| Smokers with the CHRNA lung cancer-associated variants are exposed to higher levels of nicotine equivalents and a carcinogenic tobacco-specific nitrosamine. | |
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MedLine Citation:
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PMID: 19010884 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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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:
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Type: Journal Article; Research Support, N.I.H., Extramural |
Journal Detail:
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Title: Cancer research Volume: 68 ISSN: 1538-7445 ISO Abbreviation: Cancer Res. Publication Date: 2008 Nov |
Date Detail:
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Created Date: 2008-11-17 Completed Date: 2008-12-10 Revised Date: 2013-01-10 |
Medline Journal Info:
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Nlm Unique ID: 2984705R Medline TA: Cancer Res Country: United States |
Other Details:
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Languages: eng Pagination: 9137-40 Citation Subset: IM |
Affiliation:
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Cancer Research Center of Hawaii, University of Hawaii, Honolulu, Hawaii 96813, USA. oic@crch.hawaii.edu |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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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:
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P50 DA013333/DA/NIDA NIH HHS; P50 DA013333-05/DA/NIDA NIH HHS; P50 DA13333/DA/NIDA NIH HHS; R01 CA085997-05/CA/NCI NIH HHS; R01 CA85997/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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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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