We performed a nested case-control study of Genetic Epidemiology of COPD (COPDGene) Study subjects with and without lung cancer, age 45 to 80 years, who smoked at least 10-pack years to identify clinical and imaging features of smokers, with and without COPD, that are associated with an increased risk of lung cancer.
Preferring relative risks adjusted for daily amount smoked, where adjusted and unadjusted estimates were available, combined estimates for lowest versus highest tar (or nicotine) groups were 0.78 (95% confidence interval 0.70-0.88) for lung cancer, 0.86 (0.81-0.91) for heart disease, 0.77 (0.62-0.95) for stroke and 0.81 (0.65-1.02) for COPD.
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.
Transforming growth factor (TGF)-β1 has been implicated in the pathogenesis of COPD, and in particular a process called epithelial mesenchymal transition (EMT), which may well be an intermediatory between smoking and both airway fibrosis and lung cancer.
We identified 50 eligible studies.We found that waterpipe tobacco smoking was significantly associated with: respiratory diseases [COPD; odds ratio (OR) = 3.18, 95% confidence interval CI = 1.25, 8.08; bronchitis OR = 2.37, 95% CI = 1.49, 3.77; passive waterpipe smoking and wheeze OR) = 1.97, 95% CI = 1.28, 3.04]; oral cancer OR = 4.17, 95% CI = 2.53, 6.89; lung cancer OR = 2.12, 95% CI = 1.32, 3.42; low birthweight (OR = 2.39, 95% CI = 1.32, 4.32); metabolic syndrome (OR 1.63-1.95, 95% CI = 1.25, 2.45); cardiovascular disease (OR = 1.67, 95% CI = 1.25, 2.24); and mental health (OR 1.30-2.4, 95% CI = 1.20, 2.80).
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.
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.
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.
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.
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.