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. 2022 Jul;11(7):1268-1278.
doi: 10.21037/tlcr-21-979.

Peripheral blood leukocyte mitochondrial DNA content and risk of lung cancer

Gregory T Kennedy  1 , Nandita Mitra  2 , Trevor M Penning  3   4   5 , Alexander S Whitehead  3   5 , Anil Vachani  1   3   6
Affiliations

Peripheral blood leukocyte mitochondrial DNA content and risk of lung cancer

Gregory T Kennedy et al. Transl Lung Cancer Res. 2022 Jul.

Abstract

Background: Previous studies of peripheral blood leukocyte mitochondrial DNA (mtDNA) content and risk of lung cancer have yielded inconsistent results, and no studies have evaluated the association between mtDNA content and post-resection lung cancer outcomes.

Methods: Using a case-control study design, we evaluated the association between mtDNA content and risk of lung cancer in 465 cases and 378 controls. We also evaluated the association between mtDNA content and survival in 189 cases with surgically resected non-small cell lung cancer (NSCLC). Relative mtDNA content was measured using a quantitative real-time polymerase chain reaction (PCR) assay in peripheral blood genomic DNA. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) using multivariable logistic regression, adjusting for age, gender, race, and smoking history.

Results: mtDNA content was lower in cases compared to controls, with medians of 1.26 [interquartile range (IQR), 0.98-1.70)] and 1.79 (IQR, 1.34-2.10; P<0.001), respectively. Compared to the quartile of subjects with the highest mtDNA content, there was significantly higher likelihood of lung cancer in the second lowest quartile (OR 3.44; 95% CI: 2.06-5.75) and the lowest quartile (OR 6.36; 95% CI: 3.86-10.47). In patients with resected NSCLC, there was no association between lower mtDNA content and recurrence-free survival (RFS) [hazard ratio (HR) 0.89; 95% CI: 0.47-1.66] or overall survival (OS) (HR 0.71; 95% CI: 0.35-1.46).

Conclusions: Thus, our results counter previous studies and find that lower mtDNA content is associated with lung cancer risk. Our results suggest that mtDNA content could potentially serve as a risk biomarker, but is not associated with survival outcomes in NSCLC.

Keywords: Lung cancer; mitochondrial DNA (mtDNA); risk biomarker.

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Conflict of interest statement

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-21-979/coif). GTK reports grant from the National Institutes of Health (Grant F32 CA254210-01) and Daland Fellowship in Clinical Investigation from the American Philosophical Society. TMP, ASW, and AV report grants from the NIH-NIEHS (Grant P30ES013508), and the Pennsylvania Department of Health (Grant PA 4100038714). TMP also reports grant from the NIH-NIEHS (Grant R01ES029294). The other authors have no conflicts of interest to declare.

Figures

Figure 1
Figure 1
OS and RFS. (A) OS by mtDNA content. (B) RFS by mtDNA content. mtDNA, mitochondrial DNA; OS, overall survival; RFS, recurrence-free survival.
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