Mitochondrial DNA fraction breaks are associated with an increased likelihood of developing non-Hodgkin lymphoma (NHL), according to research published in JAMA Network Open.

For this study, researchers analyzed data from the 1985-1988 Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study, which included nearly 30,000 men in Finland.

The researchers compared 107 patients with NHL to 107 matched control individuals. Mitochondrial DNA fraction breaks were quantified using high-throughput quantitative PCR assays.

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The baseline characteristics of the NHL and control patients were similar for body mass index, smoking status, and supplementation with alpha tocopherol, beta carotene, both, or placebo.

The median mitochondrial DNA copy number was 0.9075 in the control group and 0.9895 in the NHL patients (P <.001). The median number of mitochondrial DNA fraction breaks was 0.183 in the control group and 0.213 in the NHL patients (P <.001).

Patients with a higher number of mitochondrial DNA fraction breaks than the median (0.2045-0.557) had significantly greater odds of developing NHL (odds ratio, 4.03; 95% CI, 1.74-9.33; P =.001) after adjustment for mitochondrial DNA copy number, smoking pack-years, number of cigarettes per day, and body mass index.

When patients were divided into quartiles according to the number of mitochondrial DNA fraction breaks, a dose-response relationship was observed. Compared to the first quartile (0.116-0.149), the odds ratio for NHL was:

  • 1.72 (95% CI, 0.49-6.06; P =.40) for the second quartile (0.150-0.182)
  • 3.89 (95% CI, 1.29-11.76; P =.02) for the third quartile (0.183-0.234)
  • 8.37 (95% CI, 2.41-29.03; P =.001) for the fourth quartile (0.235-0.557).

“[T]o the best of our knowledge, we are first to report that increased mtDNAfb [mitochondrial DNA fraction breaks] was associated with increased future risk of NHL in a dose-dependent manner, indicating that mtDNAfb may be a useful biomarker for future risk of this hematologic cancer,” the researchers wrote. “Additional studies are needed to replicate our findings, especially in more diverse populations, including women and nonsmokers.”


Hosgood HD (III), Davitt M, Cawthon R, et al. Mitochondrial DNA fragmentation and risk of non-Hodgkin lymphoma. JAMA Netw Open. Published online August 2, 2023. doi:10.1001/jamanetworkopen.2023.26885

This article originally appeared on Cancer Therapy Advisor