Genetic evidence linking lung cancer and COPD: a new perspective
The presence of COPD increases the risk of lung cancer up to fold. communities because several lines of evidence indicate a connection between COPD and lung cancer. .. A prospective, matched, controlled study. COPD and lung cancer share common causes, such as smoking and Keep reading for more on this connection, how it's diagnosed, and what you can do to. A better delineation of the relationships between these three entities may lead to Lung cancer, emphysema, and chronic obstructive pulmonary . obstruction with the risk of lung cancer: a matched case-controlled study.
As an example of the potential impact of this kind of investigation, a recent analysis of gene expression profiling of nontumor—involved lung tissue from COPD patients who underwent lung tissue resection for lung cancer showed selective regulation of specific signaling pathways and highlighted new potential therapeutic targets The role of epigenetic modifications in the common pathogenesis of COPD and lung cancer also deserves attention.
Although there is growing evidence implicating DNA methylation, histone deacetylation, and protein phosphorylation in lung cancer pathogenesis 33—35this knowledge is only now being applied to COPD, alone or when associated with lung cancer 36 It is plausible that several candidate risk genes and pathways identified by lung cancer studies may be shared by these two diseases and could constitute potential targets for the newly developed drugs eg, demethylating agents and histone deacetylase—inhibiting agents that modify epigenetic alterations.
Pathological Considerations Diagnosis of COPD is generally confirmed by physiological testing spirometry that assesses the presence of an airflow limitation that is not fully reversible with the use of a bronchodilator Loss of elastic recoil and airway inflammation are also characteristic features of the disease, but it is the small airway thickening in all three of its components epithelium, lamina propria, and adventitia that is most strongly associated with airflow obstruction 39— Lung cancer, by contrast, occurs in several different histological types, possibly reflecting the highly complex structure of the organ from which it originates.
Although squamous cell carcinomas and SCLC are often centrally located in the airwaysadenocarcinomas and large cell carcinomas are typically of peripheral origin. This rather simplified classification into two basic types becomes much more complex when molecular biology studies are applied to further distinguish the lesions by their phenotype 43 Knowledge of the early molecular events that lead to squamous cell carcinomas is growing 45but little is known about the early molecular events that lead to the development of other types of lung carcinoma.
As a practical consequence of the epidemiological associations between COPD and lung cancer, an important question is whether the relationship between lung cancer and COPD is subtype specific. In a subset analysis, having concurrent bronchitic symptoms and COPD was associated with a more than threefold increased risk for squamous cell carcinoma.
Another study 47 showed that increased risk of lung cancer was more strongly associated with the presence of computed tomography—diagnosed emphysema than with spirometric-diagnosed airway obstruction, a finding that was confirmed in a US cohort Cytological atypia is associated with substantial risk of lung cancer, but there is no association between the severity of atypia and the degree of airflow obstruction 49 despite the high incidence of sputum dysplasia in subjects with airflow obstruction A molecular analysis of preneoplastic lesions in the central or peripheral airways has contributed to the delineation of different carcinogenetic pathways For example, a generalized hyperactivation of the translational machinery appears to be required for maintenance of the malignant phenotype in lung cancer and triggers the epithelial-to-mesenchymal transition EMTa process in which cells undergo a switch from an epithelial phenotype to a mesenchymal phenotype 53— Recent studies indicating that inflammation directly promotes EMT by inducing the expression of E-cadherin transcriptional repressors belonging to the zinc-finger family 5859 provide evidence of additional connections between these diseases.
These findings can explain how abnormal inflammation is related to both COPD and lung cancer 60 Recent histopathological and clinical analyses show that COPD is associated with abnormal inflammatory features both in the lungs and systemically 40 Similarly, the connection between inflammation and cancer development is an old concept that has its roots in the comparison of the tumor with a wound that does not repair.
Virchow's hypothesis that cancer occurs at sites of chronic inflammation is now well established 63— A mechanistic understanding of these associations is now emerging as studies have shown that manipulation of prostaglandin production can affect both lung carcinogenesis and growth factor—driven pathways.
COPD and Lung Cancer: Does One Lead to the Other?
These findings have led to several experimental trials of chemoprevention 66— Conversely, inflammatory elastinolytic activity, which is essential in driving emphysema progression, is also capable of suppressing the growth of lung metastases 69 Conclusion In this large population-based cohort, a concurrent asthma diagnosis and use of inhaled corticosteroids were independently related to decreased risk of lung cancer in COPD patients, while the use of acetylsalicylic acid was associated with an increased risk.
The findings of the present study should be seen as hypothesis generating and need to be confirmed in prospective studies. Recent findings in animal studies have pointed toward a new and potentially detrimental role of NAC and an increased risk of lung cancer occurrence.
The aim of our study was to investigate the factors associated with lung cancer in a large cohort of COPD patients in a primary care setting, with special emphasis on the role of pharmacological treatments and comorbidities.
Methods To analyze whether comorbidity and continuous use of medication affect the risk of lung cancer development in COPD, we used a large COPD cohort of primary care patients.
The primary health care centers from which patient data were obtained were chosen to reflect a mixture of rural and urban areas, public and private health care providers, and center sizes.
However, no formal stratification of health care providers was performed. Additional patient information was collected from mandatory Swedish national registries. Morbidity and mortality, inpatient admission and discharge dates, and main and secondary diagnoses and outpatient hospital care number of contacts and diagnoses according to ICDCM codes data were collected from the National Patient Register.
Date and cause s of death were obtained from the Cause of Death Register. The Swedish Prescribed Drug Register was used to acquire data regarding drug prescriptions from hospital and primary care during the study period. The study was registered at ClinicalTrials.
Factors associated with lung cancer in COPD patients
Patient consent was not required by the committee as all data was anonymized. Study population and outcome variables From the chosen primary care centers, men and women with physician-diagnosed COPD ICDCM code J44 in medical records or national registers were included in the study. Patients who had physician-diagnosed COPD any time from January 1,to December 31,were eligible for inclusion and the index date was defined as date of first COPD diagnosis.
Patients were followed until December 31,emigration or death. Comorbidities were analyzed in regard to ICDCM diagnoses registered in medical records or national registers, and for patients with lung cancer before this diagnosis appeared in the register. The following comorbidities were included: Prescription events were analyzed for pack-size and prescribed daily dose related to predefined Anatomical Therapeutic Chemical Classification System groups.
Data on use of medication were collected from the period 2 years prior to COPD diagnosis until the end of the observation period December 31,emigration or death. To analyze any exposure-dependency, a relative exposure was calculated as the proportion of days covered of the drug of interest, during a time interval of at least 2 years starting 2 years prior to index.
- Genetic evidence linking lung cancer and COPD: a new perspective
- Impact of COPD on prognosis of lung cancer: from a perspective on disease heterogeneity
- Factors associated with lung cancer in COPD patients
Drug exposure was included as a time varying covariate updated once every year.