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

Author

Risk Assessment of Toxic and Immunomodulatory Agents, LS IRAS EEPI GRA (Gezh.risico-analyse), Dep IRAS, IRAS RATIA-SIB, Hosnijeh, Fatemeh Saberi, Lan, Q., Rothman, N., San Liu, C., Cheng, W.L., Nieters, A., Guldberg, P., Tjonneland, A., Campa, D., Martino, A., Boeing, H., Trichopoulou, A., Lagiou, P., Trichopoulous, D., Krogh, V., Tumino, R., Panico, S., Masala, G., Quiros, J.R., Weiderpass, E., Borgquist, S., Peeters, P.H.M., Bueno de Mesquita, H.B., et al, X, Vermeulen, R.C.H., Risk Assessment of Toxic and Immunomodulatory Agents, LS IRAS EEPI GRA (Gezh.risico-analyse), Dep IRAS, IRAS RATIA-SIB, Hosnijeh, Fatemeh Saberi, Lan, Q., Rothman, N., San Liu, C., Cheng, W.L., Nieters, A., Guldberg, P., Tjonneland, A., Campa, D., Martino, A., Boeing, H., Trichopoulou, A., Lagiou, P., Trichopoulous, D., Krogh, V., Tumino, R., Panico, S., Masala, G., Quiros, J.R., Weiderpass, E., Borgquist, S., Peeters, P.H.M., Bueno de Mesquita, H.B., et al, X, and Vermeulen, R.C.H.

Published
2014

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

Author

Hosnijeh FS, Lan Q, Rothman N, San Liu C, Cheng WL, 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 JM, Ardanaz E, Sala N, Dorronsoro M, Quirós JR, Sánchez MJ, Melin B, Johansson AS, Malm J, Borgquist S, Peeters PH, Bueno-de-Mesquita HB, Wareham N, Khaw KT, Travis RC, Brennan P, Siddiq A, Riboli E, Vineis P, and Vermeulen R

Subjects
Adult, Aged, Case-Control Studies, Female, Follow-Up Studies, Humans, Male, Middle Aged, Prognosis, Prospective Studies, Real-Time Polymerase Chain Reaction, Risk Factors, DNA Copy Number Variations genetics, DNA, Mitochondrial genetics, Hodgkin Disease genetics, Lymphoma, B-Cell genetics, Lymphoma, T-Cell genetics, Mitochondria genetics
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.

Published
2014
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