Chronic Obstructive Pulmonary Disease and Risk of Lung Cancer: The Importance of Smoking and Timing of Diagnosis

Powell, Helen; Iyen, Barbara; Baldwin, David R; Hubbard, Richard; Tata, Laila J.

doi:10.1097/jto.0b013e318274a7dc

Cited by 90 publications

(64 citation statements)

References 18 publications

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“…Cigarette smoke remains the main common risk factor between both diseases; however, the diagnosis of COPD, even in neversmokers, is associated with a greater than 2-fold increased risk of lung cancer compared with patients without COPD (2). This suggests that shared biological mechanisms play a role in the development of both diseases.…”

mentioning

confidence: 97%

Cigarette Smoke Activates the Proto-Oncogene c-Src to Promote Airway Inflammation and Lung Tissue Destruction

Geraghty

Hardigan

Foronjy

2014

Am J Respir Cell Mol Biol

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The diagnosis of chronic obstructive pulmonary disease (COPD) confers a 2-fold increased lung cancer risk even after adjusting for cigarette smoking, suggesting that common pathways are operative in both diseases. Although the role of the tyrosine kinase c-Src is established in lung cancer, less is known about its impact in other lung diseases, such as COPD. This study examined whether c-Src activation by cigarette smoke contributes to the pathogenesis of COPD. Cigarette smoke increased c-Src activity in human small airway epithelial (SAE) cells from healthy donors and in the lungs of exposed mice. Similarly, higher c-Src activation was measured in SAE cells from patients with COPD compared with healthy control subjects. In SAE cells, c-Src silencing or chemical inhibition prevented epidermal growth factor (EGF) receptor signaling in response to cigarette smoke but not EGF stimulation. Further studies showed that cigarette smoke acted through protein kinase C a to trigger c-Src to phosphorylate EGF receptor and thereby to induce mitogen-activated protein kinase responses in these cells. To further investigate the role of c-Src, A/J mice were orally administered the specific Src inhibitor AZD-0530 while they were exposed to cigarette smoke for 2 months. AZD-0530 treatment blocked c-Src activation, decreased macrophage influx, and prevented airspace enlargement in the lungs of cigarette smoke-exposed mice.Moreover, inhibiting Src deterred the cigarette smoke-mediated induction of matrix metalloproteinase-9 and -12 in alveolar macrophages and lung expression of cathepsin K, IL-17, TNF-a, MCP-1, and KC, all key factors in the pathogenesis of COPD. These results indicate that activation of the proto-oncogene c-Src by cigarette smoke promotes processes linked to the development of COPD.

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confidence: 97%

Cigarette Smoke Activates the Proto-Oncogene c-Src to Promote Airway Inflammation and Lung Tissue Destruction

Geraghty

Hardigan

Foronjy

2014

Am J Respir Cell Mol Biol

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“…Of 11,888 incident cases of lung cancer, 23 % had a prior diagnosis of COPD compared with only 6 % of the 37,605 controls (Powell et al 2013). The prevalence of COPD in lung cancer patients varies from 8 to 50 %, and the annual incidence of lung cancer arising from COPD is 0.8-1.2 %.…”

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confidence: 99%

New biomarkers and therapeutics can be discovered during COPD-lung cancer transition

Wang

2016

Cell Biol Toxicol

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Chronic obstructive pulmonary disease (COPD) has been found to be associated with lung cancer regardless of a patient's smoking history. Of 11,888 incident cases of lung cancer, 23 % had a prior diagnosis of COPD compared with only 6 % of the 37,605 controls (Powell et al. 2013). The prevalence of COPD in lung cancer patients varies from 8 to 50 %, and the annual incidence of lung cancer arising from COPD is 0.8-1.2 %. This indicates that ∼1 % of COPD patients develop lung cancer each year, while only 0.2 % of patients with normal pulmonary function develop lung cancer. The Environment and Genetics in a Lung Cancer Etiology population-based case-control study showed that lung cancer risk was increased among individuals with chronic bronchitis, emphysema, and COPD (Sekine et al. 2012). COPD co-exists with 40-70 % of lung cancer patients, and 50 % of newly diagnosed lung cancer patients had COPD whereas only 8 % of smokers without lung cancer had COPD. Smokers with COPD are more susceptible to lung cancer.Epidemiological studies indicate that tobacco smoke exposure accounts for nearly 90 % of cases of COPD and lung cancer. However, genetic factors may explain why 10-30 % of smokers develop to COPD, even though genetic network and gene set enrichment in cigarette smoking were found to be correlated with the development of lung cancer (Fang et al. 2013). COPD is closely linked to susceptibility to lung cancer and acts as the most important risk factor for lung cancer among smokers, predating lung cancer in up to 80 % of cases. Genome-wide association studies on lung cancer, lung function, and COPD have identified a number of overlapping Bsusceptibility^loci. With stringent phenotyping, several overlapping loci are independently associated with both COPD and lung cancer, but with pulmonary inflammation and apoptotic processes mediated by the bronchial epithelium (Bondarczuk and PiotrowskaSeget 2013;Corbel et al. 2002;Bao et al. 2016a). Some lung cancer-specific genetic variants were identified as BCOPD-related^genetic variants associated with clinical variables (Young et al. 2011).Gene and protein expression profiles were initially investigated among patients with stable COPD, acute exacerbation of COPD (AECOPD), COPD with or without smoking, and COPD with or without lung cancer, to compare with those of healthy or health smokers (Chen et al. 2012). A number of disease-, stage-, duration-, or therapy-specific biomarkers were selected to screen susceptible populations of COPD or lung cancer. Using clinical bioinformatic techniques, the specificity, biological function, or prevalence of selected target genes or proteins from patients with AECOPD were furthermore validated in association with different types, survival rate, or potential mechanism of lung cancer (Ye et al. 2015). Chronic inflammation associated with COPD likely plays a role in the pathogenesis of lung cancer, and acute exacerbation can be the critical factor in the tumorigenesis of lung cancer. Inflammation

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“…It is well known that lung transplant candidates with chronic obstructive lung disease (COPD) and idiopathic pulmonary fibrosis (IPF) are at high risk of developing lung cancer as a result of previous exposure to cigarette smoking (35)(36)(37). In a recent study by the Toronto Lung Transplant group, unexpected lung cancer was diagnosed in explanted lungs in 13/853 (1.52%) of all transplants performed between 2003 and 2012.…”

Section: Primary Lung Cancermentioning

confidence: 99%

Lung cancer: a rare indication for, but frequent complication after lung transplantation

Raemdonck¹,

Vos²,

Yserbyt³

et al. 2016

J. Thorac. Dis.

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Lung transplantation is an effective and safe therapy for carefully selected patients suffering from a variety of end-stage pulmonary diseases. Lung cancer negatively affects prognosis, particularly in patients who are no longer candidates for complete resection. Lung transplantation can be considered for carefully selected and well staged lung cancer patients with proven, lung-limited, multifocal, (minimally invasive) adenocarcinoma in situ (AIS) (previously called bronchioloalveolar cell carcinoma) causing respiratory failure. Despite a substantial risk of tumour recurrence (33-75%), lung transplantation may offer a survival benefit (50% at 5 years) with best palliation of their disease. Reports on lung transplantation for other low-grade malignancies are rare. Lung transplant candidates at higher risk for developing lung cancer [mainly previous smokers with chronic obstructive lung disease (COPD) and idiopathic pulmonary fibrosis (IPF) or older patients] should be thoroughly and repeatedly screened for lung cancer prior to listing, and preferably also during waiting list time if longer than 1 year, including the use of PET-CT scan and EBUS-assisted bronchoscopy in case of undefined, but suspicious pulmonary abnormalities. Double-lung transplantation should now replace single-lung transplantation in these high-risk patients because of a 6-9% prevalence of lung cancer developing in the remaining native lung. Patients with unexpected, early stage bronchial carcinoma in the explanted lung may have favourable survival without recurrence. Early PET-CT (at 3-6 months) following lung transplantation is advisable to detect early, subclinical disease progression. Donor lungs from (former) smokers should be well examined at retrieval. Suspicious nodules should be biopsied to avoid grafting cancer in the recipient. Close follow-up with regular visits and screening test in all recipients is needed because of the increased risk of developing a primary or secondary cancer in the allograft from either donor or recipient origin.

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Chronic Obstructive Pulmonary Disease and Risk of Lung Cancer: The Importance of Smoking and Timing of Diagnosis

Cited by 90 publications

References 18 publications

Cigarette Smoke Activates the Proto-Oncogene c-Src to Promote Airway Inflammation and Lung Tissue Destruction

Cigarette Smoke Activates the Proto-Oncogene c-Src to Promote Airway Inflammation and Lung Tissue Destruction

New biomarkers and therapeutics can be discovered during COPD-lung cancer transition

Lung cancer: a rare indication for, but frequent complication after lung transplantation

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