Mitochondrial DNA copy number and chronic lymphocytic leukemia/small lymphocytic lymphoma risk in two prospective studies

Christopher Kim, Bryan A. Bassig, Wei Jie Seow, Wei Hu, Mark P. Purdue, Wen Yi Huang, Chin San Liu, Wen Ling Cheng, Satu Männistö, Roel Vermeulen, Stephanie J. Weinstein, Unhee Lim, Howard D. Hosgood, Matthew R. Bonner, Neil E. Caporaso, Demetrius Albanes, Qing Lan, Nathaniel Rothman

Research output: Contribution to journalArticle

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Abstract

Background: Mitochondrial DNA copy number (mtDNA CN) may be modified by mitochondria in response to oxidative stress. Previously, mtDNACNwas associatedwithnon-Hodgkin lymphoma (NHL) risk, particularly chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL).We conducted a replication study in the Prostate, Lung, Colorectal, andOvarian (PLCO) study and pooled with published ATBC (Alpha-Tocopherol, Beta-Carotene) data. Methods: In PLCO, 292 NHL cases (95 CLL/SLL cases) and 301 controls were pooled with 142 NHL cases (47 CLL/SLL cases) and 142 controls from ATBC. Subjects answered a questionnaire and provided blood. DNA was extracted from prediagnostic peripheral white blood, and mtDNA CN assayed by quantitative polymerase chain reaction. Unconditional logistic regression estimated mtDNA CN and NHL risk by odds ratios (OR) and 95% confidence intervals (95% CI). Results: Greater mtDNA CN was associated with increased risk of CLL/SLL among males in PLCO (3rd vs. 1st tertile: OR, 2.21; 95% CI, 1.03-4.72; Ptrend: 0.049) and pooled (T3 vs. T1: OR, 3.12; 95% CI, 1.72-5.68; Ptrend: 0.0002). Association was stronger among male smokers (Ptrend: <0.0001) and essentially identical for cases diagnosed <6, >6-8, and >8 years from blood draw (pooled: Pinteraction: 0.65). mtDNA CN and risk of other NHL subtypes and multiple myeloma showed no association. Conclusions and Impact: Mitochondrial DNA CN was associated with risk of CLL/SLL in males/male smokers. The risk was observed among cases diagnosed as long as 8 years after blood draw. These results suggest that higher mtDNA CN may reflect a process involved in CLL/SLL development.

Original languageEnglish (US)
Pages (from-to)148-153
Number of pages6
JournalCancer Epidemiology Biomarkers and Prevention
Volume24
Issue number1
DOIs
StatePublished - Jan 1 2015

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B-Cell Chronic Lymphocytic Leukemia
Mitochondrial DNA
Prospective Studies
Odds Ratio
Prostate
beta Carotene
alpha-Tocopherol
Confidence Intervals
Lung
Multiple Myeloma
Hodgkin Disease
Mitochondria
Oxidative Stress
Logistic Models

ASJC Scopus subject areas

  • Epidemiology
  • Oncology

Cite this

Mitochondrial DNA copy number and chronic lymphocytic leukemia/small lymphocytic lymphoma risk in two prospective studies. / Kim, Christopher; Bassig, Bryan A.; Seow, Wei Jie; Hu, Wei; Purdue, Mark P.; Huang, Wen Yi; Liu, Chin San; Cheng, Wen Ling; Männistö, Satu; Vermeulen, Roel; Weinstein, Stephanie J.; Lim, Unhee; Hosgood, Howard D.; Bonner, Matthew R.; Caporaso, Neil E.; Albanes, Demetrius; Lan, Qing; Rothman, Nathaniel.

In: Cancer Epidemiology Biomarkers and Prevention, Vol. 24, No. 1, 01.01.2015, p. 148-153.

Research output: Contribution to journalArticle

Kim, C, Bassig, BA, Seow, WJ, Hu, W, Purdue, MP, Huang, WY, Liu, CS, Cheng, WL, Männistö, S, Vermeulen, R, Weinstein, SJ, Lim, U, Hosgood, HD, Bonner, MR, Caporaso, NE, Albanes, D, Lan, Q & Rothman, N 2015, 'Mitochondrial DNA copy number and chronic lymphocytic leukemia/small lymphocytic lymphoma risk in two prospective studies', Cancer Epidemiology Biomarkers and Prevention, vol. 24, no. 1, pp. 148-153. https://doi.org/10.1158/1055-9965.EPI-14-0753
Kim, Christopher ; Bassig, Bryan A. ; Seow, Wei Jie ; Hu, Wei ; Purdue, Mark P. ; Huang, Wen Yi ; Liu, Chin San ; Cheng, Wen Ling ; Männistö, Satu ; Vermeulen, Roel ; Weinstein, Stephanie J. ; Lim, Unhee ; Hosgood, Howard D. ; Bonner, Matthew R. ; Caporaso, Neil E. ; Albanes, Demetrius ; Lan, Qing ; Rothman, Nathaniel. / Mitochondrial DNA copy number and chronic lymphocytic leukemia/small lymphocytic lymphoma risk in two prospective studies. In: Cancer Epidemiology Biomarkers and Prevention. 2015 ; Vol. 24, No. 1. pp. 148-153.
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abstract = "Background: Mitochondrial DNA copy number (mtDNA CN) may be modified by mitochondria in response to oxidative stress. Previously, mtDNACNwas associatedwithnon-Hodgkin lymphoma (NHL) risk, particularly chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL).We conducted a replication study in the Prostate, Lung, Colorectal, andOvarian (PLCO) study and pooled with published ATBC (Alpha-Tocopherol, Beta-Carotene) data. Methods: In PLCO, 292 NHL cases (95 CLL/SLL cases) and 301 controls were pooled with 142 NHL cases (47 CLL/SLL cases) and 142 controls from ATBC. Subjects answered a questionnaire and provided blood. DNA was extracted from prediagnostic peripheral white blood, and mtDNA CN assayed by quantitative polymerase chain reaction. Unconditional logistic regression estimated mtDNA CN and NHL risk by odds ratios (OR) and 95{\%} confidence intervals (95{\%} CI). Results: Greater mtDNA CN was associated with increased risk of CLL/SLL among males in PLCO (3rd vs. 1st tertile: OR, 2.21; 95{\%} CI, 1.03-4.72; Ptrend: 0.049) and pooled (T3 vs. T1: OR, 3.12; 95{\%} CI, 1.72-5.68; Ptrend: 0.0002). Association was stronger among male smokers (Ptrend: <0.0001) and essentially identical for cases diagnosed <6, >6-8, and >8 years from blood draw (pooled: Pinteraction: 0.65). mtDNA CN and risk of other NHL subtypes and multiple myeloma showed no association. Conclusions and Impact: Mitochondrial DNA CN was associated with risk of CLL/SLL in males/male smokers. The risk was observed among cases diagnosed as long as 8 years after blood draw. These results suggest that higher mtDNA CN may reflect a process involved in CLL/SLL development.",
author = "Christopher Kim and Bassig, {Bryan A.} and Seow, {Wei Jie} and Wei Hu and Purdue, {Mark P.} and Huang, {Wen Yi} and Liu, {Chin San} and Cheng, {Wen Ling} and Satu M{\"a}nnist{\"o} and Roel Vermeulen and Weinstein, {Stephanie J.} and Unhee Lim and Hosgood, {Howard D.} and Bonner, {Matthew R.} and Caporaso, {Neil E.} and Demetrius Albanes and Qing Lan and Nathaniel Rothman",
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T1 - Mitochondrial DNA copy number and chronic lymphocytic leukemia/small lymphocytic lymphoma risk in two prospective studies

AU - Kim, Christopher

AU - Bassig, Bryan A.

AU - Seow, Wei Jie

AU - Hu, Wei

AU - Purdue, Mark P.

AU - Huang, Wen Yi

AU - Liu, Chin San

AU - Cheng, Wen Ling

AU - Männistö, Satu

AU - Vermeulen, Roel

AU - Weinstein, Stephanie J.

AU - Lim, Unhee

AU - Hosgood, Howard D.

AU - Bonner, Matthew R.

AU - Caporaso, Neil E.

AU - Albanes, Demetrius

AU - Lan, Qing

AU - Rothman, Nathaniel

PY - 2015/1/1

Y1 - 2015/1/1

N2 - Background: Mitochondrial DNA copy number (mtDNA CN) may be modified by mitochondria in response to oxidative stress. Previously, mtDNACNwas associatedwithnon-Hodgkin lymphoma (NHL) risk, particularly chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL).We conducted a replication study in the Prostate, Lung, Colorectal, andOvarian (PLCO) study and pooled with published ATBC (Alpha-Tocopherol, Beta-Carotene) data. Methods: In PLCO, 292 NHL cases (95 CLL/SLL cases) and 301 controls were pooled with 142 NHL cases (47 CLL/SLL cases) and 142 controls from ATBC. Subjects answered a questionnaire and provided blood. DNA was extracted from prediagnostic peripheral white blood, and mtDNA CN assayed by quantitative polymerase chain reaction. Unconditional logistic regression estimated mtDNA CN and NHL risk by odds ratios (OR) and 95% confidence intervals (95% CI). Results: Greater mtDNA CN was associated with increased risk of CLL/SLL among males in PLCO (3rd vs. 1st tertile: OR, 2.21; 95% CI, 1.03-4.72; Ptrend: 0.049) and pooled (T3 vs. T1: OR, 3.12; 95% CI, 1.72-5.68; Ptrend: 0.0002). Association was stronger among male smokers (Ptrend: <0.0001) and essentially identical for cases diagnosed <6, >6-8, and >8 years from blood draw (pooled: Pinteraction: 0.65). mtDNA CN and risk of other NHL subtypes and multiple myeloma showed no association. Conclusions and Impact: Mitochondrial DNA CN was associated with risk of CLL/SLL in males/male smokers. The risk was observed among cases diagnosed as long as 8 years after blood draw. These results suggest that higher mtDNA CN may reflect a process involved in CLL/SLL development.

AB - Background: Mitochondrial DNA copy number (mtDNA CN) may be modified by mitochondria in response to oxidative stress. Previously, mtDNACNwas associatedwithnon-Hodgkin lymphoma (NHL) risk, particularly chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL).We conducted a replication study in the Prostate, Lung, Colorectal, andOvarian (PLCO) study and pooled with published ATBC (Alpha-Tocopherol, Beta-Carotene) data. Methods: In PLCO, 292 NHL cases (95 CLL/SLL cases) and 301 controls were pooled with 142 NHL cases (47 CLL/SLL cases) and 142 controls from ATBC. Subjects answered a questionnaire and provided blood. DNA was extracted from prediagnostic peripheral white blood, and mtDNA CN assayed by quantitative polymerase chain reaction. Unconditional logistic regression estimated mtDNA CN and NHL risk by odds ratios (OR) and 95% confidence intervals (95% CI). Results: Greater mtDNA CN was associated with increased risk of CLL/SLL among males in PLCO (3rd vs. 1st tertile: OR, 2.21; 95% CI, 1.03-4.72; Ptrend: 0.049) and pooled (T3 vs. T1: OR, 3.12; 95% CI, 1.72-5.68; Ptrend: 0.0002). Association was stronger among male smokers (Ptrend: <0.0001) and essentially identical for cases diagnosed <6, >6-8, and >8 years from blood draw (pooled: Pinteraction: 0.65). mtDNA CN and risk of other NHL subtypes and multiple myeloma showed no association. Conclusions and Impact: Mitochondrial DNA CN was associated with risk of CLL/SLL in males/male smokers. The risk was observed among cases diagnosed as long as 8 years after blood draw. These results suggest that higher mtDNA CN may reflect a process involved in CLL/SLL development.

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