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 Beth, 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 V. O., Osorio, Ana, Benitez, Javier, Andres Conejero, Raquel, 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, Hansjoerg, Kast, Karin, Rhiem, Kerstin, Ditsch, Nina, Arnold, Norbert, Varon-Mateeva, Raymonda, Schmutzler, Rita K., Preisler-Adams, Sabine, Markov, Nadja Bogdanova, Wang-Gohrke, Shan, de Pauw, Antoine, Lefol, Cedrick, Lasset, Christine, Leroux, Dominique, Rouleau, Etienne, Damiola, Francesca, Dreyfus, Helene, Barjhoux, Laure, Golmard, Lisa, Uhrhammer, Nancy, Bonadona, Valerie, Sornin, Valerie, Bignon, Yves-Jean, Carter, Jonathan, Van Le, Linda, Piedmonte, Marion, DiSilvestro, Paul A., de la Hoya, Miguel, Caldes, Trinidad, Nevanlinna, Heli, Aittomaki, Kristiina, Jager, Agnes, van den Ouweland, Ans M. W., Kets, Carolien M., Aalfs, Cora M., van Leeuwen, Flora E., Hogervorst, Frans B. L., Meijers-Heijboer, Hanne E. J., Oosterwijk, Jan C., van Roozendaal, Kees E. P., Rookus, Matti A., Devilee, Peter, van der Luijt, Rob B., Olah, Edith, Diez, Orland, Teule, Alex, Lazaro, Conxi, Blanco, Ignacio, Del Valle, Jesus, 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, Kaulich, Daphne Geschwantler, 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, Toland, Amanda Ewart, Pedersen, Inge Sokilde, 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. and 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 1: . doi:10.1186/s13058-015-0567-2

Attached Files (Some files may be inaccessible until you login with your UQ eSpace credentials)
Name Description MIMEType Size Downloads
Spurdle_Amanda_authoraffil_staffdata.pdf Spurdle_Amanda_authoraffil_staffdata.pdf application/pdf 140.43KB 0

Author Blein, Sophie
Bardel, Claire
Danjean, Vincent
McGuffog, Lesley
Healey, Sue
Barrowdale, Daniel
Lee, Andrew
Dennis, Joe
Kuchenbaecker, Karoline B.
Soucy, Penny
Terry, Mary Beth
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 V. O.
Osorio, Ana
Benitez, Javier
Andres Conejero, Raquel
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, Hansjoerg
Kast, Karin
Rhiem, Kerstin
Ditsch, Nina
Arnold, Norbert
Varon-Mateeva, Raymonda
Schmutzler, Rita K.
Preisler-Adams, Sabine
Markov, Nadja Bogdanova
Wang-Gohrke, Shan
de Pauw, Antoine
Lefol, Cedrick
Lasset, Christine
Leroux, Dominique
Rouleau, Etienne
Damiola, Francesca
Dreyfus, Helene
Barjhoux, Laure
Golmard, Lisa
Uhrhammer, Nancy
Bonadona, Valerie
Sornin, Valerie
Bignon, Yves-Jean
Carter, Jonathan
Van Le, Linda
Piedmonte, Marion
DiSilvestro, Paul A.
de la Hoya, Miguel
Caldes, Trinidad
Nevanlinna, Heli
Aittomaki, Kristiina
Jager, Agnes
van den Ouweland, Ans M. W.
Kets, Carolien M.
Aalfs, Cora M.
van Leeuwen, Flora E.
Hogervorst, Frans B. L.
Meijers-Heijboer, Hanne E. J.
Oosterwijk, Jan C.
van Roozendaal, Kees E. P.
Rookus, Matti A.
Devilee, Peter
van der Luijt, Rob B.
Olah, Edith
Diez, Orland
Teule, Alex
Lazaro, Conxi
Blanco, Ignacio
Del Valle, Jesus
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
Kaulich, Daphne Geschwantler
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
Toland, Amanda Ewart
Pedersen, Inge Sokilde
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.
Title An original phylogenetic approach identified mitochondrial haplogroup T1a1 as inversely associated with breast cancer risk in BRCA2 mutation carriers
Journal name Breast Cancer Research   Check publisher's open access policy
ISSN 1465-542X
1465-5411
Publication date 2015-04-25
Sub-type Article (original research)
DOI 10.1186/s13058-015-0567-2
Open Access Status DOI
Volume 17
Issue 1
Total pages 15
Place of publication London, United Kingdom
Publisher BioMed Central
Language eng
Formatted 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.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2016 Collection
School of Medicine Publications
UQ Diamantina Institute Publications
 
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 4 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 5 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Sat, 28 Nov 2015, 05:17:17 EST by System User on behalf of Scholarly Communication and Digitisation Service