The relationship between COPD and lung cancer

Abstract

Both COPD and lung cancer are major worldwide health concerns owing to cigarette smoking, and represent a huge, worldwide, preventable disease burden. Whilst the majority of smokers will not develop either COPD or lung cancer, they are closely related diseases, occurring as co-morbidities at a higher rate than if they were independently triggered by smoking. Lung cancer and COPD may be different aspects of the same disease, with the same underlying predispositions, whether this is an underlying genetic predisposition, telomere shortening, mitochondrial dysfunction or premature aging. In the majority of smokers, the burden of smoking may be dealt with by the body's defense mechanisms: anti-oxidants such as superoxide dismutases, anti-proteases and DNA repair mechanisms. However, in the case of both diseases these fail, leading to cancer if mutations occur or COPD if damage to the cell and proteins becomes too great. Alternatively COPD could be a driving factor in lung cancer, by increasing oxidative stress and the resulting DNA damage, chronic exposure to pro-inflammatory cytokines, repression of the DNA repair mechanisms and increased cellular proliferation. Understanding the mechanisms that drive these processes in primary cells from patients with these diseases along with better disease models is essential for the development of new treatments.

Keywords: COPD; Cancer; ROS.

Fig. 1

Reactive oxygen and nitrogen species (RNOS) derived from both exogenous and endogenous sources drive many of the pathways in both COPD and lung cancer. RNOS can react with DNA, leading to DNA damage, which if not correctly repaired leads to mutations. Mechanisms that prevent mutation, including DNA repair and apoptosis can be inhibited by RNOS activity. Additionally RNOS can contribute to susceptibility to infection and drive inflammation in the lungs. Inflammation can lead to further cellular and DNA damage, both through the generation of further RNOS and also through the action of cytokines and proteases. RNOS are capable of inhibiting the protective mechanisms, such as anti-proteases. Damage to the lungs is repaired by processes including cellular proliferation, which can in turn promote tumourgenesis.