title: Nicotinic acetylcholine receptor polymorphism, smoking behavior, and tobacco-related cancer and lung and cardiovascular diseases: a cohort study.
abstract: OBJECTIVE
  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, 0.8 to 1.4) for ischemic stroke. Among smoking noncarriers and homozygotes, daily tobacco consumption was 16 and 18 g/d (P < .001), cumulative tobacco consumption was 28 and 31 pack-years (P = .003), and smoking inhalation was 71.9% and 78.1% (P < .001), respectively. Multifactorially adjusted and smoking behavior-adjusted subhazard ratios for homozygotes versus noncarriers were 1.6 (95% CI, 1.1 to 2.2) for lung cancer, 1.7 (95% CI, 1.0 to 3.0) for bladder cancer, 1.3 (95% CI, 1.1 to 1.6) for chronic obstructive pulmonary disease, 0.9 (95% CI, 0.7 to 1.0) for ischemic heart disease, and 1.1 (95% CI, 0.8 to 1.4) for ischemic stroke.
  
  
  CONCLUSIONS
  Although smoking is associated with major tobacco-related diseases in the general population, the nicotinic acetylcholine receptor polymorphism is associated with additional increased risk of lung cancer, bladder cancer, and chronic obstructive pulmonary disease after adjustment for smoking.
authors.affiliation: Herlev Hospital, Copenhagen University Hospital, Copenhagen, Denmark.
authors.forename: Diljit
authors.initials: D
authors.lastname: Kaur-Knudsen
authors.forename: Stig E
authors.initials: SE
authors.lastname: Bojesen
authors.forename: Anne
authors.initials: A
authors.lastname: Tybjærg-Hansen
authors.forename: Børge G
authors.initials: BG
authors.lastname: Nordestgaard
mesh_terms: D000368:Aged; D002545:Brain Ischemia / Q000209:etiology / Q000235:genetics; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000209:etiology* / Q000235:genetics; D016009:Chi-Square Distribution; D003718:Denmark / Q000453:epidemiology; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D015994:Incidence; D008175:Lung Neoplasms / Q000453:epidemiology / Q000209:etiology* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000209:etiology / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D016016:Proportional Hazards Models; D011446:Prospective Studies; D029424:Pulmonary Disease, Chronic Obstructive / Q000453:epidemiology / Q000209:etiology* / Q000235:genetics; D011978:Receptors, Nicotinic / Q000235:genetics*; D018570:Risk Assessment; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects*; D020521:Stroke / Q000209:etiology / Q000235:genetics; D013997:Time Factors; D001749:Urinary Bladder Neoplasms / Q000453:epidemiology / Q000209:etiology* / Q000235:genetics
chemical_list: D009419:Nerve Tissue Proteins; D011978:Receptors, Nicotinic; C447158:CHRNA5 protein, human; C447159:CHRNB4 protein, human