Mechanistic links between COPD and lung cancer

Numerous epidemiological studies have consistently demonstrated an increased incidence of lung cancer in patients who have chronic obstructive pulmonary disease (COPD).The emphysema component of COPD, which is characterized by excessive inflammation and matrix destruction, is sufficient to confer an increased risk for lung cancer. Taken together, the epidemiological literature suggests that entities involved in the airways and airspace components of COPD are both operative in increasing lung cancer risk.Both COPD and lung cancer involve a substantial role for genetic susceptibility to disease, as only a minority of chronic cigarette smokers will develop one, or both, of the diseases. Several single nucleotide polymorphisms (SNPs) in candidate gene families (for example, detoxifying enzymes, proteinases, anti-proteinases and cytokines) have been implicated in disease pathogenesis for both COPD and lung cancer, and may confer a proportion of the risk.The oxidant and noxious stress encountered in the lungs of cigarette smokers is overwhelming. These species cause sufficient damage to some epithelial cells such that they undergo apoptosis, resulting in emphysema. They additionally represent genotoxic stress capable of DNA adduct formation, thereby promoting the earliest stages of carcinogenesis.Inflammatory cell infiltrates are common to both COPD and lung cancer. Their quantity and quality must be taken in context. Inflammation encountered in emphysema is typically cytotoxic and destructive to matrix structures. Such cells would not be expect to promote the growth of an existing tumour, but would provide the necessary genotoxic stress for tumour initiation. Once formed, small tumours polarize immune cells to alternatively activated phenotypes, which promote tumour growth and angiogenesis.Matrix-degrading enzymes, especially those capable of degrading elastin (elastases) are essential for the development of emphysema. Many of these enzymes have been shown to promote lung tumour growth by a variety of mechanisms, including enhanced cellular proliferation and increased angiogenesis, which permits endovascular invasion. Therefore, these enzymes are likely to represent a proportion of the link between emphysema and lung cancer.As operative mechanisms linking COPD to lung cancer are discovered, the opportunity for chemoprevention will arise. Ideally, new therapies will be developed that have the ability to retard COPD progression while reducing lung cancer risk.