Mechanisms Contributing to the Comorbidity of COPD and Lung Cancer

Abstract

Lung cancer and chronic obstructive pulmonary disease (COPD) often co-occur, and individuals with COPD are at a higher risk of developing lung cancer. While the underlying mechanism for this risk is not well understood, its major contributing factors have been proposed to include genomic, immune, and microenvironment dysregulation. Here, we review the evidence and significant studies that explore the mechanisms underlying the heightened lung cancer risk in people with COPD. Genetic and epigenetic changes, as well as the aberrant expression of non-coding RNAs, predispose the lung epithelium to carcinogenesis by altering the expression of cancer- and immune-related genes. Oxidative stress generated by tobacco smoking plays a role in reducing genomic integrity, promoting epithelial-mesenchymal-transition, and generating a chronic inflammatory environment. This leads to abnormal immune responses that promote cancer development, though not all smokers develop lung cancer. Sex differences in the metabolism of tobacco smoke predispose females to developing COPD and accumulating damage from oxidative stress that poses a risk for the development of lung cancer. Dysregulation of the lung microenvironment and microbiome contributes to chronic inflammation, which is observed in COPD and known to facilitate cancer initiation in various tumor types. Further, there is a need to better characterize and identify the proportion of individuals with COPD who are at a high risk for developing lung cancer. We evaluate possible novel and individualized screening strategies, including biomarkers identified in genetic studies and exhaled breath condensate analysis. We also discuss the use of corticosteroids and statins as chemopreventive agents to prevent lung cancer. It is crucial that we optimize the current methods for the early detection and management of lung cancer and COPD in order to improve the health outcomes for a large affected population.

Single-cell immunophenotyping revealed the association of CD4+ central and CD4+ effector memory T cells linking exacerbating chronic obstructive pulmonary disease and NSCLC

“…Neoantigens were identified in COPD using mass spectrometry supporting the epidemiology data that COPD has been considered as a prestage of lung cancer (7). Non-small cell lung cancer, the most frequent comorbidity, accounts for 40%-70% of COPD patients (8). It was reported that nearly 87% of lung cancerrelated deaths were affected by tobacco smoking in the USA (9).…”

Detection of Volatile Organic Compounds (Voc) in COPD Patients and Its Correlation with Serum Leukotriene B4 and Neutrophil

“…While COPD increase 2 until 7 times fold risk of getting lung cancer. The same mechanism happen both in COPD and lung cancer is oxidative stress [13].…”

Comparison between sodium‐glucose cotransporter 2 inhibitors and dipeptidyl peptidase 4 inhibitors on the risk of incident cancer in patients with diabetes mellitus: A real‐world evidence study

“…Conversely, the finding from the long‐term follow‐up duration is more likely attributed to the pharmacological mechanisms of SGLT‐2i. Compared to DPP‐4i, the prolonged use of SGLT‐2i leads to weight reduction, which may potentially lower the risk of cancer 4,6,9,52–56 . Due to limitations in the database, the present study cannot examine whether the risk of incident cancer decreases with the duration of SGLT‐2i use.…”