A prospective study of mitochondrial DNA copy number and risk of non-Hodgkin lymphoma

Mitochondrial DNA (mtDNA) copy number is increased in patients with chronic lymphocytic leukemia (CLL), in Burkitt lymphoma and Epstein-Barr virus-transformed lymphoblastoid cell lines, and in T cells activated via the T-cell receptor. We hypothesized that having a higher mtDNA copy number in peripheral white blood cell DNA from healthy subjects would be associated with future risk of non-Hodgkin lymphoma (NHL). We analyzed mtDNA copy number in 104 incident male NHL cases and 104 matched controls within the prospective Alpha-Tocopherol, Beta-Carotene (ATBC) Cancer Prevention cohort. There was a dose-response relationship between tertiles of mtDNA copy number and risk of NHL (odds ratio OR, 95% confidence interval CI: 1.0; 1.4 0.7-2.8; and 2.4 1.0-5.5, respectively; P(trend) = .046). The effect was most pronounced for the CLL/small lymphocytic lymphoma (SLL) subtype (OR: 1.0; 3.2 0.7-15.7; 14.1 1.9-103.2; P(trend) = .009). These results suggest that mtDNA copy number could be associated with the risk of NHL, particularly CLL/SLL.