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
N1 - Publisher Copyright:
© 2014 American Association for Cancer Research.
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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U2 - 10.1158/1055-9965.EPI-14-0753
DO - 10.1158/1055-9965.EPI-14-0753
M3 - Article
C2 - 25293880
AN - SCOPUS:84921020197
SN - 1055-9965
VL - 24
SP - 148
EP - 153
JO - Cancer Epidemiology Biomarkers and Prevention
JF - Cancer Epidemiology Biomarkers and Prevention
IS - 1
ER -