RT Journal Article
SR Electronic
T1 Late-breaking abstract: The TERT-CLPTM1L locus for lung cancer predisposes to bronchial obstruction and emphysema
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP 1700
VO 38
IS Suppl 55
A1 Els Wauters
A1 Dominiek Smeets
A1 Johan Coolen
A1 Johny Verschakelen
A1 Paul De Leyn
A1 Marc Decramer
A1 Johan Vansteenkiste
A1 Wim Janssens
A1 Diether Lambrechts
YR 2011
UL http://erj.ersjournals.com/content/38/Suppl_55/1700.abstract
AB Clinical studies suggest that bronchial obstruction and emphysema increase susceptibility to lung cancer. We assess the possibility of a common genetic origin and investigate whether the lung cancer susceptibility locus on chromosome 5p15.33 increases the risk for bronchial obstruction and emphysema.Three variants in the 5p15.33 locus encompassing the TERT and CLPTM1L genes were genotyped in 777 heavy smokers and 212 lung cancer patients. Participants underwent pulmonary function tests and computed tomography (CT) of the chest, and took questionnaires assessing smoking behaviour.The rs31489 C-allele correlated with reduced forced expiratory volume in 1 second (FEV1; P=0.006). Homozygous carriers of the rs31489 C-allele exhibited increased susceptibility to bronchial obstruction with an odds ratio (OR) of 1.82 (95% confidence interval [CI]=1.24-2.69; P=0.002). A similar association was noticed for lung diffusing capacity (DLCO; P=0.004). Consistent herewith, CC-carriers had an increased risk of emphysema (OR=2.04; CI=1.41-2.94; P=1.73×10-4) and displayed more alveolar destruction. Finally, CC-carriers also had an increased risk for lung cancer (OR=1.90; CI=1.21-2.99; P=0.005) and were more susceptible to develop both lung cancer and bronchial obstruction than lung cancer alone (OR=2.11; CI=1.04-4.26; P=0.038).The rs31489 variant on 5p15.33 is associated with bronchial obstruction, the presence and severity of emphysema and lung cancer.