Abstract
| Original language | English |
|---|---|
| Article number | 61 |
| Pages (from-to) | 61 |
| Journal | Breast Cancer Research |
| Volume | 17 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 2015 |
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In: Breast Cancer Research, Vol. 17, No. 1, 61, 2015, p. 61.
Research output: Contribution to journal › Article › Academic › peer-review
TY - JOUR
T1 - An original phylogenetic approach identified mitochondrial haplogroup T1a1 as inversely associated with breast cancer risk in BRCA2 mutation carriers
AU - Blein, Sophie
AU - Bardel, Claire
AU - Danjean, Vincent
AU - McGuffog, Lesley
AU - Healey, Sue
AU - Barrowdale, Daniel
AU - Lee, Andrew
AU - Dennis, Joe
AU - Kuchenbaecker, Karoline B.
AU - Soucy, Penny
AU - Terry, Mary Beth
AU - Chung, Wendy K.
AU - Goldgar, David E.
AU - Buys, Saundra S.
AU - Janavicius, Ramunas
AU - Tihomirova, Laima
AU - Tung, Nadine
AU - Dorfling, Cecilia M.
AU - van Rensburg, Elizabeth J.
AU - Neuhausen, Susan L.
AU - Ding, Yuan Chun
AU - Gerdes, Anne-Marie
AU - Ejlertsen, Bent
AU - Nielsen, Finn C.
AU - Hansen, Thomas vO
AU - Osorio, Ana
AU - Benitez, Javier
AU - Conejero, Raquel Andrés
AU - Segota, Ena
AU - Weitzel, Jeffrey N.
AU - Thelander, Margo
AU - Peterlongo, Paolo
AU - Radice, Paolo
AU - Pensotti, Valeria
AU - Dolcetti, Riccardo
AU - Bonanni, Bernardo
AU - Peissel, Bernard
AU - Zaffaroni, Daniela
AU - Scuvera, Giulietta
AU - Manoukian, Siranoush
AU - Varesco, Liliana
AU - Capone, Gabriele L.
AU - Papi, Laura
AU - Ottini, Laura
AU - Yannoukakos, Drakoulis
AU - Konstantopoulou, Irene
AU - Garber, Judy
AU - Hamann, Ute
AU - Donaldson, Alan
AU - Brady, Angela
AU - Brewer, Carole
AU - Foo, Claire
AU - Evans, D. Gareth
AU - Frost, Debra
AU - Eccles, Diana
AU - Douglas, Fiona
AU - Cook, Jackie
AU - Adlard, Julian
AU - Barwell, Julian
AU - Walker, Lisa
AU - Izatt, Louise
AU - Side, Lucy E.
AU - Kennedy, M. John
AU - Tischkowitz, Marc
AU - Rogers, Mark T.
AU - Porteous, Mary E.
AU - Morrison, Patrick J.
AU - Platte, Radka
AU - Eeles, Ros
AU - Davidson, Rosemarie
AU - Hodgson, Shirley
AU - Cole, Trevor
AU - Godwin, Andrew K.
AU - Isaacs, Claudine
AU - Claes, Kathleen
AU - de Leeneer, Kim
AU - Meindl, Alfons
AU - Gehrig, Andrea
AU - Wappenschmidt, Barbara
AU - Sutter, Christian
AU - Engel, Christoph
AU - Niederacher, Dieter
AU - Steinemann, Doris
AU - Plendl, Hansjoerg
AU - Kast, Karin
AU - Rhiem, Kerstin
AU - Ditsch, Nina
AU - Arnold, Norbert
AU - Varon-Mateeva, Raymonda
AU - Schmutzler, Rita K.
AU - Preisler-Adams, Sabine
AU - Markov, Nadja Bogdanova
AU - Wang-Gohrke, Shan
AU - de Pauw, Antoine
AU - Lefol, Cédrick
AU - Lasset, Christine
AU - Leroux, Dominique
AU - Rouleau, Etienne
AU - Damiola, Francesca
AU - Dreyfus, Hélène
AU - Barjhoux, Laure
AU - Golmard, Lisa
AU - Uhrhammer, Nancy
AU - Bonadona, Valérie
AU - Sornin, Valérie
AU - Bignon, Yves-Jean
AU - Carter, Jonathan
AU - van Le, Linda
AU - Piedmonte, Marion
AU - DiSilvestro, Paul A.
AU - de la Hoya, Miguel
AU - Caldes, Trinidad
AU - Nevanlinna, Heli
AU - Aittomäki, Kristiina
AU - Jager, Agnes
AU - van den Ouweland, Ans Mw
AU - Kets, Carolien M.
AU - Aalfs, Cora M.
AU - van Leeuwen, Flora E.
AU - Hogervorst, Frans Bl
AU - Meijers-Heijboer, Hanne Ej
AU - Oosterwijk, Jan C.
AU - van Roozendaal, Kees Ep
AU - Rookus, Matti A.
AU - Devilee, Peter
AU - van der Luijt, Rob B.
AU - Olah, Edith
AU - Diez, Orland
AU - Teulé, Alex
AU - Lazaro, Conxi
AU - Blanco, Ignacio
AU - del Valle, Jesús
AU - Jakubowska, Anna
AU - Sukiennicki, Grzegorz
AU - Gronwald, Jacek
AU - Lubinski, Jan
AU - Durda, Katarzyna
AU - Jaworska-Bieniek, Katarzyna
AU - Agnarsson, Bjarni A.
AU - Maugard, Christine
AU - Amadori, Alberto
AU - Montagna, Marco
AU - Teixeira, Manuel R.
AU - Spurdle, Amanda B.
AU - Foulkes, William
AU - Olswold, Curtis
AU - Lindor, Noralane M.
AU - Pankratz, Vernon S.
AU - Szabo, Csilla I.
AU - Lincoln, Anne
AU - Jacobs, Lauren
AU - Corines, Marina
AU - Robson, Mark
AU - Vijai, Joseph
AU - Berger, Andreas
AU - Fink-Retter, Anneliese
AU - Singer, Christian F.
AU - Rappaport, Christine
AU - Kaulich, Daphne Geschwantler
AU - Pfeiler, Georg
AU - tea, Muy-Kheng
AU - Greene, Mark H.
AU - Mai, Phuong L.
AU - Rennert, Gad
AU - Imyanitov, Evgeny N.
AU - Mulligan, Anna Marie
AU - Glendon, Gord
AU - Andrulis, Irene L.
AU - Tchatchou, Sandrine
AU - Toland, Amanda Ewart
AU - Pedersen, Inge Sokilde
AU - Thomassen, Mads
AU - Kruse, Torben A.
AU - Jensen, Uffe Birk
AU - Caligo, Maria A.
AU - Friedman, Eitan
AU - Zidan, Jamal
AU - Laitman, Yael
AU - Lindblom, Annika
AU - Melin, Beatrice
AU - Arver, Brita
AU - Loman, Niklas
AU - Rosenquist, Richard
AU - Olopade, Olufunmilayo I.
AU - Nussbaum, Robert L.
AU - Ramus, Susan J.
AU - Nathanson, Katherine L.
AU - Domchek, Susan M.
AU - Rebbeck, Timothy R.
AU - Arun, Banu K.
AU - Mitchell, Gillian
AU - Karlan, Beth Y.
AU - Lester, Jenny
AU - Orsulic, Sandra
AU - Stoppa-Lyonnet, Dominique
AU - Thomas, Gilles
AU - Simard, Jacques
AU - Couch, Fergus J.
AU - Offit, Kenneth
AU - Easton, Douglas F.
AU - Chenevix-Trench, Georgia
AU - Antoniou, Antonis C.
AU - Mazoyer, Sylvie
AU - Phelan, Catherine M.
AU - Sinilnikova, Olga M.
AU - Cox, David G.
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
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
U2 - https://doi.org/10.1186/s13058-015-0567-2
DO - https://doi.org/10.1186/s13058-015-0567-2
M3 - Article
C2 - 25925750
SN - 1465-5411
VL - 17
SP - 61
JO - Breast Cancer Research
JF - Breast Cancer Research
IS - 1
M1 - 61
ER -