How the genetics of lung cancer may overlap with COPD

Abstract

Over the last 30years, epidemiological studies have shown that COPD is the single most important risk factor for lung cancer after smoking exposure. Recent genetic studies using genome-wide approaches suggest that the genetic risk factors predisposing smokers to COPD and lung cancer may overlap. The genes identified by these studies suggest that this overlapping genetic susceptibility may be mediated through receptors expressed on the bronchial epithelium that implicate molecular pathways underlying both COPD and lung cancer. Furthermore, it appears that aberrant inflammatory and/or immune-modulatory pathways leading to excess matrix metalloproteinases, growth factors and airway remodelling in COPD may also be promoting malignant transformation of the bronchial epithelium. The process linking inflammation, remodelling and cancer formation is called epithelial-mesenchymal transition. There are several clinical implications arising from the COPD-lung cancer overlap. First, if COPD is a precursor disease to lung cancer then efforts to prevent COPD, might be even more important. Second, if drugs targeting the overlapping molecular pathways can be identified, chemoprevention that reduce the propensity to COPD and lung cancer is an attractive option. Finally, if low-dose computerized tomography can identify treatable lung cancer, gene-based tests of susceptibility might help identify those smokers who should undergo radiological screening.