Journal
BREAST CANCER RESEARCH
Volume 17, Issue -, Pages -Publisher
BMC
DOI: 10.1186/s13058-015-0567-2
Keywords
-
Categories
Funding
- European Commission Seventh Framework Program [223175: HEALTH-F2-2009-223175]
- Cancer Research UK [C12292/A11174, C1287/A10118, C1287/A11990, C5047/A8385]
- National Health and Medical Research Council (NHMRC) program
- National Health and Medical Research Council (NHMRC)
- American Cancer Society Early Detection Professorship [SIOP-06-258-01-COUN]
- Intramural Research Program of the National Cancer Institute, National Institutes of Health
- National Cancer Institute, National Institutes of Health [UM1 CA164920]
- Lithuania (BFBOCC-LT): Research Council of Lithuania [LIG-07/2012]
- LSC [10.0010.08]
- European Social Fund [2009/0220/1DP/1.1.1.2.0/09/APIA/VIAA/016]
- Liepaja City Council, Liepaja, Latvia
- Breast Cancer Research Foundation
- Cancer Association of South Africa (CANSA)
- Morris and Horowitz Families Professorship in Cancer Etiology and Outcomes Research
- NEYE Foundation
- Spanish Association against Cancer (Asociacion Espanola Contra el Cancer) [AECC08]
- Thematic Network Cooperative Research in Cancer (Red Tematica Investigacion Cooperativa en Cancer (RTICC), Centro de Investigacion Cancer, Salamanca, Spain) [RTICC 06/0020/1060]
- Spanish Ministry of Science and Innovation [FIS PI08 1120]
- Fondo de Investigacion Sanitaria (FIS) [SAF2010-20493]
- Fundacion Mutua Madrilena (FMMA)
- City of Hope Clinical Cancer Genetics Community Network and the Hereditary Cancer Research Registry (COH-CCGCRN)
- National Cancer Institute and the Office of the Director, National Institutes of Health [RC4CA153828]
- Italian citizens
- Fondazione IRCCS Istituto Nazionale Tumori
- Italian Association for Cancer Research (AIRC)
- European Union (European Social Fund (ESF)
- Greek national funds through the Education and Lifelong Learning operational program of the National Strategic Reference Framework (NSRF) - Research Funding Program of the General Secretariat for Research and Technology: ARISTEIA
- Heracleitus II: Investing in knowledge society through the European Social Fund
- Deutsches Krebsforschungszentrum (DKFZ)
- National Institute for Health Research (NIHR) grant to the Biomedical Research Centre, Manchester, UK
- NIHR grant to the Biomedical Research Centre at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, London
- University of Kansas Cancer Center [P30 CA168524]
- Kansas Bioscience Authority Eminent Scholar Program
- Chancellors Distinguished Chair in Biomedical Sciences Professorship
- German Cancer Aid [109076]
- Center for Molecular Medicine Cologne (CMMC)
- Ligue National Contre le Cancer
- Association Le cancer du sein, parlons-en! Award
- Canadian Institutes of Health Research for the CIHR Team in Familial Risks of Breast Cancer program
- GOA [BOF10/GOA/019]
- Ghent University Hospital
- National Cancer Institute grants to the GOG Administrative Office and Tissue Bank [CA 27469]
- GOG Statistical and Data Center [CA 37517]
- GOG's Cancer Prevention and Control Committee [CA 101165]
- Instituto de Salud Carlos III (ISCIII), Madrid, Spain [RD12/00369/0006, 12/00539]
- European Regional Development Fund (Fonds europeen de developpement regional (FEDER)) funds
- Helsinki University Central Hospital Research Fund
- Academy of Finland [266528]
- Finnish Cancer Society
- Sigrid Juselius Foundation
- Dutch Cancer Society [NKI1998-1854, NKI2004-3088, NKI2007-3756]
- Netherlands Organization of Scientific Research [NWO 91109024]
- Pink Ribbon grant [110005]
- Biobanking and Molecular Resource Infrastructure (BBMRI) [NWO 184.021.007/CP46]
- Hungarian Research and Technological Innovation Fund (KTIA)/Hungarian Scientific Research Fund (Orszagos Tudomanyos Kutatasi Alapprogramok (OTKA)) [KTIA-OTKA CK-80745, KTIA-OTKA K-112228]
- Institut Catala d'Oncologia (ICO): contract grant sponsor: Asociacion Espanola Contra el Cancer
- Spanish Health Research Foundation
- Ramon Areces Foundation
- Instituto de Salud Carlos III (ISCIII)
- Catalan Health Institute
- Autonomous Government of Catalonia
- International Hereditary Cancer Center (Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland) [PBZ_KBN_122/P05/2004]
- Icelandic Association Walking for Breast Cancer Research
- Landspitali University Hospital Research Fund
- Canadian Institutes of Health Research (CIHR) for the CIHR Team in Familial Risks of Breast Cancer program, Canadian Breast Cancer Research Alliance [019511]
- Ministry of Economic Development, Innovation and Export Trade [PSR-SIIRI-701]
- Ministero della Salute and a 5 x 1,000 Istituto Oncologico Veneto grant
- Liga Portuguesa Contra o Cancro
- National Breast Cancer Foundation
- Queensland Cancer Fund
- Cancer Councils of New South Wales, Victoria, Tasmania and South Australia
- Cancer Foundation of Western Australia
- National Institutes of Health (NIH) through the National Cancer Institute (NCI) [CA 116167, CA 128978, CA 176785]
- NCI Specialized Program of Research Excellence (SPORE) in Breast Cancer [CA116201]
- US Department of Defense Ovarian Cancer Idea award [W81XWH-10-1-0341]
- Ministry of Health of the Czech Republic to Masaryk Memorial Cancer Institute [MMCI 00209805]
- European Regional Development Fund
- State Budget of the Czech Republic (RECAMO) [CZ. 1.05/2.1.00/03.0101]
- Charles University in Prague project [UNCE204024]
- Robert and Kate Niehaus Clinical Cancer Genetics Initiative
- Intramural Research Program of the National Cancer Institute
- Westat, Inc, Rockville, MD, USA [N02-CP-11019-50, N02-CP-65504]
- Clalit Health Services in Israel
- Israel Cancer Association
- Breast Cancer Research Foundation (BCRF), New York, NY, USA
- Russian Federation for Basic Research [11-04-00227, 12-04-00928, 12-04-01490]
- Federal Agency for Science and Innovations, Russia [02.740.11.0780]
- Ohio State University Comprehensive Cancer Center
- Istituto Toscano Tumori (ITT)
- Israeli Inherited Breast Cancer Consortium
- Swedish Breast Cancer
- Swedish Cancer Society
- Ralph and Marion Falk Medical Research Trust
- Entertainment Industry Fund National Women's Cancer Research Alliance
- University of California, Los Angeles Jonsson Comprehensive Cancer Center Foundation: Breast Cancer Research Foundation
- University of California, San Francisco Cancer Risk Program and Helen Diller Family Comprehensive Cancer Center
- Cancer Research UK
- University of Pennsylvania: National Institutes of Health (NIH) [R01 CA102776, R01 CA083855]
- Susan G Komen for the Cure, Basser Center for BRCA
- Victorian Familial Cancer Trials Group (VFCTG): Victorian Cancer Agency, Cancer Australia, National Breast Cancer Foundation
- [5U01 CA113916]
- [R01 CA140323]
- [ISCIIIRETIC RD06/0020/1051]
- [PI09/02483]
- [PI10/01422]
- [PI10/00748]
- [PI13/00285]
- [PI13/00189 2009SGR290]
- [PI13/00189 2009SGR283]
- [CA125183]
- [R01 CA142996]
- [1U01CA161032]
- Cancer Research UK [15007, 11174, 17528, 16563] Funding Source: researchfish
- National Breast Cancer Foundation [IF-12-06] Funding Source: researchfish
- National Institute for Health Research [NF-SI-0510-10096] Funding Source: researchfish
Ask authors/readers for more resources
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.
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