Nicotinic Acetylcholine Receptor Polymorphism, Smoking Behavior, and Tobacco-Related Cancer and Lung and Cardiovascular Diseases: A Cohort Study

Purpose We examined the associations between the nicotinic acetylcholine receptor polymorphism (rs1051730) on chromosome 15q25 marking the gene cluster CHRNA3-CHRNB4-CHRNA5, smoking behavior, and tobacco-related cancer and lung and cardiovascular diseases in the general population. Methods Ten thousand three hundred thirty participants from the Copenhagen City Heart Study were genotyped and observed prospectively with up to 18 years of 100% complete follow-up. Smoking behavior was measured at baseline. End points were lung cancer, bladder cancer, chronic obstructive pulmonary disease, ischemic heart disease, and ischemic stroke. Results Multifactorially adjusted and genotype-adjusted subhazard ratios for a cumulative tobacco consumption above 40 pack-years versus 0 pack-years were 32.5 (95% CI, 12.0 to 87.7) for lung cancer, 2.2 (95% CI, 1.1 to 4.5) for bladder cancer, 9.4 (95% CI, 6.9 to 12.7) for chronic obstructive pulmonary disease, 1.5 (95% CI, 1.3 to 1.8) for ischemic heart disease, and 1.1 (95% CI,...