title: An original phylogenetic approach identified mitochondrial haplogroup T1a1 as inversely associated with breast cancer risk in BRCA2 mutation carriers
creator: Blein, Sophie
creator: Bardel, Claire
creator: Danjean, Vincent
creator: McGuffog, Lesley
creator: Healey, Sue
creator: Barrowdale, Daniel
creator: Lee, Andrew
creator: Dennis, Joe
creator: Kuchenbaecker, Karoline B.
creator: Soucy, Penny
creator: Terry, Mary B.
creator: Chung, Wendy K.
creator: Goldgar, David E.
creator: Buys, Saundra S.
creator: Janavicius, Ramunas
creator: Tihomirova, Laima
creator: Tung, Nadine
creator: Dorfling, Cecilia M.
creator: van Rensburg, Elizabeth J.
creator: Neuhausen, Susan L.
creator: Ding, Yuan Chun
creator: Gerdes, Anne-Marie
creator: Ejlertsen, Bent
creator: Nielsen, Finn C.
creator: Hansen, Thomas VO
creator: Osorio, Ana
creator: Benitez, Javier
creator: Conejero, Raquel Andrés
creator: Segota, Ena
creator: Weitzel, Jeffrey N.
creator: Thelander, Margo
creator: Peterlongo, Paolo
creator: Radice, Paolo
creator: Pensotti, Valeria
creator: Dolcetti, Riccardo
creator: Bonanni, Bernardo
creator: Peissel, Bernard
creator: Zaffaroni, Daniela
creator: Scuvera, Giulietta
creator: Manoukian, Siranoush
creator: Varesco, Liliana
creator: Capone, Gabriele L.
creator: Papi, Laura
creator: Ottini, Laura
creator: Yannoukakos, Drakoulis
creator: Konstantopoulou, Irene
creator: Garber, Judy
creator: Hamann, Ute
creator: Donaldson, Alan
creator: Brady, Angela
creator: Brewer, Carole
creator: Foo, Claire
creator: Evans, D. Gareth
creator: Frost, Debra
creator: Eccles, Diana
creator: Douglas, Fiona
creator: Cook, Jackie
creator: Adlard, Julian
creator: Barwell, Julian
creator: Walker, Lisa
creator: Izatt, Louise
creator: Side, Lucy E.
creator: Kennedy, M John
creator: Tischkowitz, Marc
creator: Rogers, Mark T
creator: Porteous, Mary E
creator: Morrison, Patrick J
creator: Platte, Radka
creator: Eeles, Ros
creator: Davidson, Rosemarie
creator: Hodgson, Shirley
creator: Cole, Trevor
creator: Godwin, Andrew K
creator: Isaacs, Claudine
creator: Claes, Kathleen
creator: De Leeneer, Kim
creator: Meindl, Alfons
creator: Gehrig, Andrea
creator: Wappenschmidt, Barbara
creator: Sutter, Christian
creator: Engel, Christoph
creator: Niederacher, Dieter
creator: Steinemann, Doris
creator: Plendl, Hansjörg
creator: Kast, Karin
creator: Rhiem, Kerstin
creator: Ditsch, Nina
creator: Arnold, Norbert
creator: Varon-Mateeva, Raymonda
creator: Schmutzler, Rita K.
creator: Preisler-Adams, Sabine
creator: Markov, Nadja B.
creator: Wang-Gohrke, Shan
creator: de Pauw, Antoine
creator: Lefol, Cédrick
creator: Lasset, Christine
creator: Leroux, Dominique
creator: Rouleau, Etienne
creator: Damiola, Francesca
creator: Dreyfus, Hélène
creator: Barjhoux, Laure
creator: Golmard, Lisa
creator: Uhrhammer, Nancy
creator: Bonadona, Valérie
creator: Sornin, Valérie
creator: Bignon, Yves-Jean
creator: Carter, Jonathan
creator: Van Le, Linda
creator: Piedmonte, Marion
creator: DiSilvestro, Paul A.
creator: de la Hoya, Miguel
creator: Caldes, Trinidad
creator: Nevanlinna, Heli
creator: Aittomäki, Kristiina
creator: Jager, Agnes
creator: van den Ouweland, Ans MW
creator: Kets, Carolien M.
creator: Aalfs, Cora M.
creator: van Leeuwen, Flora E.
creator: Hogervorst, Frans BL
creator:  Meijers-Heijboer, Hanne EJ
creator: Oosterwijk, Jan C.
creator: van Roozendaal, Kees EP
creator: Rookus, Matti A.
creator: Devilee, Peter
creator: van der Luijt, Rob B.
creator: Olah, Edith
creator: Diez, Orland
creator: Teulé, Alex
creator: Lazaro, Conxi
creator: Blanco, Ignacio
creator: Del Valle, Jesús
creator: Jakubowska, Anna
creator: Sukiennicki, Grzegorz
creator: Gronwald, Jacek
creator: Lubinski, Jan
creator: Durda, Katarzyna
creator: Jaworska-Bieniek, Katarzyna
creator: Agnarsson, Bjarni A.
creator: Maugard, Christine
creator: Amadori, Alberto
creator: Montagna, Marco
creator: Teixeira, Manuel R.
creator: Spurdle, Amanda B.
creator: Foulkes, William
creator: Olswold, Curtis
creator: Lindor, Noralane M.
creator: Pankratz, Vernon S.
creator: Szabo, Csilla I.
creator: Lincoln, Anne
creator: Jacobs, Lauren
creator: Corines, Marina
creator: Robson, Mark
creator: Vijai, Joseph
creator: Berger, Andreas
creator: Fink-Retter, Anneliese
creator: Singer, Christian F.
creator: Rappaport, Christine
creator: Geschwantler Kaulich, Daphne
creator: Pfeiler, Georg
creator: Tea, Muy-Kheng
creator: Greene, Mark H.
creator: Mai, Phuong L.
creator: Rennert, Gad
creator: Imyanitov, Evgeny N.
creator: Mulligan, Anna Marie
creator: Glendon, Gord
creator: Andrulis, Irene L
creator: Tchatchou, Sandrine
creator: Ewart Toland, Amanda
creator: Sokilde Pedersen, Inge
creator: Thomassen, Mads
creator: Kruse, Torben A.
creator: Jensen, Uffe Birk
creator: Caligo, Maria A.
creator: Friedman, Eitan
creator: Zidan, Jamal
creator: Laitman, Yael
creator: Lindblom, Annika
creator: Melin, Beatrice
creator: Arver, Brita
creator: Loman, Niklas
creator: Rosenquist, Richard
creator: Olopade, Olufunmilayo I.
creator: Nussbaum, Robert L.
creator: Ramus, Susan J.
creator: Nathanson, Katherine L.
creator: Domchek, Susan M.
creator: Rebbeck, Timothy R.
creator: Arun, Banu K.
creator: Mitchell, Gillian
creator: Karlan, Beth Y.
creator: Lester, Jenny
creator: Orsulic, Sandra
creator: Stoppa-Lyonnet, Dominique
creator: Thomas, Gilles
creator: Simard, Jacques
creator: Couch, Fergus J.
creator: Offit, Kenneth
creator: Easton, Douglas F.
creator: Chenevix-Trench, Georgia
creator: Antoniou, Antonis C.
creator: Mazoyer, Sylvie
creator: Phelan, Catherine M.
creator: Sinilnikova, Olga M.
creator: Cox, David G.
subject: ddc-610
subject: 610 Medical sciences Medicine
description: 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.  
publisher: BioMed Central
date: 2015
type: Article
type: info:eu-repo/semantics/article
type: NonPeerReviewed
format: application/pdf
identifier: https://archiv.ub.uni-heidelberg.de/volltextserverhttps://archiv.ub.uni-heidelberg.de/volltextserver/19471/1/13058_2015_Article_567.pdf
identifier: DOI:
identifier: urn:nbn:de:bsz:16-heidok-194719
identifier:   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.  (2015) An original phylogenetic approach identified mitochondrial haplogroup T1a1 as inversely associated with breast cancer risk in BRCA2 mutation carriers.  Breast Cancer Research, 17 (61).  pp. 1-15.  ISSN 1465-542X     
relation: https://archiv.ub.uni-heidelberg.de/volltextserver/19471/
rights: info:eu-repo/semantics/openAccess
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language: eng