Mitochondrial DNA Copy Numbers and Lung Cancer: A Systematic Review and Meta-Analysis

LC continues to be the leading cause of cancer mortality globally, among both males and females, representing a major public health challenge. The impact of mitochondria on human health and disease is a rapidly growing focus in scientific research, due to their critical roles in cellular survival and death. Mitochondria play an important role in controlling imperative cellular parameters, and alterations in mtDNAcn might be crucial for LC development. MtDNAcn has been studied as a possible marker for LC risk, but its role in prevention is still unclear. This review and meta-analysis aims to summarize the current evidence and provide an overall estimate of the relationship between the mtDNA copy number in human samples like blood and sputum. PubMed, Web of Science, and Scopus databases were used for studies published up to February 2024, following PRISMA and MOOSE guidelines. Studies were combined using a random-effects model, and we assessed the heterogeneity between studies with the chi-square-based Cochran's Q statistic and the I² statistic. Publication bias was checked using Begg's and Egger's tests. Five studies, including a total of 3.748 participants, met the eligibility criteria. The MtDNA copy number was measured in blood or sputum samples and compared across different quantiles. The pooled analysis did not find a significant association between the mtDNA copy number and LC risk (OR = 0.94; 95% CI: 0.49-1.78). Moreover, when looking at different study designs, no significant results were found, due to the small number of studies available. No significant publication bias was detected. Further studies are needed to better understand the connection between the mtDNA copy number and LC risk and to better understand the role of potential confounders.