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

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

doi:10.1186/s13058-015-0567-2

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

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

Producció científica: Contribució a revista › Article › Recerca › Avaluat per experts

30 Cites (Scopus)

Resum

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. 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. 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. 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. The online version of this article (doi:10.1186/s13058-015-0567-2) contains supplementary material, which is available to authorized users

Idioma original	Anglès
Revista	Breast Cancer Research
Volum	17
DOIs	https://doi.org/10.1186/s13058-015-0567-2
Estat de la publicació	Publicada - 2015

SDG de les Nacions Unides

Aquest resultat contribueix als següents objectius de desenvolupament sostenible.

Accés al document

10.1186/s13058-015-0567-2

https://ddd.uab.cat/record/254355

Com citar-ho

Garber, J., Sutter, C., Wang-Gohrke, S., Bignon, Y.-J., Peissel, B., Caligo, M., van der Luijt, R. B., Brewer, C., Montagna, M., Manoukian, S., Janavicius, R., Ramus, S. J., Terry, M. B., Pankratz, V. S., Hansen, T. V. O., Kets, C. M., Aittomäki, K., Barwell, J., Preisler-Adams, S., ... Ding, Y. C. (2015). An original phylogenetic approach identified mitochondrial haplogrou,p T1a1 as inversely associated with breast cancer risk in BRCA2 mutation carriers. Breast Cancer Research, 17. https://doi.org/10.1186/s13058-015-0567-2

@article{f3d3e4b2c5534f77bde8a3ecbc525492,

title = "An original phylogenetic approach identified mitochondrial haplogrou,p T1a1 as inversely associated with breast cancer risk in BRCA2 mutation carriers",

abstract = "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. 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. 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. 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. The online version of this article (doi:10.1186/s13058-015-0567-2) contains supplementary material, which is available to authorized users",

author = "Judy Garber and Christian Sutter and Shan Wang-Gohrke and Yves-Jean Bignon and Bernard Peissel and Maria Caligo and {van der Luijt}, {Rob B.} and Carole Brewer and Marco Montagna and Siranoush Manoukian and Ramunas Janavicius and Ramus, {Susan J.} and Terry, {Mary Beth} and Pankratz, {Vernon S.} and Hansen, {Thomas V. O.} and Kets, {Carolien M.} and Kristiina Aittom{\"a}ki and Julian Barwell and Sabine Preisler-Adams and Ana Osorio and Christine Maugard and {De la Hoya}, Miguel and Katarzyna Jaworska-Bieniek and Val{\'e}rie Bonadona and Agnes Jager and Alfons Meindl and Sophie Blein and Rebbeck, {Timothy R.} and Godwin, {Andrew K.} and Jonathan Carter and Jan Lubinski and Szabo, {Csilla I} and Jamal Zidan and Greene, {Mark H.} and Lisa Walker and William Foulkes and Fiona Douglas and Francesca Damiola and Trevor Cole and DiSilvestro, {Paul A.} and Paolo Peterlongo and Muy-Kheng Tea and Alex Teul{\'e} and Jenny Lester and Jacques Simard and Aalfs, {Cora M.} and Paolo Radice and Sandrine Tchatchou and Pedersen, {Inge Sokilde} and Lisa Golmard and Rosalind Eeles and Couch, {Fergus J.} and Daniel Barrowdale and Andrulis, {Irene L.} and Teixeira, {Manuel R.} and Marion Piedmonte and Georgia Chenevix-Trench and Doris Steinemann and Trinidad Caldes and Marina Corines and Angela Brady and Eccles, {Diana M} and Drakoulis Yannoukakos and Goldgar, {David E.} and Val{\'e}rie Sornin and Niklas Loman and Lindor, {Noralane M.} and Hogervorst, {Frans B. L.} and Richard Rosenquist and Kruse, {Torben A.} and Porteous, {Mary E.} and {van den Ouweland}, {Ans M. W.} and Kenneth Offit and Bernardo Bonanni and Gord Glendon and Rookus, {Matti A.} and Mark Robson and Radka Platte and Brita Arver and Dieter Niederacher and Kennedy, {M. John} and H{\'e}l{\`e}ne Dreyfus and Anna Jakubowska and Claire Foo and Valeria Pensotti and Riccardo Dolcetti and Saundra Buys and Kaulich, {Daphne Geschwantler} and Liliana Varesco and Lesley McGuffog and {Blanco Guillermo}, Ignacio and Sandra Orsulic and Nina Ditsch and Schmutzler, {Rita K.} and Toland, {Amanda Ewart} and Christine Rappaport and Claudine Isaacs and {van Roozendaal}, {Kees E. P.} and Giulietta Scuvera and Spurdle, {Amanda B.} and Mulligan, {Anna Marie} and Margo Thelander and Nielsen, {Finn C.} and Georg Pfeiler and Curtis Olswold and Cox, {David G.} and Orland Diez and Morrison, {Patrick J.} and Edith Olah and Meijers-Heijboer, {Hanne E. J.} and Jensen, {Uffe Birk} and Shirley Hodgson and Jacek Gronwald and Dominique Stoppa-Lyonnet and Hansjoerg Plendl and Rosemarie Davidson and Karin Kast and {Andr{\'e}s Conejero}, Raquel and Kuchenbaecker, {Karoline B.} and Gilles Thomas and Annika Lindblom and {Van Le}, Linda and Anne-Marie Gerdes and Bent Ejlertsen and Daniela Zaffaroni and Dominique Leroux and Javier Benitez and Gareth Evans and {van Leeuwen}, {Flora E.} and {De Pauw}, Antoine and Andreas Berger and {De Leeneer}, Kim and Agnarsson, {Bjarni A.} and Vincent Danjean and {Del Valle}, Jes{\'u}s and Kathleen Claes and Lauren Jacobs and Kerstin Rhiem and Gillian Mitchell and Singer, {Christian F.} and Domchek, {Susan M.} and Katarzyna Durda and Conxi Lazaro and C{\'e}drick Lefol and Oosterwijk, {Jan C.} and Sinilnikova, {Olga M.} and Alan Donaldson and Capone, {Gabriele L.} and Karlan, {Beth Y} and Olopade, {Olufunmilayo I} and Arun, {Banu K.} and Alberto Amadori and Etienne Rouleau and Sue Healey and Julian Adlard and Grzegorz Sukiennicki and Mads Thomassen and Andrew Lee and Laura Papi and Antoniou, {Antonis C.} and Weitzel, {Jeffrey N.} and Dorfling, {Cecilia M.} and Easton, {Douglas F.} and Joe Dennis and Sylvie Mazoyer and Laima Tihomirova and Phelan, {Catherine M.} and {van Rensburg}, {Elizabeth J.} and Ute Hamann and Mai, {Phuong L.} and Yael Laitman and Anne Lincoln and Norbert Arnold and Markov, {Nadja Bogdanova} and Raymonda Varon-Mateeva and Irene Konstantopoulou and Debra Frost and Barbara Wappenschmidt and Claire Bardel and Andrea Gehrig and Nathanson, {Katherine L.} and Beatrice Melin and Ena Segota and Louise Izatt and Penny Soucy and Jackie Cook and Side, {Lucy E.} and Marc Tischkowitz and Peter Devilee and Nancy Uhrhammer and Nadine Tung and Wendy Chung and Rogers, {Mark T.} and Imyanitov, {Evgeny N.} and Joseph Vijai and Anneliese Fink-Retter and Nussbaum, {Robert L.} and Christine Lasset and Laure Barjhoux and Eitan Friedman and Heli Nevanlinna and Laura Ottini and Neuhausen, {Susan L.} and Christoph Engel and Gad Rennert and Ding, {Yuan Chun}",

year = "2015",

doi = "10.1186/s13058-015-0567-2",

language = "English",

volume = "17",

}

Garber, J, Sutter, C, Wang-Gohrke, S, Bignon, Y-J, Peissel, B, Caligo, M, van der Luijt, RB, Brewer, C, Montagna, M, Manoukian, S, Janavicius, R, Ramus, SJ, Terry, MB, Pankratz, VS, Hansen, TVO, Kets, CM, Aittomäki, K, Barwell, J, Preisler-Adams, S, Osorio, A, Maugard, C, De la Hoya, M, Jaworska-Bieniek, K, Bonadona, V, Jager, A, Meindl, A, Blein, S, Rebbeck, TR, Godwin, AK, Carter, J, Lubinski, J, Szabo, CI, Zidan, J, Greene, MH, Walker, L, Foulkes, W, Douglas, F, Damiola, F, Cole, T, DiSilvestro, PA, Peterlongo, P, Tea, M-K, Teulé, A, Lester, J, Simard, J, Aalfs, CM, Radice, P, Tchatchou, S, Pedersen, IS, Golmard, L, Eeles, R, Couch, FJ, Barrowdale, D, Andrulis, IL, Teixeira, MR, Piedmonte, M, Chenevix-Trench, G, Steinemann, D, Caldes, T, Corines, M, Brady, A, Eccles, DM, Yannoukakos, D, Goldgar, DE, Sornin, V, Loman, N, Lindor, NM, Hogervorst, FBL, Rosenquist, R, Kruse, TA, Porteous, ME, van den Ouweland, AMW, Offit, K, Bonanni, B, Glendon, G, Rookus, MA, Robson, M, Platte, R, Arver, B, Niederacher, D, Kennedy, MJ, Dreyfus, H, Jakubowska, A, Foo, C, Pensotti, V, Dolcetti, R, Buys, S, Kaulich, DG, Varesco, L, McGuffog, L, Blanco Guillermo, I, Orsulic, S, Ditsch, N, Schmutzler, RK, Toland, AE, Rappaport, C, Isaacs, C, van Roozendaal, KEP, Scuvera, G, Spurdle, AB, Mulligan, AM, Thelander, M, Nielsen, FC, Pfeiler, G, Olswold, C, Cox, DG, Diez, O, Morrison, PJ, Olah, E, Meijers-Heijboer, HEJ, Jensen, UB, Hodgson, S, Gronwald, J, Stoppa-Lyonnet, D, Plendl, H, Davidson, R, Kast, K, Andrés Conejero, R, Kuchenbaecker, KB, Thomas, G, Lindblom, A, Van Le, L, Gerdes, A-M, Ejlertsen, B, Zaffaroni, D, Leroux, D, Benitez, J, Evans, G, van Leeuwen, FE, De Pauw, A, Berger, A, De Leeneer, K, Agnarsson, BA, Danjean, V, Del Valle, J, Claes, K, Jacobs, L, Rhiem, K, Mitchell, G, Singer, CF, Domchek, SM, Durda, K, Lazaro, C, Lefol, C, Oosterwijk, JC, Sinilnikova, OM, Donaldson, A, Capone, GL, Karlan, BY, Olopade, OI, Arun, BK, Amadori, A, Rouleau, E, Healey, S, Adlard, J, Sukiennicki, G, Thomassen, M, Lee, A, Papi, L, Antoniou, AC, Weitzel, JN, Dorfling, CM, Easton, DF, Dennis, J, Mazoyer, S, Tihomirova, L, Phelan, CM, van Rensburg, EJ, Hamann, U, Mai, PL, Laitman, Y, Lincoln, A, Arnold, N, Markov, NB, Varon-Mateeva, R, Konstantopoulou, I, Frost, D, Wappenschmidt, B, Bardel, C, Gehrig, A, Nathanson, KL, Melin, B, Segota, E, Izatt, L, Soucy, P, Cook, J, Side, LE, Tischkowitz, M, Devilee, P, Uhrhammer, N, Tung, N, Chung, W, Rogers, MT, Imyanitov, EN, Vijai, J, Fink-Retter, A, Nussbaum, RL, Lasset, C, Barjhoux, L, Friedman, E, Nevanlinna, H, Ottini, L, Neuhausen, SL, Engel, C, Rennert, G & Ding, YC 2015, 'An original phylogenetic approach identified mitochondrial haplogrou,p T1a1 as inversely associated with breast cancer risk in BRCA2 mutation carriers', Breast Cancer Research, vol. 17. https://doi.org/10.1186/s13058-015-0567-2

TY - JOUR

T1 - An original phylogenetic approach identified mitochondrial haplogrou,p T1a1 as inversely associated with breast cancer risk in BRCA2 mutation carriers

AU - Garber, Judy

AU - Sutter, Christian

AU - Wang-Gohrke, Shan

AU - Bignon, Yves-Jean

AU - Peissel, Bernard

AU - Caligo, Maria

AU - van der Luijt, Rob B.

AU - Brewer, Carole

AU - Montagna, Marco

AU - Manoukian, Siranoush

AU - Janavicius, Ramunas

AU - Ramus, Susan J.

AU - Terry, Mary Beth

AU - Pankratz, Vernon S.

AU - Hansen, Thomas V. O.

AU - Kets, Carolien M.

AU - Aittomäki, Kristiina

AU - Barwell, Julian

AU - Preisler-Adams, Sabine

AU - Osorio, Ana

AU - Maugard, Christine

AU - De la Hoya, Miguel

AU - Jaworska-Bieniek, Katarzyna

AU - Bonadona, Valérie

AU - Jager, Agnes

AU - Meindl, Alfons

AU - Blein, Sophie

AU - Rebbeck, Timothy R.

AU - Godwin, Andrew K.

AU - Carter, Jonathan

AU - Lubinski, Jan

AU - Szabo, Csilla I

AU - Zidan, Jamal

AU - Greene, Mark H.

AU - Walker, Lisa

AU - Foulkes, William

AU - Douglas, Fiona

AU - Damiola, Francesca

AU - Cole, Trevor

AU - DiSilvestro, Paul A.

AU - Peterlongo, Paolo

AU - Tea, Muy-Kheng

AU - Teulé, Alex

AU - Lester, Jenny

AU - Simard, Jacques

AU - Aalfs, Cora M.

AU - Radice, Paolo

AU - Tchatchou, Sandrine

AU - Pedersen, Inge Sokilde

AU - Golmard, Lisa

AU - Eeles, Rosalind

AU - Couch, Fergus J.

AU - Barrowdale, Daniel

AU - Andrulis, Irene L.

AU - Teixeira, Manuel R.

AU - Piedmonte, Marion

AU - Chenevix-Trench, Georgia

AU - Steinemann, Doris

AU - Caldes, Trinidad

AU - Corines, Marina

AU - Brady, Angela

AU - Eccles, Diana M

AU - Yannoukakos, Drakoulis

AU - Goldgar, David E.

AU - Sornin, Valérie

AU - Loman, Niklas

AU - Lindor, Noralane M.

AU - Hogervorst, Frans B. L.

AU - Rosenquist, Richard

AU - Kruse, Torben A.

AU - Porteous, Mary E.

AU - van den Ouweland, Ans M. W.

AU - Offit, Kenneth

AU - Bonanni, Bernardo

AU - Glendon, Gord

AU - Rookus, Matti A.

AU - Robson, Mark

AU - Platte, Radka

AU - Arver, Brita

AU - Niederacher, Dieter

AU - Kennedy, M. John

AU - Dreyfus, Hélène

AU - Jakubowska, Anna

AU - Foo, Claire

AU - Pensotti, Valeria

AU - Dolcetti, Riccardo

AU - Buys, Saundra

AU - Kaulich, Daphne Geschwantler

AU - Varesco, Liliana

AU - McGuffog, Lesley

AU - Blanco Guillermo, Ignacio

AU - Orsulic, Sandra

AU - Ditsch, Nina

AU - Schmutzler, Rita K.

AU - Toland, Amanda Ewart

AU - Rappaport, Christine

AU - Isaacs, Claudine

AU - van Roozendaal, Kees E. P.

AU - Scuvera, Giulietta

AU - Spurdle, Amanda B.

AU - Mulligan, Anna Marie

AU - Thelander, Margo

AU - Nielsen, Finn C.

AU - Pfeiler, Georg

AU - Olswold, Curtis

AU - Cox, David G.

AU - Diez, Orland

AU - Morrison, Patrick J.

AU - Olah, Edith

AU - Meijers-Heijboer, Hanne E. J.

AU - Jensen, Uffe Birk

AU - Hodgson, Shirley

AU - Gronwald, Jacek

AU - Stoppa-Lyonnet, Dominique

AU - Plendl, Hansjoerg

AU - Davidson, Rosemarie

AU - Kast, Karin

AU - Andrés Conejero, Raquel

AU - Kuchenbaecker, Karoline B.

AU - Thomas, Gilles

AU - Lindblom, Annika

AU - Van Le, Linda

AU - Gerdes, Anne-Marie

AU - Ejlertsen, Bent

AU - Zaffaroni, Daniela

AU - Leroux, Dominique

AU - Benitez, Javier

AU - Evans, Gareth

AU - van Leeuwen, Flora E.

AU - De Pauw, Antoine

AU - Berger, Andreas

AU - De Leeneer, Kim

AU - Agnarsson, Bjarni A.

AU - Danjean, Vincent

AU - Del Valle, Jesús

AU - Claes, Kathleen

AU - Jacobs, Lauren

AU - Rhiem, Kerstin

AU - Mitchell, Gillian

AU - Singer, Christian F.

AU - Domchek, Susan M.

AU - Durda, Katarzyna

AU - Lazaro, Conxi

AU - Lefol, Cédrick

AU - Oosterwijk, Jan C.

AU - Sinilnikova, Olga M.

AU - Donaldson, Alan

AU - Capone, Gabriele L.

AU - Karlan, Beth Y

AU - Olopade, Olufunmilayo I

AU - Arun, Banu K.

AU - Amadori, Alberto

AU - Rouleau, Etienne

AU - Healey, Sue

AU - Adlard, Julian

AU - Sukiennicki, Grzegorz

AU - Thomassen, Mads

AU - Lee, Andrew

AU - Papi, Laura

AU - Antoniou, Antonis C.

AU - Weitzel, Jeffrey N.

AU - Dorfling, Cecilia M.

AU - Easton, Douglas F.

AU - Dennis, Joe

AU - Mazoyer, Sylvie

AU - Tihomirova, Laima

AU - Phelan, Catherine M.

AU - van Rensburg, Elizabeth J.

AU - Hamann, Ute

AU - Mai, Phuong L.

AU - Laitman, Yael

AU - Lincoln, Anne

AU - Arnold, Norbert

AU - Markov, Nadja Bogdanova

AU - Varon-Mateeva, Raymonda

AU - Konstantopoulou, Irene

AU - Frost, Debra

AU - Wappenschmidt, Barbara

AU - Bardel, Claire

AU - Gehrig, Andrea

AU - Nathanson, Katherine L.

AU - Melin, Beatrice

AU - Segota, Ena

AU - Izatt, Louise

AU - Soucy, Penny

AU - Cook, Jackie

AU - Side, Lucy E.

AU - Tischkowitz, Marc

AU - Devilee, Peter

AU - Uhrhammer, Nancy

AU - Tung, Nadine

AU - Chung, Wendy

AU - Rogers, Mark T.

AU - Imyanitov, Evgeny N.

AU - Vijai, Joseph

AU - Fink-Retter, Anneliese

AU - Nussbaum, Robert L.

AU - Lasset, Christine

AU - Barjhoux, Laure

AU - Friedman, Eitan

AU - Nevanlinna, Heli

AU - Ottini, Laura

AU - Neuhausen, Susan L.

AU - Engel, Christoph

AU - Rennert, Gad

AU - Ding, Yuan Chun

PY - 2015

Y1 - 2015

N2 - 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. 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. 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. 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. The online version of this article (doi:10.1186/s13058-015-0567-2) contains supplementary material, which is available to authorized users

AB - 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. 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. 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. 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. The online version of this article (doi:10.1186/s13058-015-0567-2) contains supplementary material, which is available to authorized users

U2 - 10.1186/s13058-015-0567-2

DO - 10.1186/s13058-015-0567-2

M3 - Article

C2 - 25925750

SN - 1465-542X

VL - 17

JO - Breast Cancer Research

JF - Breast Cancer Research

ER -

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

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