Abstract 879: Mitochondrial DNA content and its association with lung cancer risk and clinical outcomes

Mitochondrion is an essential cellular organelle generating energy, and also plays a key role in the initiation and regulation of apoptosis. Impaired mitochondria function may inhibit apoptosis; enhance reactive oxygen species and generate cancer related proteins. The difference in mitochondrial DNA (mtDNA) content (also termed mtDNA copy number) may contribute to cancer predisposition as well as variations in clinical outcomes. To test this hypothesis, we conducted a large-scale case-control study to investigate the role of mtDNA content in lung cancer etiology and clinical outcomes. MtDNA content in 2,442 newly diagnosed lung cancer patients and 2,417 matched controls were measured by quantitative real-time polymerase chain reaction. Clinical outcome data were collected for non-small cell lung cancer (NSCLC) patients (2,020 subjects). We analyzed the association of MtDNA copy number with the risk of developing lung cancer and also the clinical outcomes in NSCLC patients. MtDNA content was significantly lower in patients than controls (mean=1.17 vs. 1.23, P=4.28×10−4). Compared to higher mtDNA content (above the median value in the controls), lower mtDNA content was associated with a significantly increased risk for lung cancer (OR=1.25, 95%CI=1.11-1.41, P=1.52×10−4). In the trend analysis, we detected a significant dose-response relationship between mtDNA content and risk, as lower mtDNA content was associated with a progressively increased risk for lung cancer (P-trend=1.40×10−4). In the analysis of clinical outcomes, a significant difference in mtDNA content was observed between death and survival groups (mean=1.12 vs. 1.27, P=6.62×10−4) in early stage (stage I and II) NSCLC patients. Compared to those who have higher mtDNA content, patients who have lower mtDNA content had a 45% higher risk for death (HR=1.34, 95%CI=1.05-1.71, P=0.019), and a dramatically shorter survival time (58 months vs. 96 months, log-rank P=5.68×10−4). A dose-response effect of increased risk for death was found with decreased mtDNA content (P-trend=0.048) in this group of patients. No significant results were found in advance stage (stage III and IV) patients. To our knowledge, this is the first study to evaluate the association of MtDNA copy number with lung cancer risk and clinical outcomes. Our results suggested that lower mtDNA content is associated with increased lung cancer risk and poor prognosis in early stage NSCLC patients. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 879.