Genetic and epigenetic biomarkers of innate immunity in COPD and lung cancer
Chronic obstructive pulmonary disease (COPD) and lung cancer (LC), the most lethal lung diseases, are leading causes of morbidity and mortality worldwide.
They are closely related and share cigarette smoke as a common environmental risk factor. Genetic predisposition is also shared because the fact that only minority of smokers (20%) develop LC or COPD. The presence of COPD, defined as reduced forced expiratory volume in 1 second (FEV1), increases the risk to development of LC up to 4.5-fold, independently of cigarette smoking dosage. The mechanistic explanations of this finding are still poorly understood, likely due to heterogeneous nature of both diseases.
Innate immune response is essential for maintaining lung health and tissue homeostasis but unbalanced inflammation of lungs is associated with diseased conditions, such as COPD and LC. Pulmonary epithelial and immune cells are equipped with diverse pattern recognition receptors (PRRs) able to initiate appropriate innate immune response to invading pathogens or tissue damage associated molecules. It is well documented that excessive inflammation is sufficient to confer risk to both diseases. There is still lack of knowledge how genetic variability of receptors of innate immunity orchestrate inflammation in lungs and how these processes contribute to development of both diseases, on molecular and cellular level.
Also, the histological and molecular heterogeneity of LC, by itself, makes our understanding of carcinogenesis, as well as treatment of disease challenging. Because of global increase in COPD and LC prevalence, strong association of COPD with lung cancer and absence of specific therapeutic targets for both disease, identification of specific gene variants and their involvement in diseased conditions will improve disease treatment at personalized level.
Therefore, the specific aims of this project could be summarized in two work areas:
- Identification of shared genetic and epigenetic risk factors/biomarkers for COPD and LC
- Determination of common mechanistic link of COPD and LC considering the role of innate immunity receptors