Interaction was examined between smoking and each of four factors previously found to be related to AO: alpha-1 antitrypsin (PiZ allele), ABO blood groups (A antigen), ABH non-secretor status, and first degree relationship to a COPD or lung cancer patient.
Despite the known associations of alpha1-antitrypsin deficiency (alpha1AD) with COPD and COPD with LC, few studies examined the association of alpha1AD alleles and LC.
Sex and ethnicity were comparable between case patients and control subjects, but case patients were more likely to be smokers, and to have a history of COPD, environmental tobacco smoke exposure, and a positive family history of lung cancer.
Here we discuss the current understanding of miRNA involvement in innate immunity, specifically in LPS/TLR4 signalling and in the progression of the chronic inflammatory lung diseases cystic fibrosis, COPD and asthma. miRNA in lung cancer and IPF are also reviewed.
Strategies to study genomics, epigenomics and gene-environment interaction will yield greater insight into the shared pathogenesis of lung cancer and COPD, leading to new diagnostic and therapeutic modalities.
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.
Scope of Proposed Topic (50 words): Genome-wide association (GWA) studies both in lung cancer and COPD highlighted the same variants (SNPs) on the gene cluster CHRNA3-CHRNB4-CHRNA5.
Resected lung from patients with COPD undergoing lung cancer surgery was profiled using miRNA (Agilent Human miRNA profiler G4470 V1.01) and mRNA (OperonV2.0) microarrays.
COPD and lung cancer are strictly related; to date it is unknown if COPD-associated cancers have different features from tumours arising in non-COPD patients.
Alternatively COPD could be a driving factor in lung cancer, by increasing oxidative stress and the resulting DNA damage, chronic exposure to pro-inflammatory cytokines, repression of the DNA repair mechanisms and increased cellular proliferation.
Our study demonstrated that KRAS 3'-UTR rs712 polymorphism interfered with miRNA/mRNA interaction, and showed that the minor allele was associated with an elevated risk for development of lung cancer in COPD.
MiRNAs that were identified as relevant for the separation between lung cancer and COPD by both qRT-PCR and the array-based studies included hsa-miR-26a-5p, hsa-miR-328-3p and hsa-miR-1224-3p.
These studies indicate that sustained activation of NF-κB pathway links COPD and lung cancer through generation and maintenance of a pro-tumorigenic inflammatory environment consisting of alternatively activated macrophages and regulatory T cells.
The defining and understanding of COPD-lung cancer transformation will provide new diagnostic and therapeutic biomarkers as a new milestone to prevent and treat lung cancer.
COPD infradiagnosis is common in patients with coexisting lung cancer and is associated with more advanced cancer stage, greater outpatient resource consumption, and may be associated with greater stage-adjusted mortality.