Objective: Circulating cell-free mitochondrial DNA (cf-MtDNA) has been reported in patients with chronic obstructive pulmonary disease (COPD) and lung cancers. However, inter-relationships among the three biological events have not been well-characterized. Therefore, our investigation was conducted to better understand the role of cf-MtDNA on pathogenesis of the two diseases. Methods: Plasma samples were collected from 64 non-small cell lung cancer (NSCLC) patients (before therapy), 45 patients with COPD and 62 healthy individuals. cf-MtDNA copy numbers were detected using quantitative real-time polymerase chain reaction (qRT-PCR) and cytokines were determined using a human ELISA kit. Results: Our data indicate that smoking statuses of the patients and controls were significantly associated with increased cf-MtDNA in plasma samples. Furthermore, NSCLC patients had significantly higher cf-MtDNA copy numbers than COPD patients (p < 0.03) and normal controls (p < 0.02), together with elevated proinflammatory cytokines over the controls (p < 0.05). Our study shows that the copy numbers for the NSCLC patients were positively associated with their subsequent metastasis but inversely associated with their overall survival. Conclusion:Our study indicates certain lung injury (e.g., from cigarette smoking) was responsible for the release of cf-MtDNA and proinflammatory cytokines into plasmas among our patients and controls. The increase in cf-MtDNA copy numbers was significantly associated with the development of both COPD and NSCLC, with increase in interleukin 6, and from our 5-year follow-up, with poor prognosis among the NSCLC patients. Therefore, with further validation, cf-MtDNA can be considered for use as diagnostic and prognostic biomarkers for NSCLC.

Lung cancer is a problem of great concern and one of the commonest cancer diseases worldwide and in the Republic of Kazakhstan in particular. Radon exposure is classified as the second most important cause of lung cancer. According to the experts, the contribution of natural sources to the average annual radiation dose of the Kazakh population currently stands at 80 %, including 50 % from radon. However, the effect of radon on human health in the Republic of Kazakhstan is almost unknown. The tumor suppressor gene TP53 is a key mediator of the DNA damage response cascade following cell exposure to ionizing radiation. The common polymorphism TP53 Arg72Pro (rs1042522) is a risk factor for lung cancer in the Asian population, but until now no genetic association studies have been done in the Kazakh population. No information on the synergistic carcinogenic effect of radon exposure and polymorphism TP53 Arg72Pro (rs1042522) is available either. This paper presents the results of the study of association between alteration in the TP53 gene and radon-induced lung cancer risk in the Kazakh population. Genetic association was assessed in a case-control study including 44 radon-exposed patients with lung cancer, 41 patients with lung cancer without radon exposure and 42 age/sex-matched healthy controls. We found that polymorphism TP53 Arg72Pro (rs1042522) was associated with lung cancer risk in the Kazakh population (OR = 6.95, 95 % CI = 2.41–20.05). Individuals with the Arg72Pro genotype also showed a significantly higher risk of radon-induced lung cancer (OR = 8.6, 95 % CI = 2.6–28.59).

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