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Lung cancer gene associated with COPD: triple whammy or possible confounding effect?

¹ Dept of Medicine, University of Auckland, ² Synergenz Biosciences Ltd, Auckland, and ³ Dept of Medicine, University of Otago, Christchurch, New Zealand.

CORRESPONDENCE: R. P. Young, Dept of Medicine, Auckland Hospital, Private Bag 92019, Auckland, New Zealand. Fax: 64 96236456. E-mail: roberty{at}adhb.govt.nz

Keywords: Association study, chronic obstructive pulmonary disease, confounding, lung cancer, nicotinic acetylcholine receptor, polymorphism

Received: June 19, 2008
Accepted August 18, 2008

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 5 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 5 subunit nicotinic acetylcholine receptor single nucleotide polymorphism and lung cancer may, in part, be confounded by chronic obstructive pulmonary disease.