RT Journal Article SR Electronic T1 Lung cancer gene associated with COPD: triple whammy or possible confounding effect? JF European Respiratory Journal JO Eur Respir J FD European Respiratory Society SP 1158 OP 1164 DO 10.1183/09031936.00093908 VO 32 IS 5 A1 Young, R. P. A1 Hopkins, R. J. A1 Hay, B. A. A1 Epton, M. J. A1 Black, P. N. A1 Gamble, G. D. YR 2008 UL http://erj.ersjournals.com/content/32/5/1158.abstract AB Recently, several large genome-wide association studies have identified a putative “lung cancer” locus in the nicotinic acetylcholine receptor subunit genes (nAChR) on 15q25. However, these findings may be confounded by the presence of chronic obstructive pulmonary disease (COPD), which is also strongly associated with smoking exposure and lung cancer. This is likely as the prevalence of COPD in lung cancer cohorts is as much as two-fold greater than that reported in smoking control populations (50 versus 20%). The present authors compared the genotype frequencies of the most strongly associated single nucleotide polymorphism (rs16969968) in the α5 subunit of the nAChR gene cluster between three matched smoking cohorts. The AA genotype was found to be more frequent and was seen in 437 (16%) lung cancer cases and 445 (14%) COPD cases compared with 475 (9%) healthy smoking controls. More importantly, when 429 lung cancer cases were divided according to spirometry results (performed within 3 months of diagnosis, prior to surgery and in the absence of effusions or collapse), the AA genotype was present in 19 and 11% of cases with and without COPD, respectively. These findings suggest that the association between the α5 subunit nicotinic acetylcholine receptor single nucleotide polymorphism and lung cancer may, in part, be confounded by chronic obstructive pulmonary disease.