(-9) for rs2046210; HR = 1.28, 95% CI: 1.18-1.40, P-trend = 1.3 x 10(-8) for rs9397435], but only rs9397435 was associated with the risk for BRCA2 carriers (HR = 1.14, 95% CI: 1.01-1.28, P-trend = 0.031). SNP rs11249433 (1p11.2) was associated with the risk of breast cancer for BRCA2 mutation carriers (HR = 1.09, 95% CI: 1.02-1.17, P-trend = 0.015), but was not associated with breast cancer risk for BRCA1 mutation carriers (HR = 0.97, 95% CI: 0.92-1.02, P-trend = 0.20). SNP rs999737 (RAD51L1) was not associated with breast cancer risk for either BRCA1 or BRCA2 mutation carriers (P-trend = 0.27 and 0.30, respectively). The identification of SNPs at 6q25.1 associated with breast cancer risk for BRCA1 mutation carriers will lead to a better understanding of the biology of tumour development in these women.

الوصول الحر: https://lup.lub.lu.se/record/2072146Test
http://dx.doi.org/10.1093/hmg/ddr226Test
http://www.ncbi.nlm.nih.gov/pubmed/21593217Test

المؤلفون: Urup, Thomas, Staunstrup, Line Mærsk, Michaelsen, Signe Regner, Vitting-Seerup, Kristoffer, Bennedbæk, Marc, Toft, Anders, Olsen, Lars Rønn, Jønson, Lars, Issazadeh-Navikas, Shohreh, Broholm, Helle, Hamerlik, Petra, Poulsen, Hans Skovgaard, Lassen, Ulrik Niels

المصدر: Urup , T , Staunstrup , L M , Michaelsen , S R , Vitting-Seerup , K , Bennedbæk , M , Toft , A , Olsen , L R , Jønson , L , Issazadeh-Navikas , S , Broholm , H , Hamerlik , P , Poulsen , H S & Lassen , U N 2017 , ' Transcriptional changes induced by bevacizumab combination therapy in responding and non-responding recurrent glioblastoma patients ' , BMC Cancer , vol. 17 , 278 . https://doi.org/10.1186/s12885-017-3251-3Test

مصطلحات موضوعية: Adult, Aged, Antineoplastic Agents, Bevacizumab, Brain Neoplasms, Female, Gene Expression Profiling, Glioblastoma, Humans, Male, Middle Aged, Neoplasm Recurrence, Local, Transcription, Genetic, Young Adult, Journal Article

الوصف: BACKGROUND: Bevacizumab combined with chemotherapy produces clinical durable response in 25-30% of recurrent glioblastoma patients. This group of patients has shown improved survival and quality of life. The aim of this study was to investigate changes in gene expression associated with response and resistance to bevacizumab combination therapy. METHODS: Recurrent glioblastoma patients who had biomarker-accessible tumor tissue surgically removed both before bevacizumab treatment and at time of progression were included. Patients were grouped into responders (n = 7) and non-responders (n = 14). Gene expression profiling of formalin-fixed paraffin-embedded tumor tissue was performed using RNA-sequencing. RESULTS: By comparing pretreatment samples of responders with those of non-responders no significant difference was observed. In a paired comparison analysis of pre- and posttreatment samples of non-responders 1 gene was significantly differentially expressed. In responders, this approach revealed 256 significantly differentially expressed genes (72 down- and 184 up-regulated genes at the time of progression). Genes differentially expressed in responders revealed a shift towards a more proneural and less mesenchymal phenotype at the time of progression. CONCLUSIONS: Bevacizumab combination treatment demonstrated a significant impact on the transcriptional changes in responders; but only minimal changes in non-responders. This suggests that non-responding glioblastomas progress chaotically without following distinct gene expression changes while responding tumors adaptively respond or progress by means of the same transcriptional changes. In conclusion, we hypothesize that the identified gene expression changes of responding tumors are associated to bevacizumab response or resistance mechanisms.

وصف الملف: application/pdf

الإتاحة: https://doi.org/10.1186/s12885-017-3251-3Test
https://curis.ku.dk/portal/da/publications/transcriptional-changes-induced-by-bevacizumab-combination-therapy-in-responding-and-nonresponding-recurrent-glioblastoma-patientsTest(c30823ff-2a57-4164-9b8b-c472c3e3aacd).html
https://curis.ku.dk/ws/files/183578112/Transcriptional_changes_induced_by_bevacizumab_combination_therepy.pdfTest

المؤلفون: Osorio, Ana, Milne, Roger L, Kuchenbaecker, Karoline, Vaclová, Tereza, Pita, Guillermo, Alonso, Rosario, Peterlongo, Paolo, Blanco, Ignacio, de la Hoya, Miguel, Duran, Mercedes, Díez, Orland, Ramón Y Cajal, Teresa, Konstantopoulou, Irene, Martínez-Bouzas, Cristina, Andrés Conejero, Raquel, Soucy, Penny, McGuffog, Lesley, Barrowdale, Daniel, Lee, Andrew, SWE-BRCA, Arver, Brita, Rantala, Johanna, Loman, Niklas, Ehrencrona, Hans, Olopade, Olufunmilayo I, Beattie, Mary S, Domchek, Susan M, Nathanson, Katherine, Rebbeck, Timothy R, Arun, Banu K, Karlan, Beth Y, Walsh, Christine, Lester, Jenny, John, Esther M, Whittemore, Alice S, Daly, Mary B, Southey, Melissa, Hopper, John, Terry, Mary B, Buys, Saundra S, Janavicius, Ramunas, Dorfling, Cecilia M, van Rensburg, Elizabeth J, Steele, Linda, Neuhausen, Susan L, Ding, Yuan Chun, Hansen, Thomas VO, Jønson, Lars, Ejlertsen, Bent, Gerdes, Anne-Marie, Infante, Mar, Herráez, Belén, Moreno, Leticia Thais, Weitzel, Jeffrey N, Herzog, Josef, Weeman, Kisa, Manoukian, Siranoush, Peissel, Bernard, Zaffaroni, Daniela, Scuvera, Giulietta, Bonanni, Bernardo, Mariette, Frederique, Volorio, Sara, Viel, Alessandra, Varesco, Liliana, Papi, Laura, Ottini, Laura, Tibiletti, Maria Grazia, Radice, Paolo, Yannoukakos, Drakoulis, Garber, Judy, Ellis, Steve, Frost, Debra, Platte, Radka, Fineberg, Elena, Evans, Gareth, Lalloo, Fiona, Izatt, Louise, Eeles, Ros, Adlard, Julian, Davidson, Rosemarie, Cole, Trevor, Eccles, Diana, Cook, Jackie, Hodgson, Shirley, Brewer, Carole, Tischkowitz, Marc, Douglas, Fiona, Porteous, Mary, Side, Lucy, Walker, Lisa, Morrison, Patrick, Donaldson, Alan, Kennedy, John, Foo, Claire, Godwin, Andrew K, Schmutzler, Rita Katharina, Wappenschmidt, Barbara, Rhiem, Kerstin, Engel, Christoph, Meindl, Alfons, Ditsch, Nina, Arnold, Norbert, Plendl, Hans Jörg, Niederacher, Dieter, Sutter, Christian, Wang-Gohrke, Shan, Steinemann, Doris, Preisler-Adams, Sabine, Kast, Karin, Varon-Mateeva, Raymonda, Gehrig, Andrea, Stoppa-Lyonnet, Dominique, Sinilnikova, Olga M, Mazoyer, Sylvie, Damiola, Francesca, Poppe, Bruce, Claes, Kathleen, Piedmonte, Marion, Tucker, Kathy, Backes, Floor, Rodríguez, Gustavo, Brewster, Wendy, Wakeley, Katie, Rutherford, Thomas, Caldés, Trinidad, Nevanlinna, Heli, Aittomäki, Kristiina, Rookus, Matti A, van Os, Theo AM, van der Kolk, Lizet, de Lange, JL, Meijers-Heijboer, Hanne EJ, van der Hout, AH, van Asperen, Christi J, Gómez Garcia, Encarna B, Hoogerbrugge, Nicoline, Collée, J Margriet, van Deurzen, Carolien HM, van der Luijt, Rob B, Devilee, Peter, HEBON, Olah, Edith, Lázaro, Conxi, Teulé, Alex, Menéndez, Mireia, Jakubowska, Anna, Cybulski, Cezary, Gronwald, Jacek, Lubinski, Jan, Durda, Katarzyna, Jaworska-Bieniek, Katarzyna, Johannsson, Oskar Th, Maugard, Christine, Montagna, Marco, Tognazzo, Silvia, Teixeira, Manuel R, Healey, Sue, KConFab Investigators, Olswold, Curtis, Guidugli, Lucia, Lindor, Noralane, Slager, Susan, Szabo, Csilla I, Vijai, Joseph, Robson, Mark, Kauff, Noah, Zhang, Liying, Rau-Murthy, Rohini, Fink-Retter, Anneliese, Singer, Christian F, Rappaport, Christine, Geschwantler Kaulich, Daphne, Pfeiler, Georg, Tea, Muy-Kheng, Berger, Andreas, Phelan, Catherine M, Greene, Mark H, Mai, Phuong L, Lejbkowicz, Flavio, Andrulis, Irene, Mulligan, Anna Marie, Glendon, Gord, Toland, Amanda Ewart, Bojesen, Anders, Pedersen, Inge Sokilde, Sunde, Lone, Thomassen, Mads, Kruse, Torben A, Jensen, Uffe Birk, Friedman, Eitan, Laitman, Yael, Shimon, Shani Paluch, Simard, Jacques, Easton, Douglas F, Offit, Kenneth, Couch, Fergus J, Chenevix-Trench, Georgia, Antoniou, Antonis C, Benitez, Javier

مصطلحات موضوعية: Adolescent, Adult, Aged, 80 and over, BRCA1 Protein, BRCA2 Protein, Breast Neoplasms, DNA Glycosylases, DNA Repair, Female, Genetic Predisposition to Disease, Genotype, Humans, Middle Aged, Ovarian Neoplasms, Polymorphism, Single Nucleotide, Risk

الوصف: Single Nucleotide Polymorphisms (SNPs) in genes involved in the DNA Base Excision Repair (BER) pathway could be associated with cancer risk in carriers of mutations in the high-penetrance susceptibility genes BRCA1 and BRCA2, given the relation of synthetic lethality that exists between one of the components of the BER pathway, PARP1 (poly ADP ribose polymerase), and both BRCA1 and BRCA2. In the present study, we have performed a comprehensive analysis of 18 genes involved in BER using a tagging SNP approach in a large series of BRCA1 and BRCA2 mutation carriers. 144 SNPs were analyzed in a two stage study involving 23,463 carriers from the CIMBA consortium (the Consortium of Investigators of Modifiers of BRCA1 and BRCA2). Eleven SNPs showed evidence of association with breast and/or ovarian cancer at p<0.05 in the combined analysis. Four of the five genes for which strongest evidence of association was observed were DNA glycosylases. The strongest evidence was for rs1466785 in the NEIL2 (endonuclease VIII-like 2) gene (HR: 1.09, 95% CI (1.03-1.16), p = 2.7 × 10(-3)) for association with breast cancer risk in BRCA2 mutation carriers, and rs2304277 in the OGG1 (8-guanine DNA glycosylase) gene, with ovarian cancer risk in BRCA1 mutation carriers (HR: 1.12 95%CI: 1.03-1.21, p = 4.8 × 10(-3)). DNA glycosylases involved in the first steps of the BER pathway may be associated with cancer risk in BRCA1/2 mutation carriers and should be more comprehensively studied.

وصف الملف: Electronic-eCollection; application/pdf

العلاقة: https://www.repository.cam.ac.uk/handle/1810/285112Test

الإتاحة: https://doi.org/10.17863/CAM.32483Test
https://www.repository.cam.ac.uk/handle/1810/285112Test

المؤلفون: Milne, Roger L, Kuchenbaecker, Karoline B, Vaclová, Tereza, Pita, Guillermo, Alonso, Rosario, Peterlongo, Paolo, Blanco, Ignacio, de la Hoya, Miguel, Duran, Mercedes, Díez, Orland, Ramón Y Cajal, Teresa, Konstantopoulou, Irene, Martínez-Bouzas, Cristina, Andrés Conejero, Raquel, Soucy, Penny, McGuffog, Lesley, Barrowdale, Daniel, Lee, Andrew, Arver, Brita, Rantala, Johanna, Loman, Niklas, Ehrencrona, Hans, Olopade, Olufunmilayo I, Beattie, Mary S, Domchek, Susan M, Nathanson, Katherine, Rebbeck, Timothy R, Arun, Banu K, Karlan, Beth Y, Walsh, Christine, Lester, Jenny, John, Esther M, Whittemore, Alice S, Daly, Mary B, Southey, Melissa, Hopper, John, Terry, Mary B, Buys, Saundra S, Janavicius, Ramunas, Dorfling, Cecilia M, van Rensburg, Elizabeth J, Steele, Linda, Neuhausen, Susan L, Ding, Yuan Chun, Hansen, Thomas V O, Jønson, Lars, Ejlertsen, Bent, Gerdes, Anne-Marie, Infante, Mar, Herráez, Belén, Moreno, Leticia Thais, Weitzel, Jeffrey N, Herzog, Josef, Weeman, Kisa, Manoukian, Siranoush, Peissel, Bernard, Zaffaroni, Daniela, Scuvera, Giulietta, Bonanni, Bernardo, Mariette, Frederique, Volorio, Sara, Viel, Alessandra, Varesco, Liliana, Papi, Laura, Ottini, Laura, Tibiletti, Maria Grazia, Radice, Paolo, Yannoukakos, Drakoulis, Garber, Judy, Ellis, Steve, Frost, Debra, Platte, Radka, Fineberg, Elena, Evans, Gareth, Lalloo, Fiona, Izatt, Louise, Eeles, Ros, Adlard, Julian, Davidson, Rosemarie, Cole, Trevor, Eccles, Diana, Cook, Jackie, Hodgson, Shirley, Brewer, Carole, Tischkowitz, Marc, Douglas, Fiona, Porteous, Mary, Side, Lucy, Walker, Lisa, Morrison, Patrick, Donaldson, Alan, Kennedy, John, Foo, Claire, Godwin, Andrew K, Schmutzler, Rita Katharina, Wappenschmidt, Barbara, Rhiem, Kerstin, Engel, Christoph, Meindl, Alfons, Ditsch, Nina, Arnold, Norbert, Plendl, Hans Jörg, Niederacher, Dieter, Sutter, Christian, Wang-Gohrke, Shan, Steinemann, Doris, Preisler-Adams, Sabine, Kast, Karin, Varon-Mateeva, Raymonda, Gehrig, Andrea, Stoppa-Lyonnet, Dominique, Sinilnikova, Olga M, Mazoyer, Sylvie, Damiola, Francesca, Poppe, Bruce, Claes, Kathleen, Piedmonte, Marion, Tucker, Kathy, Backes, Floor, Rodríguez, Gustavo, Brewster, Wendy, Wakeley, Katie, Rutherford, Thomas, Caldés, Trinidad, Nevanlinna, Heli, Aittomäki, Kristiina, Rookus, Matti A, van Os, Theo A M, van der Kolk, Lizet, de Lange, J L, Meijers-Heijboer, Hanne E J, van der Hout, A H, van Asperen, Christi J, Gómez Garcia, Encarna B, Hoogerbrugge, Nicoline, Collée, J Margriet, van Deurzen, Carolien H M, van der Luijt, Rob B, Devilee, Peter, Olah, Edith, Lázaro, Conxi, Teulé, Alex, Menéndez, Mireia, Jakubowska, Anna, Cybulski, Cezary, Gronwald, Jacek, Lubinski, Jan, Durda, Katarzyna, Jaworska-Bieniek, Katarzyna, Johannsson, Oskar Th, Maugard, Christine, Montagna, Marco, Tognazzo, Silvia, Teixeira, Manuel R, Healey, Sue, Olswold, Curtis, Guidugli, Lucia, Lindor, Noralane, Slager, Susan, Szabo, Csilla I, Vijai, Joseph, Robson, Mark, Kauff, Noah, Zhang, Liying, Rau-Murthy, Rohini, Fink-Retter, Anneliese, Singer, Christian F, Rappaport, Christine, Geschwantler Kaulich, Daphne, Pfeiler, Georg, Tea, Muy-Kheng, Berger, Andreas, Phelan, Catherine M, Greene, Mark H, Mai, Phuong L, Lejbkowicz, Flavio, Andrulis, Irene, Mulligan, Anna Marie, Glendon, Gord, Toland, Amanda Ewart, Bojesen, Anders, Pedersen, Inge Sokilde, Sunde, Lone, Thomassen, Mads, Kruse, Torben A, Jensen, Uffe Birk, Friedman, Eitan, Laitman, Yael, Shimon, Shani Paluch, Simard, Jacques, Easton, Douglas F, Offit, Kenneth, Couch, Fergus J, Chenevix-Trench, Georgia, Antoniou, Antonis C, Osorio, Ana, Benitez, Javier

المساهمون: Fundación Mutua Madrileña, Asociación Española Contra el Cáncer, Instituto de Salud Carlos III, Unión Europea, Cancer Research UK (Reino Unido), United States Department of Health and Human Services, Canadian Institutes of Health Research, Susan G. Komen Breast Cancer Foundation, Ralph and Marion Falk Medical Research Trust, Research Council (Lituania), University of Kansas. Cancer Center (Estados Unidos), National Institute for Health Research (Reino Unido), Deutsche Krebshilfe, Finlands Akademi (Finlandia), Dutch Cancer Society (Holanda), Dutch Research Council (Holanda), Pink Ribbons Project, Hungarian Scientific Research Fund (Hungría), Canadian Breast Cancer Network, Ministère du Développement économique, de Innovation et de Exportation (Canadá), Westat (Estados Unidos)

مصطلحات موضوعية: Adolescent, Adult, Aged, 80 and over, BRCA1 Protein, BRCA2 Protein, Breast Neoplasms, DNA Glycosylases, DNA Repair, Female, Genetic Predisposition to Disease, Genotype, Humans, Middle Aged, Ovarian Neoplasms, Polymorphism, Single Nucleotide, Risk

الوصف: Single Nucleotide Polymorphisms (SNPs) in genes involved in the DNA Base Excision Repair (BER) pathway could be associated with cancer risk in carriers of mutations in the high-penetrance susceptibility genes BRCA1 and BRCA2, given the relation of synthetic lethality that exists between one of the components of the BER pathway, PARP1 (poly ADP ribose polymerase), and both BRCA1 and BRCA2. In the present study, we have performed a comprehensive analysis of 18 genes involved in BER using a tagging SNP approach in a large series of BRCA1 and BRCA2 mutation carriers. 144 SNPs were analyzed in a two stage study involving 23,463 carriers from the CIMBA consortium (the Consortium of Investigators of Modifiers of BRCA1 and BRCA2). Eleven SNPs showed evidence of association with breast and/or ovarian cancer at p<0.05 in the combined analysis. Four of the five genes for which strongest evidence of association was observed were DNA glycosylases. The strongest evidence was for rs1466785 in the NEIL2 (endonuclease VIII-like 2) gene (HR: 1.09, 95% CI (1.03-1.16), p = 2.7 × 10(-3)) for association with breast cancer risk in BRCA2 mutation carriers, and rs2304277 in the OGG1 (8-guanine DNA glycosylase) gene, with ovarian cancer risk in BRCA1 mutation carriers (HR: 1.12 95%CI: 1.03-1.21, p = 4.8 × 10(-3)). DNA glycosylases involved in the first steps of the BER pathway may be associated with cancer risk in BRCA1/2 mutation carriers and should be more comprehensively studied. ; The CNIO study was supported by Mutua Madrilena Foundation (FMMA), Spanish Association against Cancer (AECC08), RTICC 06/0020/1060 and FISPI12/00070. Funding for the iCOGS infrastructure came from: the European Community's Seventh Framework Programme under grant agreement no 223175 (HEALTH-F2-2009-223175) (COGS), Cancer Research UK (C1287/A10118, C1287/A 10710, C12292/A11174, C5047/A8384, C5047/A15007, C5047/A10692), the National Institutes of Health (CA128978) and Post-Cancer GWAS initiative (No. 1 U19 CA 148537 - the GAME-ON initiative), the ...

العلاقة: https://doi.org/10.1371/journal.pgen.1004256Test; info:eu_repo/grantAgreement/ES/06/0020/1060; info:eu_repo/grantAgreement/ES/RD06/0020/0021; PLoS Genet . 2014 ;10(4):e1004256.; http://hdl.handle.net/20.500.12105/11412Test; PLoS genetics

الإتاحة: https://doi.org/20.500.12105/11412Test
https://doi.org/10.1371/journal.pgen.1004256Test
https://hdl.handle.net/20.500.12105/11412Test

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

المساهمون: Mayo Clin, Dept Lab Med & Pathol, Rochester, MN 55905 USA, Mayo Clin, Rochester, MN USA, Univ Cambridge, Ctr Canc Genet Epidemiol, Dept Publ Hlth & Primary Care, Cambridge, England, Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA, Ctr Hosp Univ Quebec, Canc Genom Lab, Quebec City, PQ, Canada, Univ Laval, Quebec City, PQ, Canada, Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA, Queensland Inst Med Res, Dept Genet, Brisbane, Qld 4006, Australia, Hosp Civils Lyon, Unite Mixte Genet Constitut Canc Frequents, Ctr Leon Berard, Lyon, France, Univ Lyon 1, INSERM U1052, CNRS UMR5286, Ctr Rech Cancerol Lyon, F-69365 Lyon, France, Mayo Clin, Dept Mol Pharmacol & Expt Therapeut MPET, Rochester, MN USA, Ctr Innovat Genome Quebec, Montreal, PQ, Canada, McGill Univ, Montreal, PQ, Canada, Netherlands Canc Inst, Family Canc Clin, Amsterdam, Netherlands, Inst Curie, Dept Tumour Biol, Paris, France, Inst Curie, INSERM U830, Paris, France, Univ Paris 05, Sorbonne Paris Cite, Paris, France, Pomeranian Med Univ, Dept Genet & Pathol, Szczecin, Poland, Peter MacCallum Canc Ctr, Kathleen Cuningham Consortium Res Familial Breast, Melbourne, Vic, Australia, Fdn IRCCS Ist Nazl Tumori INT, Unit Mol Bases Genet Risk & Genet Testing, Dept Prevent & Predict Med, Milan, Italy, Fdn Ist FIRC Oncol Mol, IFOM, Milan, Italy, Univ Hosp Cologne, Ctr Familial Breast & Ovarian Canc, Dept Obstet & Gynaecol, Cologne, Germany, Univ Hosp Cologne, Ctr Integrated Oncol, Ctr Mol Med Cologne, Cologne, Germany, Lund Univ, Dept Oncol, Lund, Sweden, Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA, Roswell Pk Canc Inst, Gynecol Oncol Grp, Stat & Data Ctr, Buffalo, NY 14263 USA, Med Univ Vienna, Dept Obstet & Gynecol, Vienna, Austria, Med Univ Vienna, Ctr Comprehens Canc, Vienna, Austria, Chaim Sheba Med Ctr, Tel Aviv, Israel, Odense Univ Hosp, Dept Clin Genet, DK-5000 Odense, Denmark, Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada, Copenhagen Univ Hosp, Ctr Genom Med, Rigshosp, Copenhagen, Denmark, City Hope Natl Med Ctr, Dept Populat Sci, Beckman Res Inst, Duarte, CA USA, Univ Delaware, Ctr Translat Canc Res, Dept Biol Sci, Newark, DE USA, IDIBELL Catalan Inst Oncol, Genet Counseling Unit, Hereditary Canc Program, Barcelona, Spain, IDIBGI Catalan Inst Oncol, Genet Counseling Unit, Hereditary Canc Program, Girona, Spain, IDIBELL Catalan Inst Oncol, Translat Res Lab, Breast Canc & Syst Biol Unit, Barcelona, Spain, Univ Toronto, Womens Coll Res Inst, Toronto, ON, Canada, Fox Chase Canc Ctr, Philadelphia, PA 19111 USA, Univ Utah, Sch Med, Dept Internal Med, Huntsman Canc Inst, Salt Lake City, UT USA, Univ Helsinki, Cent Hosp, Dept Clin Genet, Helsinki, Finland, Univ Valladolid IBGM UVA, Inst Biol & Mol Genet, Valladolid, Spain, Columbia Univ, Dept Pediat, New York, NY 10027 USA, Hosp Santa Creu & Sant Pau, Genet Serv, Barcelona, Spain, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA, Canc Prevent Inst Calif, Breast Canc Family Registry, Fremont, CA USA, Spanish Natl Canc Ctr CNIO, Human Genet Grp, Madrid, Spain, Spanish Natl Canc Ctr CNIO, Genotyping Unit, Madrid, Spain, Biomed Network Rare Dis CIBERER, Madrid, Spain, Ohio State Univ, Ctr Comprehens Canc, Div Human Genet, Dept Internal Med, Columbus, OH 43210 USA, Univ Calif San Francisco, Canc Risk Program, Helen Diller Family Canc Ctr, San Francisco, CA 94143 USA, Univ Quebec, Unite Rech Sante Populat, Ctr Malad Sein Deschenes Fabia, Ctr Rech FRSQ,Ctr Hosp, Quebec City, PQ, Canada, Latvian Biomed Res & Study Ctr, Riga, Latvia, Univ Penn, Philadelphia, PA 19104 USA, Landspitali Univ Hosp, Reykjavik, Iceland, Univ Iceland, Sch Med, Reykjavik, Iceland, Clalit Natl Israeli Canc Control Ctr, Haifa, Israel, Carmel Hosp, Dept Community Med & Epidemiol, Haifa, Israel, Peter MacCallum Canc Ctr, Familial Canc Ctr, Melbourne, Vic, Australia, Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden, Univ Cambridge, Ctr Canc Genet Epidemiol, Dept Oncol, Cambridge, England, McGill Univ, Dept Human Genet, Montreal, PQ, Canada, McGill Univ, Genome Quebec Innovat Ctr, Montreal, PQ, Canada

مصطلحات موضوعية: Brjóstakrabbamein, Erfðir, Gen, BRCA1 Protein, BRCA2 Protein, Breast Neoplasms, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Heterozygote, Humans, Middle Aged, Mutation, Ovarian Neoplasms, Polymorphism, Single Nucleotide, Prognosis, Risk Factors

الوصف: To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files. This article is open access. ; 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. ; IH CA128978 P30 CA033752 R01CA74415 1R01 CA149429-01 NCI Specialized Program of Research Excellence (SPORE) in Breast Cancer CA116201 U.S. ...

العلاقة: http://dx.doi.org/10.1371/journal.pgen.1003212Test; PLoS Genet. 2013, 9 (3):e1003212; http://hdl.handle.net/2336/312762Test; PLoS genetics

الإتاحة: https://doi.org/10.1371/journal.pgen.1003212Test
http://hdl.handle.net/2336/312762Test

المؤلفون: Ramus, Susan J, Kartsonaki, Christiana, Gayther, Simon A, Pharoah, Paul D P, Sinilnikova, Olga M, Beesley, Jonathan, Chen, Xiaoqing, McGuffog, Lesley, Healey, Sue, Couch, Fergus J, Wang, Xianshu, Fredericksen, Zachary, Peterlongo, Paolo, Manoukian, Siranoush, Peissel, Bernard, Zaffaroni, Daniela, Roversi, Gaia, Barile, Monica, Viel, Alessandra, Allavena, Anna, Ottini, Laura, Papi, Laura, Gismondi, Viviana, Capra, Fabio, Radice, Paolo, Greene, Mark H, Mai, Phuong L, Andrulis, Irene L, Glendon, Gord, Ozcelik, Hilmi, Thomassen, Mads, Gerdes, Anne-Marie, Kruse, Torben A, Cruger, Dorthe, Jensen, Uffe Birk, Caligo, Maria Adelaide, Olsson, Håkan, Kristoffersson, Ulf, Lindblom, Annika, Arver, Brita, Karlsson, Per, Stenmark Askmalm, Marie, Borg, Ake, Neuhausen, Susan L, Ding, Yuan Chun, Nathanson, Katherine L, Domchek, Susan M, Jakubowska, Anna, Lubiński, Jan, Huzarski, Tomasz, Byrski, Tomasz, Gronwald, Jacek, Górski, Bohdan, Cybulski, Cezary, Dębniak, Tadeusz, Osorio, Ana, Durán, Mercedes, Tejada, Maria-Isabel, Benítez, Javier, Hamann, Ute, Rookus, Matti A, Verhoef, Senno, Tilanus-Linthorst, Madeleine A, Vreeswijk, Maaike P, Bodmer, Danielle, Ausems, Margreet G E M, van Os, Theo A, Asperen, Christi J, Blok, Marinus J, Meijers-Heijboer, Hanne E J, Peock, Susan, Cook, Margaret, Oliver, Clare, Frost, Debra, Dunning, Alison M, Evans, D Gareth, Eeles, Ros, Pichert, Gabriella, Cole, Trevor, Hodgson, Shirley, Brewer, Carole, Morrison, Patrick J, Porteous, Mary, Kennedy, M John, Rogers, Mark T, Side, Lucy E, Donaldson, Alan, Gregory, Helen, Godwin, Andrew, Stoppa-Lyonnet, Dominique, Moncoutier, Virginie, Castera, Laurent, Mazoyer, Sylvie, Barjhoux, Laure, Bonadona, Valérie, Leroux, Dominique, Faivre, Laurence, Lidereau, Rosette, Nogues, Catherine, Bignon, Yves-Jean, Prieur, Fabienne, Collonge-Rame, Marie-Agnès, Venat-Bouvet, Laurence, Fert-Ferrer, Sandra, Miron, Alex, Buys, Saundra S, Hopper, John L, Daly, Mary B, John, Esther M, Terry, Mary Beth, Goldgar, David, Hansen, Thomas v O, Jønson, Lars, Ejlertsen, Bent, Agnarsson, Bjarni A, Offit, Kenneth, Kirchhoff, Tomas, Vijai, Joseph, Dutra-Clarke, Ana V C, Przybylo, Jennifer A, Montagna, Marco, Casella, Cinzia, Imyanitov, Evgeny N, Janavicius, Ramunas, Blanco, Ignacio, Lázaro, Conxi, Moysich, Kirsten B, Karlan, Beth Y, Gross, Jenny, Beattie, Mary S, Schmutzler, Rita, Wappenschmidt, Barbara, Meindl, Alfons, Ruehl, Ina, Fiebig, Britta, Sutter, Christian, Arnold, Norbert, Deissler, Helmut, Varon-Mateeva, Raymonda, Kast, Karin, Niederacher, Dieter, Gadzicki, Dorothea, Caldes, Trinidad, de la Hoya, Miguel, Nevanlinna, Heli, Aittomäki, Kristiina, Simard, Jacques, Soucy, Penny, Spurdle, Amanda B, Holland, Helene, Chenevix-Trench, Georgia, Easton, Douglas F, Antoniou, Antonis C

المساهمون: Department of Gynaecological Oncology, UCL EGA Institute for Women's Health, University College London, London, UK. sramus@usc.edu

مصطلحات موضوعية: Adult, Aged, 80 and over, Alleles, Chromosomes, Human, Pair 9, Female, Genes, BRCA1, BRCA2, Genotype, Germ-Line Mutation, Heterozygote, Humans, Likelihood Functions, Middle Aged, Odds Ratio, Ovarian Neoplasms, Polymorphism, Single Nucleotide, Retrospective Studies, Risk Factors

الوصف: To access publisher full text version of this article. Please click on the hyperlink in Additional Links field. ; BACKGROUND: Germline mutations in the BRCA1 and BRCA2 genes are associated with increased risks of breast and ovarian cancers. Although several common variants have been associated with breast cancer susceptibility in mutation carriers, none have been associated with ovarian cancer susceptibility. A genome-wide association study recently identified an association between the rare allele of the single-nucleotide polymorphism (SNP) rs3814113 (ie, the C allele) at 9p22.2 and decreased risk of ovarian cancer for women in the general population. We evaluated the association of this SNP with ovarian cancer risk among BRCA1 or BRCA2 mutation carriers by use of data from the Consortium of Investigators of Modifiers of BRCA1/2. METHODS: We genotyped rs3814113 in 10,029 BRCA1 mutation carriers and 5837 BRCA2 mutation carriers. Associations with ovarian and breast cancer were assessed with a retrospective likelihood approach. All statistical tests were two-sided. RESULTS: The minor allele of rs3814113 was associated with a reduced risk of ovarian cancer among BRCA1 mutation carriers (per-allele hazard ratio of ovarian cancer = 0.78, 95% confidence interval = 0.72 to 0.85; P = 4.8 × 10(-9)) and BRCA2 mutation carriers (hazard ratio of ovarian cancer = 0.78, 95% confidence interval = 0.67 to 0.90; P = 5.5 × 10(-4)). This SNP was not associated with breast cancer risk among either BRCA1 or BRCA2 mutation carriers. BRCA1 mutation carriers with the TT genotype at SNP rs3814113 were predicted to have an ovarian cancer risk to age 80 years of 48%, and those with the CC genotype were predicted to have a risk of 33%. CONCLUSION: Common genetic variation at the 9p22.2 locus was associated with decreased risk of ovarian cancer for carriers of a BRCA1 or BRCA2 mutation. ; National Cancer Institute (NCI) National Institutes of Health RFA-CA-06-503 P50 CA83638 U01 CA69631 5U01 CA113916 R01 CA128978 P50 CA116201 R01 CA74415 ...

العلاقة: http://dx.doi.org/10.1093/jnci/djq494Test; J. Natl. Cancer Inst. 2011, 103(2):105-16; http://hdl.handle.net/2336/227832Test; Journal of the National Cancer Institute

الإتاحة: https://doi.org/10.1093/jnci/djq494Test
http://hdl.handle.net/2336/227832Test

المؤلفون: Antoniou, Antonis C, Kartsonaki, Christiana, Sinilnikova, Olga M, Soucy, Penny, McGuffog, Lesley, Healey, Sue, Lee, Andrew, Peterlongo, Paolo, Manoukian, Siranoush, Peissel, Bernard, Zaffaroni, Daniela, Cattaneo, Elisa, Barile, Monica, Pensotti, Valeria, Pasini, Barbara, Dolcetti, Riccardo, Giannini, Giuseppe, Putignano, Anna Laura, Varesco, Liliana, Radice, Paolo, Mai, Phuong L, Greene, Mark H, Andrulis, Irene L, Glendon, Gord, Ozcelik, Hilmi, Thomassen, Mads, Gerdes, Anne-Marie, Kruse, Torben A, Birk Jensen, Uffe, Crüger, Dorthe G, Caligo, Maria A, Laitman, Yael, Milgrom, Roni, Kaufman, Bella, Paluch-Shimon, Shani, Friedman, Eitan, Loman, Niklas, Harbst, Katja, Lindblom, Annika, Arver, Brita, Ehrencrona, Hans, Melin, Beatrice, Nathanson, Katherine L, Domchek, Susan M, Rebbeck, Timothy, Jakubowska, Ania, Lubinski, Jan, Gronwald, Jacek, Huzarski, Tomasz, Byrski, Tomasz, Cybulski, Cezary, Gorski, Bohdan, Osorio, Ana, Ramón y Cajal, Teresa, Fostira, Florentia, Andrés, Raquel, Benitez, Javier, Hamann, Ute, Hogervorst, Frans B, Rookus, Matti A, Hooning, Maartje J, Nelen, Marcel R, van der Luijt, Rob B, van Os, Theo A M, van Asperen, Christi J, Devilee, Peter, Meijers-Heijboer, Hanne E J, Gómez Garcia, Encarna B, Peock, Susan, Cook, Margaret, Frost, Debra, Platte, Radka, Leyland, Jean, Evans, D Gareth, Lalloo, Fiona, Eeles, Ros, Izatt, Louise, Adlard, Julian, Davidson, Rosemarie, Eccles, Diana, Ong, Kai-ren, Cook, Jackie, Douglas, Fiona, Paterson, Joan, Kennedy, M John, Miedzybrodzka, Zosia, Godwin, Andrew, Stoppa-Lyonnet, Dominique, Buecher, Bruno, Belotti, Muriel, Tirapo, Carole, Mazoyer, Sylvie, Barjhoux, Laure, Lasset, Christine, Leroux, Dominique, Faivre, Laurence, Bronner, Myriam, Prieur, Fabienne, Nogues, Catherine, Rouleau, Etienne, Pujol, Pascal, Coupier, Isabelle, Frénay, Marc, Hopper, John L, Daly, Mary B, Terry, Mary B, John, Esther M, Buys, Saundra S, Yassin, Yosuf, Miron, Alexander, Goldgar, David, Singer, Christian F, Tea, Muy-Kheng, Pfeiler, Georg, Dressler, Anne Catharina, Hansen, Thomas v O, Jønson, Lars, Ejlertsen, Bent, Barkardottir, Rosa Bjork, Kirchhoff, Tomas, Offit, Kenneth, Piedmonte, Marion, Rodriguez, Gustavo, Small, Laurie, Boggess, John, Blank, Stephanie, Basil, Jack, Azodi, Masoud, Toland, Amanda Ewart, Montagna, Marco, Tognazzo, Silvia, Agata, Simona, Imyanitov, Evgeny, Janavicius, Ramunas, Lazaro, Conxi, Blanco, Ignacio, Pharoah, Paul D P, Sucheston, Lara, Karlan, Beth Y, Walsh, Christine S, Olah, Edith, Bozsik, Aniko, Teo, Soo-Hwang, Seldon, Joyce L, Beattie, Mary S, van Rensburg, Elizabeth J, Sluiter, Michelle D, Diez, Orland, Schmutzler, Rita K, Wappenschmidt, Barbara, Engel, Christoph, Meindl, Alfons, Ruehl, Ina, Varon-Mateeva, Raymonda, Kast, Karin, Deissler, Helmut, Niederacher, Dieter, Arnold, Norbert, Gadzicki, Dorothea, Schönbuchner, Ines, Caldes, Trinidad, de la Hoya, Miguel, Nevanlinna, Heli, Aittomäki, Kristiina, Dumont, Martine, Chiquette, Jocelyne, Tischkowitz, Marc, Chen, Xiaoqing, Beesley, Jonathan, Spurdle, Amanda B, Neuhausen, Susan L, Chun Ding, Yuan, Fredericksen, Zachary, Wang, Xianshu, Pankratz, Vernon S, Couch, Fergus, Simard, Jacques, Easton, Douglas F, Chenevix-Trench, Georgia

المساهمون: Department of Public Health and Primary Care, Centre for Cancer Genetic Epidemiology, University of Cambridge, Cambridge, UK. antonis@srl.cam.ac.uk

مصطلحات موضوعية: Adult, Aged, Alleles, BRCA1 Protein, BRCA2 Protein, Breast Neoplasms, Chromosomes, Human, Pair 1, Pair 6, Female, Genetic Predisposition to Disease, Heterozygote, Humans, Middle Aged, Mutation, Polymorphism, Single Nucleotide, Risk Factors

الوصف: To access publisher full text version of this article. Please click on the hyperlink in Additional Links field. ; Two single nucleotide polymorphisms (SNPs) at 6q25.1, near the ESR1 gene, have been implicated in the susceptibility to breast cancer for Asian (rs2046210) and European women (rs9397435). A genome-wide association study in Europeans identified two further breast cancer susceptibility variants: rs11249433 at 1p11.2 and rs999737 in RAD51L1 at 14q24.1. Although previously identified breast cancer susceptibility variants have been shown to be associated with breast cancer risk for BRCA1 and BRCA2 mutation carriers, the involvement of these SNPs to breast cancer susceptibility in mutation carriers is currently unknown. To address this, we genotyped these SNPs in BRCA1 and BRCA2 mutation carriers from 42 studies from the Consortium of Investigators of Modifiers of BRCA1/2. In the analysis of 14 123 BRCA1 and 8053 BRCA2 mutation carriers of European ancestry, the 6q25.1 SNPs (r(2) = 0.14) were independently associated with the risk of breast cancer for BRCA1 mutation carriers [hazard ratio (HR) = 1.17, 95% confidence interval (CI): 1.11-1.23, P-trend = 4.5 × 10(-9) for rs2046210; HR = 1.28, 95% CI: 1.18-1.40, P-trend = 1.3 × 10(-8) for rs9397435], but only rs9397435 was associated with the risk for BRCA2 carriers (HR = 1.14, 95% CI: 1.01-1.28, P-trend = 0.031). SNP rs11249433 (1p11.2) was associated with the risk of breast cancer for BRCA2 mutation carriers (HR = 1.09, 95% CI: 1.02-1.17, P-trend = 0.015), but was not associated with breast cancer risk for BRCA1 mutation carriers (HR = 0.97, 95% CI: 0.92-1.02, P-trend = 0.20). SNP rs999737 (RAD51L1) was not associated with breast cancer risk for either BRCA1 or BRCA2 mutation carriers (P-trend = 0.27 and 0.30, respectively). The identification of SNPs at 6q25.1 associated with breast cancer risk for BRCA1 mutation carriers will lead to a better understanding of the biology of tumour development in these women. ; The study was supported by the Icelandic ...

العلاقة: http://dx.doi.org/10.1093/hmg/ddr226Test; Hum. Mol. Genet. 2011, 20(16):3304-21; http://hdl.handle.net/2336/223211Test; Human molecular genetics

الإتاحة: https://doi.org/10.1093/hmg/ddr226Test
http://hdl.handle.net/2336/223211Test

المؤلفون: Antoniou, Antonis C, Beesley, Jonathan, McGuffog, Lesley, Sinilnikova, Olga M, Healey, Sue, Neuhausen, Susan L, Ding, Yuan Chun, Rebbeck, Timothy R, Weitzel, Jeffrey N, Lynch, Henry T, Isaacs, Claudine, Ganz, Patricia A, Tomlinson, Gail, Olopade, Olufunmilayo I, Couch, Fergus J, Wang, Xianshu, Lindor, Noralane M, Pankratz, Vernon S, Radice, Paolo, Manoukian, Siranoush, Peissel, Bernard, Zaffaroni, Daniela, Barile, Monica, Viel, Alessandra, Allavena, Anna, Dall'Olio, Valentina, Peterlongo, Paolo, Szabo, Csilla I, Zikan, Michal, Claes, Kathleen, Poppe, Bruce, Foretova, Lenka, Mai, Phuong L, Greene, Mark H, Rennert, Gad, Lejbkowicz, Flavio, Glendon, Gord, Ozcelik, Hilmi, Andrulis, Irene L, Thomassen, Mads, Gerdes, Anne-Marie, Sunde, Lone, Cruger, Dorthe, Birk Jensen, Uffe, Caligo, Maria, Friedman, Eitan, Kaufman, Bella, Laitman, Yael, Milgrom, Roni, Dubrovsky, Maya, Cohen, Shimrit, Borg, Ake, Jernström, Helena, Lindblom, Annika, Rantala, Johanna, Stenmark-Askmalm, Marie, Melin, Beatrice, Nathanson, Kate, Domchek, Susan, Jakubowska, Ania, Lubinski, Jan, Huzarski, Tomasz, Osorio, Ana, Lasa, Adriana, Durán, Mercedes, Tejada, Maria-Isabel, Godino, Javier, Benitez, Javier, Hamann, Ute, Kriege, Mieke, Hoogerbrugge, Nicoline, van der Luijt, Rob B, van Asperen, Christi J, Devilee, Peter, Meijers-Heijboer, E J, Blok, Marinus J, Aalfs, Cora M, Hogervorst, Frans, Rookus, Matti, Cook, Margaret, Oliver, Clare, Frost, Debra, Conroy, Don, Evans, D Gareth, Lalloo, Fiona, Pichert, Gabriella, Davidson, Rosemarie, Cole, Trevor, Cook, Jackie, Paterson, Joan, Hodgson, Shirley, Morrison, Patrick J, Porteous, Mary E, Walker, Lisa, Kennedy, M John, Dorkins, Huw, Peock, Susan, Godwin, Andrew K, Stoppa-Lyonnet, Dominique, de Pauw, Antoine, Mazoyer, Sylvie, Bonadona, Valérie, Lasset, Christine, Dreyfus, Hélène, Leroux, Dominique, Hardouin, Agnès, Berthet, Pascaline, Faivre, Laurence, Loustalot, Catherine, Noguchi, Tetsuro, Sobol, Hagay, Rouleau, Etienne, Nogues, Catherine, Frénay, Marc, Vénat-Bouvet, Laurence, Hopper, John L, Daly, Mary B, Terry, Mary B, John, Esther M, Buys, Saundra S, Yassin, Yosuf, Miron, Alexander, Goldgar, David, Singer, Christian F, Dressler, Anne Catharina, Gschwantler-Kaulich, Daphne, Pfeiler, Georg, Hansen, Thomas V O, Jønson, Lars, Agnarsson, Bjarni A, Kirchhoff, Tomas, Offit, Kenneth, Devlin, Vincent, Dutra-Clarke, Ana, Piedmonte, Marion, Rodriguez, Gustavo C, Wakeley, Katie, Boggess, John F, Basil, Jack, Schwartz, Peter E, Blank, Stephanie V, Toland, Amanda Ewart, Montagna, Marco, Casella, Cinzia, Imyanitov, Evgeny, Tihomirova, Laima, Blanco, Ignacio, Lazaro, Conxi, Ramus, Susan J, Sucheston, Lara, Karlan, Beth Y, Gross, Jenny, Schmutzler, Rita, Wappenschmidt, Barbara, Engel, Christoph, Meindl, Alfons, Lochmann, Magdalena, Arnold, Norbert, Heidemann, Simone, Varon-Mateeva, Raymonda, Niederacher, Dieter, Sutter, Christian, Deissler, Helmut, Gadzicki, Dorothea, Preisler-Adams, Sabine, Kast, Karin, Schönbuchner, Ines, Caldes, Trinidad, de la Hoya, Miguel, Aittomäki, Kristiina, Nevanlinna, Heli, Simard, Jacques, Spurdle, Amanda B, Holland, Helene, Chen, Xiaoqing, Platte, Radka, Chenevix-Trench, Georgia, Easton, Douglas F

المساهمون: Center for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK. antonis@srl.cam.ac.uk

مصطلحات موضوعية: Adult, Aged, 80 and over, Alleles, BRCA1 Protein, BRCA2 Protein, Breast Neoplasms, Female, Genetic Predisposition to Disease, Genotype, Heterozygote, Humans, Middle Aged, Mutation, Polymorphism, Single Nucleotide, Receptors, Progesterone, Risk Assessment, Risk Factors, Sodium-Bicarbonate Symporters, Survival Analysis, Vesicular Transport Proteins

الوصف: To access publisher full text version of this article. Please click on the hyperlink in Additional Links field ; The known breast cancer susceptibility polymorphisms in FGFR2, TNRC9/TOX3, MAP3K1, LSP1, and 2q35 confer increased risks of breast cancer for BRCA1 or BRCA2 mutation carriers. We evaluated the associations of 3 additional single nucleotide polymorphisms (SNPs), rs4973768 in SLC4A7/NEK10, rs6504950 in STXBP4/COX11, and rs10941679 at 5p12, and reanalyzed the previous associations using additional carriers in a sample of 12,525 BRCA1 and 7,409 BRCA2 carriers. Additionally, we investigated potential interactions between SNPs and assessed the implications for risk prediction. The minor alleles of rs4973768 and rs10941679 were associated with increased breast cancer risk for BRCA2 carriers (per-allele HR = 1.10, 95% CI: 1.03-1.18, P = 0.006 and HR = 1.09, 95% CI: 1.01-1.19, P = 0.03, respectively). Neither SNP was associated with breast cancer risk for BRCA1 carriers, and rs6504950 was not associated with breast cancer for either BRCA1 or BRCA2 carriers. Of the 9 polymorphisms investigated, 7 were associated with breast cancer for BRCA2 carriers (FGFR2, TOX3, MAP3K1, LSP1, 2q35, SLC4A7, 5p12, P = 7 × 10(-11) - 0.03), but only TOX3 and 2q35 were associated with the risk for BRCA1 carriers (P = 0.0049, 0.03, respectively). All risk-associated polymorphisms appear to interact multiplicatively on breast cancer risk for mutation carriers. Based on the joint genotype distribution of the 7 risk-associated SNPs in BRCA2 mutation carriers, the 5% of BRCA2 carriers at highest risk (i.e., between 95th and 100th percentiles) were predicted to have a probability between 80% and 96% of developing breast cancer by age 80, compared with 42% to 50% for the 5% of carriers at lowest risk. Our findings indicated that these risk differences might be sufficient to influence the clinical management of mutation carriers.

العلاقة: http://dx.doi.org/10.1158/0008-5472.CAN-10-1907Test; Cancer Res. 2010, 70(23):9742-54; http://hdl.handle.net/2336/129552Test; Cancer research

الإتاحة: https://doi.org/10.1158/0008-5472.CAN-10-1907Test
http://hdl.handle.net/2336/129552Test

المؤلفون: Hansen, Thomas van Overeem, Jønson, Lars, Albrechtsen, Anders, Steffensen, Ane Yde, Bergsten, Eva Boje, Myrhøj, Torben, Ejlertsen, Bent Laursen, Nielsen, Finn Cilius

المصدر: Hansen , T V O , Jønson , L , Albrechtsen , A , Steffensen , A Y , Bergsten , E B , Myrhøj , T , Ejlertsen , B L & Nielsen , F C 2010 , ' Identification of a novel BRCA1 nucleotide 4803delCC/c.4684delCC mutation and a nucleotide 249T >A/c.130T >A (p.Cys44Ser) mutation in two Greenlandic Inuit families : implications for genetic screening of Greenlandic Inuit families with high risk for breast and/or ovarian cancer ' , Breast Cancer Research and Treatment , vol. 124 , no. 1 , pp. 259-264 . https://doi.org/10.1007/s10549-010-0909-9Test

مصطلحات موضوعية: Adult, BRCA1 Protein, Base Sequence, Breast Neoplasms, Codon, Nonsense, DNA Mutational Analysis, Female, Founder Effect, Frameshift Mutation, Genetic Predisposition to Disease, Genetic Testing, Greenland, Heredity, Humans, Inuits, Middle Aged, Molecular Sequence Data, Ovarian Neoplasms, Pedigree, Risk Assessment, Risk Factors, Sequence Deletion

الوصف: Germ-line mutations in the tumour suppressor proteins BRCA1 and BRCA2 predispose to breast and ovarian cancer. We have recently identified a Greenlandic Inuit BRCA1 nucleotide 234T>G/c.115T>G (p.Cys39Gly) founder mutation, which at that time was the only disease-causing BRCA1/BRCA2 mutation identified in this population. Here, we describe the identification of a novel disease-causing BRCA1 nucleotide 4803delCC/c.4684delCC mutation in a Greenlandic Inuit with ovarian cancer. The mutation introduces a frameshift and a premature stop at codon 1572. We have also identified a BRCA1 nucleotide 249T>A/c.130T>A (p.Cys44Ser) mutation in another Greenlandic individual with ovarian cancer. This patient share a 1-2 Mb genomic fragment, containing the BRCA1 gene, with four Danish families harbouring the same mutation, suggesting that the 249T>A/c.130T>A (p.Cys44Ser) mutation originates from a Danish ancestor. We conclude that screening of Greenlandic Inuits with high risk of breast or ovarian cancer should include sequencing of the entire BRCA1 gene.

الإتاحة: https://doi.org/10.1007/s10549-010-0909-9Test
https://curis.ku.dk/portal/da/publications/identification-of-a-novel-brca1-nucleotide-4803delccc4684delcc-mutation-and-a-nucleotide-249tac130ta-pcys44ser-mutation-in-two-greenlandic-inuit-familiesTest(997f5ff0-41ed-4700-88f0-4c98a35c3f14).html