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

Fatemeh Saberi Hosnijeh, Qing Lan, Nathaniel Rothman, Chin San Liu, Wen Ling Cheng, Alexandra Nieters, Per Guldberg, Anne Tjønneland, Daniele Campa, Alessandro Martino, Heiner Boeing, Antonia Trichopoulou, Pagona Lagiou, Dimitrios Trichopoulos, Vittorio Krogh, Rosario Tumino, Salvatore Panico, Giovanna Masala, Elisabete Weiderpass, José María Huerta CastanõEva Ardanaz, Núria Sala, Miren Dorronsoro, J. Ramón Quirós, Mariá José Sánchez, Beatrice Melin, Ann Sofie Johansson, Johan Malm, Signe Borgquist, Petra H. Peeters, H. Bas Bueno-De-Mesquita, Nick Wareham, Kay Tee Khaw, Ruth C. Travis, Paul Brennan, Afshan Siddiq, Elio Riboli, Paolo Vineis, Roel Vermeulen

Research output: Contribution to journalArticlepeer-review

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. Usinganested case-controlstudy, 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; Ptrend = .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.

Original languageEnglish
Pages (from-to)530-535
Number of pages6
JournalBlood
Volume124
Issue number4
DOIs
Publication statusPublished - Jul 24 2014

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

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