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Mitochondrial DNA copy number variation, leukocyte telomere length, and breast cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) study

Campa D 1 , Barrdahl M 2 , Santoro A 3 , Severi G 4 , Baglietto L 4 , Omichessan H 4 Show all authors , Tumino R 5 , Bueno-de-Mesquita HBA 6 , Peeters PH 7 , Weiderpass E 8 , Chirlaque MD 9 , Rodríguez-Barranco M 10 , Agudo A 11 , Gunter M 12 , Dossus L 12 , Krogh V 13 , Matullo G 14 , Trichopoulou A 15 , Travis RC 16 , Canzian F 17 , Kaaks R 18

Affiliations 

  • 1 Department of Biology, University of Pisa, Pisa, Italy
  • 2 Division of Cancer Epidemiology, German Cancer Research Center/Deutsches Krebsforschungszentrum (DKFZ), Im Neuenheimer Feld 280, 69120, Heidelberg, Germany
  • 3 Department of Experimental, Diagnostic and Specialty Medicine (DIMES), University of Bologna, Bologna, Italy
  • 4 Centre de Recherche en épidémiologie et Santé des populations (CESP), Faculté de médecine - Université Paris-Sud, Faculté de médecine - Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Institut national de la santé et de la recherche médicale (INSERM), Université Paris-Saclay, 94805, Villejuif, France
  • 5 Cancer Registry and Histopathology Department, "Civic - M.P. Arezzo" Hospital, Azienda Sanitaria Provinciale Di Ragusa, Ragusa, Italy
  • 6 Department for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment (RIVM), PO Box 1, 3720 BA, Bilthoven, The Netherlands
  • 7 Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands
  • 8 Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, The Arctic University of Norway, Tromsø, Norway
  • 9 Department of Epidemiology, Regional Health Council, Biomedical Research Institute of Murcia (IMIB-Arrixaca), Murcia, Spain
  • 10 Consorcio de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain
  • 11 Unit of Nutrition and Cancer, Bellvitge Biomedical Research Institute (IDIBELL), Catalan Institute of Oncology, L'Hospitalet de Llobregat, 08908, Barcelona, Spain
  • 12 International Agency for Research on Cancer, Lyon, France
  • 13 Epidemiology and Prevention Unit, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS)-Istituto Nazionale dei Tumori, Via Venezian, 120133, Milan, Italy
  • 14 Department Medical Sciences, University of Torino and Human Genetics Foundation (HuGeF), Torino, Italy
  • 15 Hellenic Health Foundation, 11527, Athens, Greece
  • 16 Cancer Epidemiology Unit, Nuffield Department of Population Health University of Oxford, Oxford, OX3 0NR, UK
  • 17 Genomic Epidemiology Group, German Cancer Research Center/Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Germany
  • 18 Division of Cancer Epidemiology, German Cancer Research Center/Deutsches Krebsforschungszentrum (DKFZ), Im Neuenheimer Feld 280, 69120, Heidelberg, Germany. r.kaaks@dkfz.de
Breast Cancer Res, 2018 04 17;20(1):29.
PMID: 29665866 DOI: 10.1186/s13058-018-0955-5

Abstract

BACKGROUND: Leukocyte telomere length (LTL) and mitochondrial genome (mtDNA) copy number and deletions have been proposed as risk markers for various cancer types, including breast cancer (BC).

METHODS: To gain a more comprehensive picture on how these markers can modulate BC risk, alone or in conjunction, we performed simultaneous measurements of LTL and mtDNA copy number in up to 570 BC cases and 538 controls from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. As a first step, we measured LTL and mtDNA copy number in 96 individuals for which a blood sample had been collected twice with an interval of 15 years.

RESULTS: According to the intraclass correlation (ICC), we found very good stability over the time period for both measurements, with ICCs of 0.63 for LTL and 0.60 for mtDNA copy number. In the analysis of the entire study sample, we observed that longer LTL was strongly associated with increased risk of BC (OR 2.71, 95% CI 1.58-4.65, p = 3.07 × 10- 4 for highest vs. lowest quartile; OR 3.20, 95% CI 1.57-6.55, p = 1.41 × 10- 3 as a continuous variable). We did not find any association between mtDNA copy number and BC risk; however, when considering only the functional copies, we observed an increased risk of developing estrogen receptor-positive BC (OR 2.47, 95% CI 1.05-5.80, p = 0.04 for highest vs. lowest quartile).

CONCLUSIONS: We observed a very good correlation between the markers over a period of 15 years. We confirm a role of LTL in BC carcinogenesis and suggest an effect of mtDNA copy number on BC risk.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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