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Blood. 2014 Jul 24;124(4):530-5. doi: 10.1182/blood-2013-10-532085. Epub 2014 Jun 4.

Mitochondrial DNA copy number and future risk of B-cell lymphoma in a nested case-control study in the prospective EPIC cohort.

Author information

1
Institute for Risk Assessment Sciences, Division Environmental Epidemiology, Utrecht University, Utrecht, The Netherlands; Zanjan University of Medical Sciences, Zanjan, Iran;
2
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD;
3
Department of Neurology and Vascular and Genomic Center, Changhua Christian Hospital, Changhua, Taiwan; Graduate Institute of Integrated Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan;
4
Laboratory of Mitochondrial Medicine, Chunghua Christian Hospital, Taipei, Taiwan;
5
Centre of Chronic Immunodeficiency, University Medical Centre Freiburg, Freiburg, Germany;
6
Danish Cancer Society Research Center, Copenhagen, Denmark;
7
Genomic Epidemiology Group, German Cancer Research Center, Heidelberg, Germany;
8
Department of Epidemiology, German Institute of Human Nutrition, Potsdam-Rehbrücke, Nuthetal, Germany;
9
Hellenic Health Foundation, Athens, Greece; WHO Collaborating Center for Food and Nutrition Policies, Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, Athens, Greece;
10
WHO Collaborating Center for Food and Nutrition Policies, Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, Athens, Greece; Department of Epidemiology, Harvard School of Public Health, Boston, MA; Bureau of Epidemiologic Research, Academy of Athens, Athens, Greece;
11
Hellenic Health Foundation, Athens, Greece; Department of Epidemiology, Harvard School of Public Health, Boston, MA; Bureau of Epidemiologic Research, Academy of Athens, Athens, Greece;
12
Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy;
13
Cancer Registry and Histopathology Unit, "Civic - M.P. Arezzo" Hospital, ASP Ragusa, Italy;
14
Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy;
15
Molecular and Nutritional Epidemiology Unit, ISPO Cancer Research and Prevention Institute, Florence, Italy;
16
Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, Tromsø, Norway; Department of Research, Cancer Registry of Norway, Oslo, Norway; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Samfundet Folkhälsan, Helsinki, Finland;
17
Department of Epidemiology, Murcia Regional Health Council, Murcia, Spain; CIBER Epidemiology and Public Health CIBERESP, Spain;
18
CIBER Epidemiology and Public Health CIBERESP, Spain; Navarre Public Health Institute, Pamplona, Spain;
19
Translational Research Laboratory and Unit of Nutrition, Environment and Cancer Research Program in Cancer Epidemiology, Catalan Institute of Oncology, Biomedical Research Institute (IDIBELL), Barcelona, Spain;
20
Public Health Direction and Biodonostia Research Institute Ciberesp, Basque Regional Health Department, Vitoria, Spain;
21
Public Health Directorate, Asturias, Spain;
22
CIBER Epidemiology and Public Health CIBERESP, Spain; Andalusian School of Public Health, Granada, Spain; Instituto de Investigación Biosanitario de Granada, Granada, Spain;
23
Department of Radiation Sciences, Oncology Umeå University, Umeå, Sweden;
24
Department of Laboratory Medicine, Clinical Chemistry, Lund University, Malmö, Sweden; Skåne University Hospital, Malmö, Sweden;
25
Division of Oncology, Department of Clinical Sciences, Lund University, Malmö, Sweden;
26
Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht;
27
National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands; Department of Gastroenterology and Hepatology, University Medical Centre, Utrecht, The Netherlands; The School of Public Health, Imperial College London, London, United Kingdom;
28
MRC Epidemiology Unit, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, United Kingdom; School of Clinical Medicine, University of Cambridge, Cambridge, United Kingdom;
29
School of Clinical Medicine, University of Cambridge, Cambridge, United Kingdom;
30
Cancer Epidemiology Unit, University of Oxford, Oxford, United Kingdom;
31
Genetics Section, International Agency for Research on Cancer, Lyon, France;
32
Department of Genomics of Common Disease, School of Public Health, Imperial College London, London, United Kingdom;
33
Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom; and.
34
The School of Public Health, Imperial College London, London, United Kingdom; Human Genetics Foundation, Turin, Italy.
35
Institute for Risk Assessment Sciences, Division Environmental Epidemiology, Utrecht University, Utrecht, The Netherlands; Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht;

Abstract

It has been suggested that mitochondrial dysfunction and DNA damage are involved in lymphomagenesis. Increased copy number of mitochondrial DNA (mtDNA) as a compensatory mechanism of mitochondrial dysfunction previously has been associated with B-cell lymphomas, in particular chronic lymphocytic leukemia (CLL). However, current evidence is limited and based on a relatively small number of cases. Using a nested case-control study, we extended these findings with a focus on subtype-specific analyses. Relative mtDNA copy number was measured in the buffy coat of prospectively collected blood of 469 lymphoma cases and 469 matched controls. The association between mtDNA copy number and the risk of developing lymphoma and histologic subtypes was examined using logistic regression models. We found no overall association between mtDNA and risk of lymphoma. Subtype analyses revealed significant increased risks of CLL (n = 102) with increasing mtDNA copy number (odds ratio = 1.34, 1.44, and 1.80 for quartiles 2-4, respectively; P trend = .001). mtDNA copy number was not associated with follow-up time, suggesting that this observation is not strongly influenced by indolent disease status. This study substantially strengthens the evidence that mtDNA copy number is related to risk of CLL and supports the importance of mitochondrial dysfunction as a possible mechanistic pathway in CLL ontogenesis.

PMID:
24899624
PMCID:
PMC4110659
DOI:
10.1182/blood-2013-10-532085
[Indexed for MEDLINE]
Free PMC Article

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