Lung Cancer in Chronic Obstructive Pulmonary Disease Patients, It Is Not Just the Cigarette Smoke

Pablo Sanchez-Salcedo; Javier J. Zulueta


Curr Opin Pulm Med. 2016;22(4):344-349. 

In This Article

Abstract and Introduction


Purpose of review An important association has been described between chronic obstructive pulmonary disease (COPD) and lung cancer, where different mechanisms have been proposed. There is no unique cause for this association, as COPD is by itself a heterogeneous disease, in which their classical phenotypes (i.e., emphysema and chronic bronchitis) each play an important role in lung cancer development. We will discuss recent evidence that links these two diseases and specific characteristics found in lung cancers from patients with COPD.

Recent findings Molecular studies have found specific gene expressions (reduction and overexpression) in lung tumors from patients with COPD, which likely predispose to increased methylation during lung carcinogenesis, and are associated with aggressiveness. Recent evidence suggests that lung cancer risk is higher in individuals with long telomeres, and that this effect takes place well in advance of diagnosis. Lung cancer is likely to develop in areas of the lung with greater emphysema and the severity of the latter is associated with larger and more aggressive tumors.

Summary Clinical and molecular studies have found that lung cancers that develop in patients with COPD and/or emphysema appear to be more aggressive and have a distinct molecular profile when compared with tumors from patients without an underlying lung disease. This could have important implications when deciding on personalized treatments.


Lung cancer and chronic obstructive pulmonary disease (COPD) are among the deadliest diseases worldwide, after gaining positions as leading causes of death over the past 20 years.[1] Tobacco exposure is one element these two diseases have in common, but the fact that only a minority of smokers develop lung cancer, COPD, or both, highlights the importance of genetic susceptibility to disease or other unknown factors.[2] Several epidemiological studies have described a strong association between these diseases, where chronic inflammation and lung repair mechanisms, present in patients with COPD, appear to be key features.[3]

COPD is defined as the presence of airflow obstruction [postbronchodilator fixed ratio of forced expiratory volume (FEV1) in 1 s and forced vital capacity <0.70].[4] Even though when we refer to COPD, we usually make reference to it as a whole, this disease has two well differentiated phenotypes, namely chronic bronchitis and emphysema. Evidence on the association between COPD and lung cancer over the past 30 years has initially focused on airflow obstruction, with a transition to emphysema during the last decade due to a widespread use of computed tomography (CT). Furthermore, specific lung cancer features have been described in patients with COPD and emphysema that are neither present in lung cancer patients without airflow obstruction nor emphysema. We will present several potential mechanisms that link these two diseases and evidence-associating COPD and lung cancer.