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Nicotinic acetylcholine receptor polymorphism, smoking behavior, and tobacco-related cancer and lung and cardiovascular diseases: a cohort study.
- Source :
-
Journal of clinical oncology : official journal of the American Society of Clinical Oncology [J Clin Oncol] 2011 Jul 20; Vol. 29 (21), pp. 2875-82. Date of Electronic Publication: 2011 Jun 06. - Publication Year :
- 2011
-
Abstract
- 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.<br />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.<br />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.<br />Conclusion: 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.
- Subjects :
- Aged
Brain Ischemia etiology
Brain Ischemia genetics
Cardiovascular Diseases epidemiology
Cardiovascular Diseases genetics
Chi-Square Distribution
Denmark epidemiology
Female
Genetic Predisposition to Disease
Humans
Incidence
Lung Neoplasms epidemiology
Lung Neoplasms genetics
Male
Middle Aged
Myocardial Ischemia etiology
Myocardial Ischemia genetics
Nerve Tissue Proteins genetics
Proportional Hazards Models
Prospective Studies
Pulmonary Disease, Chronic Obstructive epidemiology
Pulmonary Disease, Chronic Obstructive genetics
Risk Assessment
Risk Factors
Stroke etiology
Stroke genetics
Time Factors
Urinary Bladder Neoplasms epidemiology
Urinary Bladder Neoplasms genetics
Cardiovascular Diseases etiology
Lung Neoplasms etiology
Polymorphism, Single Nucleotide
Pulmonary Disease, Chronic Obstructive etiology
Receptors, Nicotinic genetics
Smoking adverse effects
Urinary Bladder Neoplasms etiology
Subjects
Details
- Language :
- English
- ISSN :
- 1527-7755
- Volume :
- 29
- Issue :
- 21
- Database :
- MEDLINE
- Journal :
- Journal of clinical oncology : official journal of the American Society of Clinical Oncology
- Publication Type :
- Academic Journal
- Accession number :
- 21646606
- Full Text :
- https://doi.org/10.1200/JCO.2010.32.9870