Nicotinic acetylcholine receptor polymorphism, smoking history, and tobacco-related cancer in the general population.

1530 Background: Smokers often develop lung and bladder cancer; however, not all smokers develop these diseases. We examined whether the nicotinic acetylcholine receptor gene (CHRNA3) rs1051730 polymorphism can identify smokers in the general population at genetically high risk of tobacco-related cancer, that is, at higher risk than that explained by detailed smoking history alone. Methods: We genotyped 10,322 participants from the Danish general population, the Copenhagen City Heart Study. Detailed smoking history was obtained and validated at baseline. End-points during the following 18 years were lung and bladder cancer from the Danish cancer registry. Follow-up was 100% complete. Results: Among the 7831 ever smokers, CHRNA3 non-carriers (44%) and homozygotes (11%) had daily tobacco consumption of 16 and 18 g/day (Wilcoxon: p = 0.000004), cumulative tobacco consumption of 28 to 31 packyears (p = 0.001), and smoking inhalation of 72% and 78% (chi- square: p = 0.0002). As expected increasing baseline pac...