Genomic instability in chronic obstructive pulmonary disease and lung cancer: A systematic review and meta-analysis of studies using the micronucleus assay

Abstract

Respiratory tissues are highly susceptible to diseases due to the constant exposure to physical and chemical airborne pollutants. Chronic obstructive pulmonary disease (COPD) and lung cancer are among the most common causes of serious illness and death worldwide. The inflammatory environment associated with these respiratory diseases has long been accepted as the major player in the development of airway abnormalities. The presence and relevance of DNA damage and genomic instability makes the micronucleus assay a suitable candidate to quantitatively estimate these early pathogenetic events. A systematic review and meta-analysis were planned to determine underlying common mechanisms that can explain the relationships between COPD and lung cancer. A total of 17 studies from Jan 1999 to Dec 2019 comparing micronucleus frequency in patients affected by respiratory diseases vs healthy controls were analysed. Our results confirmed the presence of significant association between MN frequency and the diseases investigated, and suggested a circle of events linking inflammation induced oxidative stress to the risk of disease through genomic instability and hypoxia. Therefore, using non-invasive, robust and cost effective genomic instability assays such as the micronucleus assay, would allow us to capture unique phenotypic and biological changes that would allow the identification of subjects at high risk of developing lung diseases and improve early detection strategies.