Mitochondrial DNA Copy Number and Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma Risk in Two Prospective Studies

作者：Kim Christopher^*; Bassig Bryan A; Seow Wei Jie; Hu Wei; Purdue Mark P; Huang Wen Yi; Liu Chin San; Cheng Wen Ling; Mannisto Satu; Vermeulen Roel; Weinstein Stephanie J; Lim Unhee; Hosgood H Dean; Bonner Matthew R; Caporaso Neil E; Albanes Demetrius; Lan Qing; Rothman Nathaniel

来源：Cancer Epidemiology Biomarkers & Prevention, 2015, 24(1): 148-153.

DOI：10.1158/1055-9965.EPI-14-0753

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; P-trend: 0.049) and pooled (T3 vs. T1: OR, 3.12; 95% CI, 1.72-5.68; P-trend: 0.0002). Association was stronger among male smokers (P-trend: < 0.0001) and essentially identical for cases diagnosed < 6, > 6-8, and > 8 years from blood draw (pooled: P-interaction: 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.

• 出版日期2015-1
• 单位NIH