Skip to Main Content

An official website of the United States government

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

About this Publication
Title
Mitochondrial DNA copy number and chronic lymphocytic leukemia/small lymphocytic lymphoma risk in two prospective studies.
Pubmed ID
25293880 (View this publication on the PubMed website)
Digital Object Identifier
Publication
Cancer Epidemiol Biomarkers Prev. 2015 Jan; Volume 24 (Issue 1): Pages 148-53
Authors
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
Affiliations
  • Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland. christopher.kim@nih.gov.
  • Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
  • Neurology and Vascular and Genomic Center, Changhua Christian Hospital, Changhua, Taiwan.
  • Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland.
  • Institute for Risk Assessment Sciences, Utrecht University, Utrecht, the Netherlands.
  • Epidemiology Program, University of Hawaii Cancer Center, Honolulu, Hawaii.
  • Albert Einstein College of Medicine, Yeshiva University, Bronx, New York.
  • Department of Epidemiology and Environmental Health, State University of New York at Buffalo, Buffalo, New York.
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.

Related CDAS Studies
Related CDAS Projects