Document Detail


Smokers with the CHRNA lung cancer-associated variants are exposed to higher levels of nicotine equivalents and a carcinogenic tobacco-specific nitrosamine.
MedLine Citation:
PMID:  19010884     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
A locus at 15q24/15q25.1, which includes the nicotinic acetylcholine receptor A subunits 3 and 5 (CHRNA3 and CHRNA5) genes, has recently been associated with lung cancer risk, self-reported number of cigarettes smoked per day, and a nicotine dependence scale. It is not clear whether the association with lung cancer is direct or mediated through differences in smoking behavior. We used urinary biomarkers to test whether two linked lung cancer risk variants in CHRNA3 (rs1051730) and CHRNA5 (rs16969968) are associated with intensity of smoking and exposure to a tobacco-specific carcinogenic nitrosamine per cigarette dose. We studied 819 smokers and found that carriers of these variants extract a greater amount of nicotine (P = 0.003) and are exposed to a higher internal dose of 4-(methylnitrosamino)-I-(3-pyridyl)-1-butanone (P = 0.03) per cigarette than noncarriers. Thus, smokers who carry the CHRNA3 and CHRNA5 variants are expected to be at increased risk for lung cancer compared with smokers who do not carry these alleles even if they smoked the same number of cigarettes. Number of cigarettes per day, even if it could be accurately assessed, is not an adequate measure of smoking dose.
Authors:
Loïc Le Marchand; Kiersten S Derby; Sharon E Murphy; Stephen S Hecht; Dorothy Hatsukami; Steven G Carmella; Maarit Tiirikainen; Hansong Wang
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Cancer research     Volume:  68     ISSN:  1538-7445     ISO Abbreviation:  Cancer Res.     Publication Date:  2008 Nov 
Date Detail:
Created Date:  2008-11-17     Completed Date:  2008-12-10     Revised Date:  2014-09-12    
Medline Journal Info:
Nlm Unique ID:  2984705R     Medline TA:  Cancer Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  9137-40     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Adult
Aged
Female
Humans
Lung Neoplasms / etiology*
Male
Middle Aged
Nerve Tissue Proteins / genetics*
Nicotine / toxicity*
Nitrosamines / toxicity*
Polymorphism, Single Nucleotide
Pyridines / toxicity*
Receptors, Nicotinic / genetics*
Smoking / adverse effects*
Grant Support
ID/Acronym/Agency:
P50 DA013333/DA/NIDA NIH HHS; P50 DA013333-05/DA/NIDA NIH HHS; P50 DA13333/DA/NIDA NIH HHS; R01 CA085997/CA/NCI NIH HHS; R01 CA085997-05/CA/NCI NIH HHS; R01 CA85997/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/4-(methylnitrosamino)-1-(3-pyridyl)-1-butan-1-ol; 0/CHRNA5 protein, human; 0/Nerve Tissue Proteins; 0/Nitrosamines; 0/Pyridines; 0/Receptors, Nicotinic; 0/nicotinic receptor subunit alpha3; 54-11-5/Nicotine; 64091-91-4/4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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