Directly to content
  1. Publishing |
  2. Search |
  3. Browse |
  4. Recent items rss |
  5. Open Access |
  6. Jur. Issues |
  7. DeutschClear Cookie - decide language by browser settings

An original phylogenetic approach identified mitochondrial haplogroup T1a1 as inversely associated with breast cancer risk in BRCA2 mutation carriers

Blein, Sophie ; Bardel, Claire ; Danjean, Vincent ; McGuffog, Lesley ; Healey, Sue ; Barrowdale, Daniel ; Lee, Andrew ; Dennis, Joe ; Kuchenbaecker, Karoline B. ; Soucy, Penny ; Terry, Mary B. ; Chung, Wendy K. ; Goldgar, David E. ; Buys, Saundra S. ; Janavicius, Ramunas ; Tihomirova, Laima ; Tung, Nadine ; Dorfling, Cecilia M. ; van Rensburg, Elizabeth J. ; Neuhausen, Susan L. ; Ding, Yuan Chun ; Gerdes, Anne-Marie ; Ejlertsen, Bent ; Nielsen, Finn C. ; Hansen, Thomas VO ; Osorio, Ana ; Benitez, Javier ; Conejero, Raquel Andrés ; Segota, Ena ; Weitzel, Jeffrey N. ; Thelander, Margo ; Peterlongo, Paolo ; Radice, Paolo ; Pensotti, Valeria ; Dolcetti, Riccardo ; Bonanni, Bernardo ; Peissel, Bernard ; Zaffaroni, Daniela ; Scuvera, Giulietta ; Manoukian, Siranoush ; Varesco, Liliana ; Capone, Gabriele L. ; Papi, Laura ; Ottini, Laura ; Yannoukakos, Drakoulis ; Konstantopoulou, Irene ; Garber, Judy ; Hamann, Ute ; Donaldson, Alan ; Brady, Angela ; Brewer, Carole ; Foo, Claire ; Evans, D. Gareth ; Frost, Debra ; Eccles, Diana ; Douglas, Fiona ; Cook, Jackie ; Adlard, Julian ; Barwell, Julian ; Walker, Lisa ; Izatt, Louise ; Side, Lucy E. ; Kennedy, M John ; Tischkowitz, Marc ; Rogers, Mark T ; Porteous, Mary E ; Morrison, Patrick J ; Platte, Radka ; Eeles, Ros ; Davidson, Rosemarie ; Hodgson, Shirley ; Cole, Trevor ; Godwin, Andrew K ; Isaacs, Claudine ; Claes, Kathleen ; De Leeneer, Kim ; Meindl, Alfons ; Gehrig, Andrea ; Wappenschmidt, Barbara ; Sutter, Christian ; Engel, Christoph ; Niederacher, Dieter ; Steinemann, Doris ; Plendl, Hansjörg ; Kast, Karin ; Rhiem, Kerstin ; Ditsch, Nina ; Arnold, Norbert ; Varon-Mateeva, Raymonda ; Schmutzler, Rita K. ; Preisler-Adams, Sabine ; Markov, Nadja B. ; Wang-Gohrke, Shan ; de Pauw, Antoine ; Lefol, Cédrick ; Lasset, Christine ; Leroux, Dominique ; Rouleau, Etienne ; Damiola, Francesca ; Dreyfus, Hélène ; Barjhoux, Laure ; Golmard, Lisa ; Uhrhammer, Nancy ; Bonadona, Valérie ; Sornin, Valérie ; Bignon, Yves-Jean ; Carter, Jonathan ; Van Le, Linda ; Piedmonte, Marion ; DiSilvestro, Paul A. ; de la Hoya, Miguel ; Caldes, Trinidad ; Nevanlinna, Heli ; Aittomäki, Kristiina ; Jager, Agnes ; van den Ouweland, Ans MW ; Kets, Carolien M. ; Aalfs, Cora M. ; van Leeuwen, Flora E. ; Hogervorst, Frans BL ; Meijers-Heijboer, Hanne EJ ; Oosterwijk, Jan C. ; van Roozendaal, Kees EP ; Rookus, Matti A. ; Devilee, Peter ; van der Luijt, Rob B. ; Olah, Edith ; Diez, Orland ; Teulé, Alex ; Lazaro, Conxi ; Blanco, Ignacio ; Del Valle, Jesús ; Jakubowska, Anna ; Sukiennicki, Grzegorz ; Gronwald, Jacek ; Lubinski, Jan ; Durda, Katarzyna ; Jaworska-Bieniek, Katarzyna ; Agnarsson, Bjarni A. ; Maugard, Christine ; Amadori, Alberto ; Montagna, Marco ; Teixeira, Manuel R. ; Spurdle, Amanda B. ; Foulkes, William ; Olswold, Curtis ; Lindor, Noralane M. ; Pankratz, Vernon S. ; Szabo, Csilla I. ; Lincoln, Anne ; Jacobs, Lauren ; Corines, Marina ; Robson, Mark ; Vijai, Joseph ; Berger, Andreas ; Fink-Retter, Anneliese ; Singer, Christian F. ; Rappaport, Christine ; Geschwantler Kaulich, Daphne ; Pfeiler, Georg ; Tea, Muy-Kheng ; Greene, Mark H. ; Mai, Phuong L. ; Rennert, Gad ; Imyanitov, Evgeny N. ; Mulligan, Anna Marie ; Glendon, Gord ; Andrulis, Irene L ; Tchatchou, Sandrine ; Ewart Toland, Amanda ; Sokilde Pedersen, Inge ; Thomassen, Mads ; Kruse, Torben A. ; Jensen, Uffe Birk ; Caligo, Maria A. ; Friedman, Eitan ; Zidan, Jamal ; Laitman, Yael ; Lindblom, Annika ; Melin, Beatrice ; Arver, Brita ; Loman, Niklas ; Rosenquist, Richard ; Olopade, Olufunmilayo I. ; Nussbaum, Robert L. ; Ramus, Susan J. ; Nathanson, Katherine L. ; Domchek, Susan M. ; Rebbeck, Timothy R. ; Arun, Banu K. ; Mitchell, Gillian ; Karlan, Beth Y. ; Lester, Jenny ; Orsulic, Sandra ; Stoppa-Lyonnet, Dominique ; Thomas, Gilles ; Simard, Jacques ; Couch, Fergus J. ; Offit, Kenneth ; Easton, Douglas F. ; Chenevix-Trench, Georgia ; Antoniou, Antonis C. ; Mazoyer, Sylvie ; Phelan, Catherine M. ; Sinilnikova, Olga M. ; Cox, David G.

In: Breast Cancer Research, 17 (2015), Nr. 61. pp. 1-15. ISSN 1465-542X

[thumbnail of 13058_2015_Article_567.pdf]
Preview
PDF, English
Download (1MB) | Lizenz: Creative Commons LizenzvertragAn original phylogenetic approach identified mitochondrial haplogroup T1a1 as inversely associated with breast cancer risk in BRCA2 mutation carriers by Blein, Sophie ; Bardel, Claire ; Danjean, Vincent ; McGuffog, Lesley ; Healey, Sue ; Barrowdale, Daniel ; Lee, Andrew ; Dennis, Joe ; Kuchenbaecker, Karoline B. ; Soucy, Penny ; Terry, Mary B. ; Chung, Wendy K. ; Goldgar, David E. ; Buys, Saundra S. ; Janavicius, Ramunas ; Tihomirova, Laima ; Tung, Nadine ; Dorfling, Cecilia M. ; van Rensburg, Elizabeth J. ; Neuhausen, Susan L. ; Ding, Yuan Chun ; Gerdes, Anne-Marie ; Ejlertsen, Bent ; Nielsen, Finn C. ; Hansen, Thomas VO ; Osorio, Ana ; Benitez, Javier ; Conejero, Raquel Andrés ; Segota, Ena ; Weitzel, Jeffrey N. ; Thelander, Margo ; Peterlongo, Paolo ; Radice, Paolo ; Pensotti, Valeria ; Dolcetti, Riccardo ; Bonanni, Bernardo ; Peissel, Bernard ; Zaffaroni, Daniela ; Scuvera, Giulietta ; Manoukian, Siranoush ; Varesco, Liliana ; Capone, Gabriele L. ; Papi, Laura ; Ottini, Laura ; Yannoukakos, Drakoulis ; Konstantopoulou, Irene ; Garber, Judy ; Hamann, Ute ; Donaldson, Alan ; Brady, Angela ; Brewer, Carole ; Foo, Claire ; Evans, D. Gareth ; Frost, Debra ; Eccles, Diana ; Douglas, Fiona ; Cook, Jackie ; Adlard, Julian ; Barwell, Julian ; Walker, Lisa ; Izatt, Louise ; Side, Lucy E. ; Kennedy, M John ; Tischkowitz, Marc ; Rogers, Mark T ; Porteous, Mary E ; Morrison, Patrick J ; Platte, Radka ; Eeles, Ros ; Davidson, Rosemarie ; Hodgson, Shirley ; Cole, Trevor ; Godwin, Andrew K ; Isaacs, Claudine ; Claes, Kathleen ; De Leeneer, Kim ; Meindl, Alfons ; Gehrig, Andrea ; Wappenschmidt, Barbara ; Sutter, Christian ; Engel, Christoph ; Niederacher, Dieter ; Steinemann, Doris ; Plendl, Hansjörg ; Kast, Karin ; Rhiem, Kerstin ; Ditsch, Nina ; Arnold, Norbert ; Varon-Mateeva, Raymonda ; Schmutzler, Rita K. ; Preisler-Adams, Sabine ; Markov, Nadja B. ; Wang-Gohrke, Shan ; de Pauw, Antoine ; Lefol, Cédrick ; Lasset, Christine ; Leroux, Dominique ; Rouleau, Etienne ; Damiola, Francesca ; Dreyfus, Hélène ; Barjhoux, Laure ; Golmard, Lisa ; Uhrhammer, Nancy ; Bonadona, Valérie ; Sornin, Valérie ; Bignon, Yves-Jean ; Carter, Jonathan ; Van Le, Linda ; Piedmonte, Marion ; DiSilvestro, Paul A. ; de la Hoya, Miguel ; Caldes, Trinidad ; Nevanlinna, Heli ; Aittomäki, Kristiina ; Jager, Agnes ; van den Ouweland, Ans MW ; Kets, Carolien M. ; Aalfs, Cora M. ; van Leeuwen, Flora E. ; Hogervorst, Frans BL ; Meijers-Heijboer, Hanne EJ ; Oosterwijk, Jan C. ; van Roozendaal, Kees EP ; Rookus, Matti A. ; Devilee, Peter ; van der Luijt, Rob B. ; Olah, Edith ; Diez, Orland ; Teulé, Alex ; Lazaro, Conxi ; Blanco, Ignacio ; Del Valle, Jesús ; Jakubowska, Anna ; Sukiennicki, Grzegorz ; Gronwald, Jacek ; Lubinski, Jan ; Durda, Katarzyna ; Jaworska-Bieniek, Katarzyna ; Agnarsson, Bjarni A. ; Maugard, Christine ; Amadori, Alberto ; Montagna, Marco ; Teixeira, Manuel R. ; Spurdle, Amanda B. ; Foulkes, William ; Olswold, Curtis ; Lindor, Noralane M. ; Pankratz, Vernon S. ; Szabo, Csilla I. ; Lincoln, Anne ; Jacobs, Lauren ; Corines, Marina ; Robson, Mark ; Vijai, Joseph ; Berger, Andreas ; Fink-Retter, Anneliese ; Singer, Christian F. ; Rappaport, Christine ; Geschwantler Kaulich, Daphne ; Pfeiler, Georg ; Tea, Muy-Kheng ; Greene, Mark H. ; Mai, Phuong L. ; Rennert, Gad ; Imyanitov, Evgeny N. ; Mulligan, Anna Marie ; Glendon, Gord ; Andrulis, Irene L ; Tchatchou, Sandrine ; Ewart Toland, Amanda ; Sokilde Pedersen, Inge ; Thomassen, Mads ; Kruse, Torben A. ; Jensen, Uffe Birk ; Caligo, Maria A. ; Friedman, Eitan ; Zidan, Jamal ; Laitman, Yael ; Lindblom, Annika ; Melin, Beatrice ; Arver, Brita ; Loman, Niklas ; Rosenquist, Richard ; Olopade, Olufunmilayo I. ; Nussbaum, Robert L. ; Ramus, Susan J. ; Nathanson, Katherine L. ; Domchek, Susan M. ; Rebbeck, Timothy R. ; Arun, Banu K. ; Mitchell, Gillian ; Karlan, Beth Y. ; Lester, Jenny ; Orsulic, Sandra ; Stoppa-Lyonnet, Dominique ; Thomas, Gilles ; Simard, Jacques ; Couch, Fergus J. ; Offit, Kenneth ; Easton, Douglas F. ; Chenevix-Trench, Georgia ; Antoniou, Antonis C. ; Mazoyer, Sylvie ; Phelan, Catherine M. ; Sinilnikova, Olga M. ; Cox, David G. underlies the terms of Creative Commons Attribution 3.0 Germany

Citation of documents: Please do not cite the URL that is displayed in your browser location input, instead use the DOI, URN or the persistent URL below, as we can guarantee their long-time accessibility.

Abstract

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.

Document type: Article
Journal or Publication Title: Breast Cancer Research
Volume: 17
Number: 61
Publisher: BioMed Central
Place of Publication: London
Date Deposited: 18 Jan 2016 13:05
Date: 2015
ISSN: 1465-542X
Page Range: pp. 1-15
Faculties / Institutes: Service facilities > German Cancer Research Center (DKFZ)
Medizinische Fakultät Heidelberg > Institut für Humangenetik
DDC-classification: 610 Medical sciences Medicine
About | FAQ | Contact | Imprint |
OA-LogoDINI certificate 2013Logo der Open-Archives-Initiative