Abstract 4509: Mitochondrial DNA copy number is inversely associated with overall survival in non-small cell lung cancer

Abstract

Abstract Mitochondria play an important role in generating energy for vital cellular functions. Alterations in mitochondria function due to mutations or copy number changes can potentially lead to tumorigenesis. Although previous studies have investigated the effect of mitochondrial DNA (mtDNA) depletion on cancer risk, no studies have assessed constitutive mtDNA copy number as a prognostic marker for overall survival in non-small cell lung cancer (NSCLC). Towards this, we measured mtDNA content by a quantitative real-time PCR assay in peripheral blood lymphocytes collected prior to treatment from 1,134 NSCLC cases seen at MD Anderson Cancer Center. A significant inverse dose-response trend was identified for mtDNA content and NSCLC risk (p-value: 0.0076). Those with the highest tertile of mtDNA content had the greatest reduction in risk of dying (HR: 0.81, 95% CI: 0.82-0.97, p-value: 0.014) and a highly significantly enhanced median survival time of 20.20 months compared to only 14.11 months for those with the lowest mtDNA content (p-value: 6.7x10-5). It is known that exposure to tobacco smoke results in the production of reactive oxygen species that can damage mtDNA. Therefore, we also performed stratified analysis based on smoking status. The effect in ever smokers (N=951) mirrored that of the overall population with a significant reduction in risk of death with increasing mtDNA content (p-trend: 0.008) and a dramatic nearly seven month survival advantage for those patients with the highest mtDNA content compared to the lowest (20.73 months compared to 13.98 months, respectively, p-value: 4.1x10-5). Interestingly, mtDNA content was not significant with overall survival in never smokers (N=183), suggesting that the effect in the overall population was driven by the ever smokers and that mtDNA alterations do not play a major role in the course of disease for this unique subgroup of NSCLC patients. Together, these results demonstrate that mtDNA content is a potential prognostic biomarker in NSCLC that can be measured non-invasively prior to treatment to provide needed information regarding course of disease to identify those at high risk for a poor outcome. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4509. doi:1538-7445.AM2012-4509