TY - JOUR A1 - Osorio, Ana A1 - Milne, Roger L. A1 - Kuchenbaecker, Karoline A1 - Vaclová, Tereza A1 - Pita, Guillermo A1 - Alonso, Rosario A1 - Peterlongo, Paolo A1 - Blanco, Ignacio A1 - de la Hoya, Miguel A1 - Duran, Mercedes A1 - Diez, Orland A1 - Ramón y Cajal, Teresa A1 - Konstantopoulou, Irene A1 - Martínez-Bouzas, Christina A1 - Conejero, Raquel Andrés A1 - Soucy, Penny A1 - McGuffog, Lesley A1 - Barrowdale, Daniel A1 - Lee, Andrew A1 - Arver, Brita A1 - Rantala, Johanna A1 - Loman, Niklas A1 - Ehrencrona, Hans A1 - Olopade, Olufunmilayo I. A1 - Beattie, Mary S. A1 - Domchek, Susan M. A1 - Nathanson, Katherine A1 - Rebbeck, Timothy R. A1 - Arun, Banu K. A1 - Karlan, Beth Y. A1 - Walsh, Christine A1 - Lester, Jenny A1 - John, Esther M. A1 - Whittemore, Alice S. A1 - Daly, Mary B. A1 - Southey, Melissa A1 - Hopper, John A1 - Terry, Mary B. A1 - Buys, Saundra S. A1 - Janavicius, Ramunas A1 - Dorfling, Cecilia M. A1 - van Rensburg, Elizabeth J. A1 - Steele, Linda A1 - Neuhausen, Susan L. A1 - Ding, Yuan Chun A1 - Hansen, Thomas V. O. A1 - Jønson, Lars A1 - Ejlertsen, Bent A1 - Gerdes, Anne-Marie A1 - Infante, Mar A1 - Herráez, Belén A1 - Moreno, Leticia Thais A1 - Weitzel, Jeffrey N. A1 - Herzog, Josef A1 - Weeman, Kisa A1 - Manoukian, Siranoush A1 - Peissel, Bernard A1 - Zaffaroni, Daniela A1 - Scuvera, Guilietta A1 - Bonanni, Bernardo A1 - Mariette, Frederique A1 - Volorio, Sara A1 - Viel, Alessandra A1 - Varesco, Liliana A1 - Papi, Laura A1 - Ottini, Laura A1 - Tibiletti, Maria Grazia A1 - Radice, Paolo A1 - Yannoukakos, Drakoulis A1 - Garber, Judy A1 - Ellis, Steve A1 - Frost, Debra A1 - Platte, Radka A1 - Fineberg, Elena A1 - Evans, Gareth A1 - Lalloo, Fiona A1 - Izatt, Louise A1 - Eeles, Ros A1 - Adlard, Julian A1 - Davidson, Rosemarie A1 - Cole, Trevor A1 - Eccles, Diana A1 - Cook, Jackie A1 - Hodgson, Shirley A1 - Brewer, Carole A1 - Tischkowitz, Marc A1 - Douglas, Fiona A1 - Porteous, Mary A1 - Side, Lucy A1 - Walker, Lisa A1 - Morrison, Patrick A1 - Donaldson, Alan A1 - Kennedy, John A1 - Foo, Claire A1 - Godwin, Andrew K. A1 - Schmutzler, Rita Katharina A1 - Wappenschmidt, Barbara A1 - Rhiem, Kerstin A1 - Engel, Christoph A1 - Meindl, Alftons A1 - Ditsch, Nina A1 - Arnold, Norbert A1 - Plendl, Hans Jörg A1 - Niederacher, Dieter A1 - Sutter, Christian A1 - Wang-Gohrke, Shan A1 - Steinemann, Doris A1 - Preisler-Adams, Sabine A1 - Kast, Karin A1 - Varon-Mateeva, Raymonda A1 - Gehrig, Andrea A1 - Stoppa-Lyonnet, Dominique A1 - Sinilnikova, Olga M. A1 - Mazoyer, Sylvie A1 - Damiola, Francesca A1 - Poppe, Bruce A1 - Claes, Kathleen A1 - Piedmonte, Marion A1 - Tucker, Kathy A1 - Backes, Floor A1 - Rodríguez, Gustavo A1 - Brewster, Wendy A1 - Wakeley, Katie A1 - Rutherford, Thomas A1 - Caldés, Trinidad A1 - Nevanlinna, Heli A1 - Aittomäki, Kristiina A1 - Rookus, Matti A. A1 - van Os, Theo A. M. A1 - van der Kolk, Lizet A1 - de Lange, J. L. A1 - Meijers-Heijboer, Hanne E. J. A1 - van der Hout, A. H. A1 - van Asperen, Christi J. A1 - Goméz Garcia, Encarna B. A1 - Encarna, B. A1 - Hoogerbrugge, Nicoline A1 - Collée, J. Margriet A1 - van Deurzen, Carolien H. M. A1 - van der Luijt, Rob B. A1 - Devilee, Peter A1 - Olah, Edith A1 - Lázaro, Conxi A1 - Teulé, Alex A1 - Menéndez, Mireia A1 - Jakubowska, Anna A1 - Cybulski, Cezary A1 - Gronwald, Jecek A1 - Lubinski, Jan A1 - Durda, Katarzyna A1 - Jaworska-Bieniek, Katarzyna A1 - Johannsson, Oskar Th. A1 - Maugard, Christine A1 - Montagna, Marco A1 - Tognazzo, Silvia A1 - Teixeira, Manuel R. A1 - Healey, Sue A1 - Olswold, Curtis A1 - Guidugli, Lucia A1 - Lindor, Noralane A1 - Slager, Susan A1 - Szabo, Csilla I. A1 - Vijai, Joseph A1 - Robson, Mark A1 - Kauff, Noah A1 - Zhang, Liying A1 - Rau-Murthy, Rohini A1 - Fink-Retter, Anneliese A1 - Singer, Christine F. A1 - Rappaport, Christine A1 - Kaulich, Daphne Geschwantler A1 - Pfeiler, Georg A1 - Tea, Muy-Kheng A1 - Berger, Andreas A1 - Phelan, Catherine M. A1 - Greene, Mark H. A1 - Mai, Phuong L. A1 - Lejbkowicz, Flavio A1 - Andrulis, Irene A1 - Mulligan, Anna Marie A1 - Glendon, Gord A1 - Toland, Amanda Ewart A1 - Bojesen, Anders A1 - Pedersen, Inge Sokilde A1 - Sunde, Lone A1 - Thomassen, Mads A1 - Kruse, Torben A. A1 - Jensen, Uffe Birk A1 - Friedman, Eitan A1 - Laitman, Yeal A1 - Shimon, Shanie Paluch A1 - Simard, Jaques A1 - Easton, Douglas F. A1 - Offit, Kenneth A1 - Couch, Fergus J. A1 - Chenevix-Trench, Georgia A1 - Antoniou, Antonis C. A1 - Benitez, Javier T1 - DNA Glycosylases Involved in Base Excision Repair May Be Associated with Cancer Risk in BRCA1 and BRCA2 Mutation Carriers JF - PLOS Genetics N2 - 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 = 2.7x10(-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 = 4.8x10(-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. KW - single-nucleotide polymorphisms KW - breast cancer KW - ovarian cancer KW - genetic modifiers KW - common variants KW - NEIL2 KW - OGG1 KW - investigators KW - consortium KW - damage Y1 - 2014 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-116820 SN - 1553-7404 VL - 4 IS - e1004256 ER - TY - JOUR A1 - Blein, Sophie A1 - Bardel, Claire A1 - Danjean, Vincent A1 - McGuffog, Lesley A1 - Healay, Sue A1 - Barrowdale, Daniel A1 - Lee, Andrew A1 - Dennis, Joe A1 - Kuchenbaecker, Karoline B. A1 - Soucy, Penny A1 - Terry, Mary Beth A1 - Chung, Wendy K. A1 - Goldgar, David E. A1 - Buys, Saundra S. A1 - Janavicius, Ramunas A1 - Tihomirova, Laima A1 - Tung, Nadine A1 - Dorfling, Cecilia M. A1 - van Rensburg, Elizabeth J. A1 - Neuhausen, Susan L. A1 - Ding, Yuan Chun A1 - Gerdes, Anne-Marie A1 - Ejlertsen, Bent A1 - Nielsen, Finn C. A1 - Hansen, Thomas V. O. A1 - Osorio, Ana A1 - Benitez, Javier A1 - Andreas Conejero, Raquel A1 - Segota, Ena A1 - Weitzel, Jeffrey N. A1 - Thelander, Margo A1 - Peterlongo, Paolo A1 - Radice, Paolo A1 - Pensotti, Valeria A1 - Dolcetti, Riccardo A1 - Bonanni, Bernardo A1 - Peissel, Bernard A1 - Zaffaroni, Daniela A1 - Scuvera, Giulietta A1 - Manoukian, Siranoush A1 - Varesco, Liliana A1 - Capone, Gabriele L. A1 - Papi, Laura A1 - Ottini, Laura A1 - Yannoukakos, Drakoulis A1 - Konstantopoulou, Irene A1 - Garber, Judy A1 - Hamann, Ute A1 - Donaldson, Alan A1 - Brady, Angela A1 - Brewer, Carole A1 - Foo, Claire A1 - Evans, D. Gareth A1 - Frost, Debra A1 - Eccles, Diana A1 - Douglas, Fiona A1 - Cook, Jackie A1 - Adlard, Julian A1 - Barwell, Julian A1 - Walker, Lisa A1 - Izatt, Louise A1 - Side, Lucy E. A1 - Kennedy, M. John A1 - Tischkowitz, Marc A1 - Rogers, Mark T. A1 - Porteous, Mary E. A1 - Morrison, Patrick J. A1 - Platte, Radka A1 - Eeles, Ros A1 - Davidson, Rosemarie A1 - Hodgson, Shirley A1 - Cole, Trevor A1 - Godwin, Andrew K A1 - Isaacs, Claudine A1 - Claes, Kathleen A1 - De Leeneer, Kim A1 - Meindl, Alfons A1 - Gehrig, Andrea A1 - Wappenschmidt, Barbara A1 - Sutter, Christian A1 - Engel, Christoph A1 - Niederacher, Dieter A1 - Steinemann, Doris A1 - Plendl, Hansjoerg A1 - Kast, Karin A1 - Rhiem, Kerstin A1 - Ditsch, Nina A1 - Arnold, Norbert A1 - Varon-Mateeva, Raymonda A1 - Schmutzler, Rita K. A1 - Preisler-Adams, Sabine A1 - Markov, Nadja Bogdanova A1 - Wang-Gohrke, Shan A1 - de Pauw, Antoine A1 - Lefol, Cedrick A1 - Lasset, Christine A1 - Leroux, Dominique A1 - Rouleau, Etienne A1 - Damiola, Francesca A1 - Dreyfus, Helene A1 - Barjhoux, Laure A1 - Golmard, Lisa A1 - Uhrhammer, Nancy A1 - Bonadona, Valerie A1 - Sornin, Valerie A1 - Bignon, Yves-Jean A1 - Carter, Jonathan A1 - Van Le, Linda A1 - Piedmonte, Marion A1 - DiSilvestro, Paul A. A1 - de la Hoya, Miguel A1 - Caldes, Trinidad A1 - Nevanlinna, Heli A1 - Aittomäki, Kristiina A1 - Jager, Agnes A1 - van den Ouweland, Ans M. W. A1 - Kets, Carolien M. A1 - Aalfs, Cora M. A1 - van Leeuwen, Flora E. A1 - Hogervorst, Frans B. L. A1 - Meijers-Heijboer, Hanne E. J. A1 - Oosterwijk, Jan C. A1 - van Roozendaal, Kees E. P. A1 - Rookus, Matti A. A1 - Devilee, Peter A1 - van der Luijt, Rob B. A1 - Olah, Edith A1 - Diez, Orland A1 - Teule, Alex A1 - Lazaro, Conxi A1 - Blanco, Ignacio A1 - Del Valle, Jesus A1 - Jakubowska, Anna A1 - Sukiennicki, Grzegorz A1 - Gronwald, Jacek A1 - Spurdle, Amanda B. A1 - Foulkes, William A1 - Olswold, Curtis A1 - Lindor, Noralene M. A1 - Pankratz, Vernon S. A1 - Szabo, Csilla I. A1 - Lincoln, Anne A1 - Jacobs, Lauren A1 - Corines, Marina A1 - Robson, Mark A1 - Vijai, Joseph A1 - Berger, Andreas A1 - Fink-Retter, Anneliese A1 - Singer, Christian F. A1 - Rappaport, Christine A1 - Geschwantler Kaulich, Daphne A1 - Pfeiler, Georg A1 - Tea, Muy-Kheng A1 - Greene, Mark H. A1 - Mai, Phuong L. A1 - Rennert, Gad A1 - Imyanitov, Evgeny N. A1 - Mulligan, Anna Marie A1 - Glendon, Gord A1 - Andrulis, Irene L. A1 - Tchatchou, Andrine A1 - Toland, Amanda Ewart A1 - Pedersen, Inge Sokilde A1 - Thomassen, Mads A1 - Kruse, Torben A. A1 - Jensen, Uffe Birk A1 - Caligo, Maria A. A1 - Friedman, Eitan A1 - Zidan, Jamal A1 - Laitman, Yael A1 - Lindblom, Annika A1 - Melin, Beatrice A1 - Arver, Brita A1 - Loman, Niklas A1 - Rosenquist, Richard A1 - Olopade, Olufunmilayo I. A1 - Nussbaum, Robert L. A1 - Ramus, Susan J. A1 - Nathanson, Katherine L. A1 - Domchek, Susan M. A1 - Rebbeck, Timothy R. A1 - Arun, Banu K. A1 - Mitchell, Gillian A1 - Karlan, Bethy Y. A1 - Lester, Jenny A1 - Orsulic, Sandra A1 - Stoppa-Lyonnet, Dominique A1 - Thomas, Gilles A1 - Simard, Jacques A1 - Couch, Fergus J. A1 - Offit, Kenenth A1 - Easton, Douglas F. A1 - Chenevix-Trench, Georgia A1 - Antoniou, Antonis C. A1 - Mazoyer, Sylvie A1 - Phelan, Catherine M. A1 - Sinilnikova, Olga M. A1 - Cox, David G. T1 - An original phylogenetic approach identified mitochondrial haplogroup T1a1 as inversely associated with breast cancer risk in BRCA2 mutation carriers JF - Breast Cancer Research N2 - Introduction: Individuals carrying pathogenic mutations in the BRCA1 and BRCA2 genes have a high lifetime risk of breast cancer. BRCA1 and BRCA2 are involved in DNA double-strand break repair, DNA alterations that can be caused by exposure to reactive oxygen species, a main source of which are mitochondria. Mitochondrial genome variations affect electron transport chain efficiency and reactive oxygen species production. Individuals with different mitochondrial haplogroups differ in their metabolism and sensitivity to oxidative stress. Variability in mitochondrial genetic background can alter reactive oxygen species production, leading to cancer risk. In the present study, we tested the hypothesis that mitochondrial haplogroups modify breast cancer risk in BRCA1/2 mutation carriers. Methods: We genotyped 22,214 (11,421 affected, 10,793 unaffected) mutation carriers belonging to the Consortium of Investigators of Modifiers of BRCA1/2 for 129 mitochondrial polymorphisms using the iCOGS array. Haplogroup inference and association detection were performed using a phylogenetic approach. ALTree was applied to explore the reference mitochondrial evolutionary tree and detect subclades enriched in affected or unaffected individuals. Results: We discovered that subclade T1a1 was depleted in affected BRCA2 mutation carriers compared with the rest of clade T (hazard ratio (HR) = 0.55; 95% confidence interval (CI), 0.34 to 0.88; P = 0.01). Compared with the most frequent haplogroup in the general population (that is, H and T clades), the T1a1 haplogroup has a HR of 0.62 (95% CI, 0.40 to 0.95; P = 0.03). We also identified three potential susceptibility loci, including G13708A/rs28359178, which has demonstrated an inverse association with familial breast cancer risk. Conclusions: This study illustrates how original approaches such as the phylogeny-based method we used can empower classical molecular epidemiological studies aimed at identifying association or risk modification effects. KW - single-nucleotide polymorphisms KW - genetic modifiers KW - oxidative stress KW - consortium KW - multiple diseases KW - DNA KW - haplogroups KW - susceptibility KW - Ovarian KW - variants Y1 - 2015 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-145458 VL - 17 IS - 61 ER -