Prediction of Susceptibility to COPD Among Cigarette Smokers (original) (raw)

Smoking is the principal modifiable environmental risk factor for chronic obstructive pulmonary disease (COPD) which affects 300 million people and is the 3rd leading cause of death worldwide. Most of the genetic studies of smoking have relied on self-reported smoking status which is vulnerable to reporting and recall bias. Using data from the Lung Health Study (LHS), we sought to identify genetic variants associated with quantitative smoking and cessation in individuals with mild to moderate COPD. The LHS is a longitudinal multicenter study of mild-to-moderate COPD subjects who were all smokers at recruitment. We performed genome-wide association studies (GWASs) for salivary cotinine (n = 4024), exhaled carbon monoxide (eCO) (n = 2854), cigarettes per day (CPD) (n = 2706) and smoking cessation at year 5 follow-up (n = 717 quitters and 2175 smokers). The GWAS analyses were adjusted for age, gender, and genetic principal components. For cotinine levels, SNPs near UGT2B10 gene achieve...

COPD is a heterogenous disease caused by the interaction of genetic susceptibility and environmental influences. The best example to support this is tobacco smoke. Although cigarette smoking is the most important aetiological factor, only up to half of chronic smokers develop significant COPD. There are three main themes within the pathogenesis of COPD: 1) imbalance between proteases and anti-proteases, 2) oxidative stress, 3) inflammation. Disparity between levels of exogeneous oxidants, e. g., tobacco smoke, and endogeneous antioxidants leads to oxidative stress which, in turn, causes an inflammatory response involving pro-inflammatory mediators. The activated inflammatory cells release further proteases and oxidants, leading to chronic inflammation and irreversible destruction of connective tissue in the lung. Individual genetic variations influence these processes in many ways. This article summarises the results of recent candidate gene studies for COPD.

The identification of individuals who are at greatest risk of developing lung cancer would greatly improve diagnosis and possibly lead to early treatment. To study the use of karyotypes for this purpose, we used short-term human bronchial epithelial (hBE) cell cultures from nonsmokers, smokers, and lung cancer patients. Twenty-five metaphases were scored for hBE cell cultures obtained from 32 patients: 8 were nonsmokers, and 24 had a history of smoking (of whom 11 had had lung cancer surgery). The number of abnormal metaphases ranged from 0 to 4 per cell culture. No overall differences in the number of abnormal metaphases were observed between nonsmokers and smokers or between lung cancer patients and non-lung cancer patients. The most commonly observed abnormalities were structural changes in chromosome 1 (six cultures), loss of chromosome 17 (six cultures), and trisomy of chromosome 20 (three cultures). These specific alterations were found almost exclusively in patients with a history of tobacco smoking. The results did not indicate that general chromosomal abnormalities are a useful marker for tobacco smoke exposure or cancer risk.

ABSTRACT COPD is a heterogenous disease caused by the interaction of genetic susceptibility and environmental influences. The best example to support this is tobacco smoke. Although cigarette smoking is the most important aetiological factor, only up to half of chronic smokers develop significant COPD. There are three main themes within the pathogenesis of COPD: 1) imbalance between proteases and anti-proteases, 2) oxidative stress, 3) inflammation. Disparity between levels of exogeneous oxidants, e. g., tobacco smoke, and endogeneous antioxidants leads to oxidative stress which, in turn, causes an inflammatory response involving pro-inflammatory mediators. The activated inflammatory cells release further proteases and oxidants, leading to chronic inflammation and irreversible destruction of connective tissue in the lung. Individual genetic variations influence these processes in many ways. This article summarises the results of recent candidate gene studies for COPD.