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; H Dean Hosgood; Matthew R Bonner; Neil E Caporaso; Demetrius Albanes; Qing Lan; Nathaniel Rothman

doi:10.1158/1055-9965.EPI-14-0753

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, H Dean Hosgood, Matthew R Bonner, Neil E Caporaso, Demetrius Albanes, Qing Lan, Nathaniel Rothman

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

BACKGROUND: Mitochondrial DNA copy number (mtDNA CN) may be modified by mitochondria in response to oxidative stress. Previously, mtDNA CN was associated with non-Hodgkin lymphoma (NHL) risk, particularly chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). We conducted a replication study in the Prostate, Lung, Colorectal, and Ovarian (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 language	English
Pages (from-to)	148-53
Number of pages	6
Journal	Cancer Epidemiology Biomarkers & Prevention
Volume	24
Issue number	1
DOIs	https://doi.org/10.1158/1055-9965.EPI-14-0753
Publication status	Published - Jan 2015

Keywords

Aged
Chronic Disease
DNA Copy Number Variations
DNA, Mitochondrial
Female
Humans
Leukemia, Lymphocytic, Chronic, B-Cell
Male
Middle Aged
Prospective Studies
Risk Factors

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10.1158/1055-9965.EPI-14-0753

MitochondrialFinal published version, 234 KBLicence: Taverne

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Kim, C., Bassig, B. A., Seow, W. J., Hu, W., Purdue, M. P., Huang, W.-Y., Liu, C.-S., Cheng, W.-L., Männistö, S., Vermeulen, R., Weinstein, S. J., Lim, U., Hosgood, H. D., Bonner, M. R., Caporaso, N. E., 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 & Prevention, 24(1), 148-53. https://doi.org/10.1158/1055-9965.EPI-14-0753

@article{2a1bfa24cdef4328b0711ee31cf0046b,

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

abstract = "BACKGROUND: Mitochondrial DNA copy number (mtDNA CN) may be modified by mitochondria in response to oxidative stress. Previously, mtDNA CN was associated with non-Hodgkin lymphoma (NHL) risk, particularly chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). We conducted a replication study in the Prostate, Lung, Colorectal, and Ovarian (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.",

keywords = "Aged, Chronic Disease, DNA Copy Number Variations, DNA, Mitochondrial, Female, Humans, Leukemia, Lymphocytic, Chronic, B-Cell, Male, Middle Aged, Prospective Studies, Risk Factors",

author = "Christopher Kim and Bassig, {Bryan A} and Seow, {Wei Jie} and Wei Hu and Purdue, {Mark P} and Wen-Yi Huang and Chin-San Liu and Wen-Ling Cheng and Satu M{\"a}nnist{\"o} and Roel Vermeulen and Weinstein, {Stephanie J} and Unhee Lim and Hosgood, {H Dean} and Bonner, {Matthew R} and Caporaso, {Neil E} and Demetrius Albanes and Qing Lan and Nathaniel Rothman",

year = "2015",

month = jan,

doi = "10.1158/1055-9965.EPI-14-0753",

language = "English",

volume = "24",

pages = "148--53",

journal = "Cancer Epidemiology Biomarkers & Prevention",

issn = "1055-9965",

publisher = "American Association for Cancer Research Inc.",

number = "1",

}

Kim, C, Bassig, BA, Seow, WJ, Hu, W, Purdue, MP, Huang, W-Y, Liu, C-S, Cheng, W-L, 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 & Prevention, vol. 24, no. 1, pp. 148-53. https://doi.org/10.1158/1055-9965.EPI-14-0753

TY - JOUR

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, H Dean

AU - Bonner, Matthew R

AU - Caporaso, Neil E

AU - Albanes, Demetrius

AU - Lan, Qing

AU - Rothman, Nathaniel

PY - 2015/1

Y1 - 2015/1

N2 - BACKGROUND: Mitochondrial DNA copy number (mtDNA CN) may be modified by mitochondria in response to oxidative stress. Previously, mtDNA CN was associated with non-Hodgkin lymphoma (NHL) risk, particularly chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). We conducted a replication study in the Prostate, Lung, Colorectal, and Ovarian (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, mtDNA CN was associated with non-Hodgkin lymphoma (NHL) risk, particularly chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). We conducted a replication study in the Prostate, Lung, Colorectal, and Ovarian (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.

KW - Aged

KW - Chronic Disease

KW - DNA Copy Number Variations

KW - DNA, Mitochondrial

KW - Female

KW - Humans

KW - Leukemia, Lymphocytic, Chronic, B-Cell

KW - Male

KW - Middle Aged

KW - Prospective Studies

KW - Risk Factors

U2 - 10.1158/1055-9965.EPI-14-0753

DO - 10.1158/1055-9965.EPI-14-0753

M3 - Article

C2 - 25293880

SN - 1055-9965

VL - 24

SP - 148

EP - 153

JO - Cancer Epidemiology Biomarkers & Prevention

JF - Cancer Epidemiology Biomarkers & Prevention

IS - 1

ER -

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

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