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

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 leu...

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Main Authors: Hosnijeh, F, Lan, Q, Rothman, N, San Liu, C, Cheng, W, Nieters, A, Guldberg, P, Tjønneland, A, Campa, D, Martino, A, Boeing, H, Trichopoulou, A, Lagiou, P, Trichopoulos, D, Krogh, V, Tumino, R, Panico, S, Masala, G, Weiderpass, E, Huerta Castaño, J, Ardanaz, E, Sala, N, Dorronsoro, M, Quirós, JR, Sánchez, M
Format: Journal article
Language:English
Published: 2014
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author Hosnijeh, F
Lan, Q
Rothman, N
San Liu, C
Cheng, W
Nieters, A
Guldberg, P
Tjønneland, A
Campa, D
Martino, A
Boeing, H
Trichopoulou, A
Lagiou, P
Trichopoulos, D
Krogh, V
Tumino, R
Panico, S
Masala, G
Weiderpass, E
Huerta Castaño, J
Ardanaz, E
Sala, N
Dorronsoro, M
Quirós, JR
Sánchez, M
author_facet Hosnijeh, F
Lan, Q
Rothman, N
San Liu, C
Cheng, W
Nieters, A
Guldberg, P
Tjønneland, A
Campa, D
Martino, A
Boeing, H
Trichopoulou, A
Lagiou, P
Trichopoulos, D
Krogh, V
Tumino, R
Panico, S
Masala, G
Weiderpass, E
Huerta Castaño, J
Ardanaz, E
Sala, N
Dorronsoro, M
Quirós, JR
Sánchez, M
author_sort Hosnijeh, F
collection OXFORD
description 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.
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spelling oxford-uuid:5f6c1fae-4f68-4dfb-b787-c0ac6ade75ed2022-03-26T17:46:56ZMitochondrial DNA copy number and future risk of B-cell lymphoma in a nested case-control study in the prospective EPIC cohort.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:5f6c1fae-4f68-4dfb-b787-c0ac6ade75edEnglishSymplectic Elements at Oxford2014Hosnijeh, FLan, QRothman, NSan Liu, CCheng, WNieters, AGuldberg, PTjønneland, ACampa, DMartino, ABoeing, HTrichopoulou, ALagiou, PTrichopoulos, DKrogh, VTumino, RPanico, SMasala, GWeiderpass, EHuerta Castaño, JArdanaz, ESala, NDorronsoro, MQuirós, JRSánchez, MIt 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.
spellingShingle Hosnijeh, F
Lan, Q
Rothman, N
San Liu, C
Cheng, W
Nieters, A
Guldberg, P
Tjønneland, A
Campa, D
Martino, A
Boeing, H
Trichopoulou, A
Lagiou, P
Trichopoulos, D
Krogh, V
Tumino, R
Panico, S
Masala, G
Weiderpass, E
Huerta Castaño, J
Ardanaz, E
Sala, N
Dorronsoro, M
Quirós, JR
Sánchez, M
Mitochondrial DNA copy number and future risk of B-cell lymphoma in a nested case-control study in the prospective EPIC cohort.
title Mitochondrial DNA copy number and future risk of B-cell lymphoma in a nested case-control study in the prospective EPIC cohort.
title_full Mitochondrial DNA copy number and future risk of B-cell lymphoma in a nested case-control study in the prospective EPIC cohort.
title_fullStr Mitochondrial DNA copy number and future risk of B-cell lymphoma in a nested case-control study in the prospective EPIC cohort.
title_full_unstemmed Mitochondrial DNA copy number and future risk of B-cell lymphoma in a nested case-control study in the prospective EPIC cohort.
title_short Mitochondrial DNA copy number and future risk of B-cell lymphoma in a nested case-control study in the prospective EPIC cohort.
title_sort mitochondrial dna copy number and future risk of b cell lymphoma in a nested case control study in the prospective epic cohort
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