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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2015-12

AUTHORS

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

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. More... »

PAGES

61

References to SciGraph publications

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  • Journal

    TITLE

    Breast Cancer Research

    ISSUE

    1

    VOLUME

    17

    Author Affiliations

  • Claude Bernard University Lyon 1
  • Biometry and Evolutionary Biology Laboratory
  • Grenoble Computer Science Laboratory
  • University of Cambridge
  • QIMR Berghofer Medical Research Institute
  • Université Laval
  • Columbia University
  • University of Utah
  • Cancer Prevention Institute of California
  • Vilnius University Hospital Santariskiu Klinikos
  • Latvian Biomedical Research and Study Centre
  • Beth Israel Deaconess Medical Center
  • University of Pretoria
  • City Of Hope National Medical Center
  • Centre for Biomedical Network Research on Rare Diseases
  • Hospital Clínico Universitario Lozano Blesa
  • FIRC Institute of Molecular Oncology
  • Istituto Nazionale dei Tumori
  • Centro di Riferimento Oncologico
  • European Institute of Oncology
  • University of Florence
  • Sapienza University of Rome
  • Aristotle University of Thessaloniki
  • National Centre of Scientific Research Demokritos
  • Dana–Farber Cancer Institute
  • German Cancer Research Center
  • St Michael's Hospital
  • Royal Devon and Exeter Hospital
  • Liverpool Womens NHS Foundation Trust
  • Manchester University NHS Foundation Trust
  • Sheffield Children's Hospital
  • Leicester Royal Infirmary
  • Churchill Hospital
  • Guy's Hospital
  • Great Ormond Street Hospital for Children NHS Foundation Trust
  • St. James's Hospital
  • Addenbrooke's Hospital
  • University Hospital of Wales
  • Western General Hospital
  • Belfast City Hospital
  • National Health Service
  • Royal Hospital for Sick Children
  • St George's, University of London
  • University of Kansas Medical Center
  • Ghent University Hospital
  • University of Würzburg
  • University of Cologne
  • University Hospital Heidelberg
  • Leipzig University
  • Hannover Medical School
  • University Hospital Schleswig-Holstein
  • Virchow Klinikum
  • University Hospital Münster
  • University Hospital Ulm
  • Institute Curie
  • Centre Léon Bérard
  • Joseph Fourier University
  • Hôpital René Huguenin
  • Cancer Center of Lyon
  • Chris O’Brien Lifehouse
  • University of North Carolina at Chapel Hill
  • Roswell Park Cancer Institute
  • Women & Infants Hospital of Rhode Island
  • Helsinki University Central Hospital
  • Erasmus University Medical Center
  • Radboud University Nijmegen Medical Centre
  • Academic Medical Center
  • Antoni van Leeuwenhoek Hospital
  • VU University Medical Center
  • University of Groningen
  • Maastricht University Medical Centre
  • Leiden University Medical Center
  • University Medical Center Utrecht
  • National Institute of Oncology
  • Hospital Universitari Vall d'Hebron
  • Duran i Reynals Hospital
  • Pomeranian Medical University
  • Hôpital Civil, Strasbourg
  • Istituto Oncologico Veneto
  • University of Porto
  • McGill University
  • Mayo Clinic
  • Mayo Clinic
  • National Human Genome Research Institute
  • Memorial Sloan Kettering Cancer Center
  • National Institutes of Health
  • Technion – Israel Institute of Technology
  • Institute of Oncology NN Petrov
  • St. Michael's Hospital
  • Lunenfeld-Tanenbaum Research Institute
  • University of Toronto
  • James Cancer Hospital
  • Aalborg Hospital
  • Odense University Hospital
  • Aarhus University Hospital
  • Sheba Medical Center
  • Karolinska University Hospital
  • Umeå University
  • Skåne University Hospital
  • Uppsala University
  • University of California, San Francisco
  • University of Southern California
  • University of Pennsylvania
  • The University of Texas MD Anderson Cancer Center
  • University of Melbourne
  • Cedars-Sinai Medical Center
  • Paris Descartes University
  • Moffitt Cancer Center
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1186/s13058-015-0567-2

    DOI

    http://dx.doi.org/10.1186/s13058-015-0567-2

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1045881923

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/25925750


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