DNA Methylation as a Long-term Biomarker of Exposure to Tobacco Smoke

Background: Most biomarkers of exposure tend to have short half-lives. This includes continine, a metabolite of nicotine widely used to assess smoke exposure. Cotinine is thus unsuitable as a determinant of past exposure to cigarette smoke. Methods: We used bisulphite pyrosequencing of a set of four...

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Bibliographic Details
Published in:Epidemiology (Cambridge, Mass.) Mass.), 2013-09, Vol.24 (5), p.712-716
Main Authors: Shenker, Natalie S., Ueland, Per Magne, Polidoro, Silvia, van Veldhoven, Karin, Ricceri, Fulvio, Brown, Robert, Flanagan, James M., Vineis, Paolo
Format: Article
Language:English
Subjects:
Biological and medical sciences
Biomarkers - blood
Cotinine - blood
DNA Methylation
Epidemiology
Female
General aspects
Humans
Male
Medical sciences
Miscellaneous
Prospective Studies
Public health. Hygiene
Public health. Hygiene-occupational medicine
Reproducibility of Results
Smoking
Smoking - blood
Smoking - genetics
Surveys and Questionnaires
Time Factors
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Summary:Background: Most biomarkers of exposure tend to have short half-lives. This includes continine, a metabolite of nicotine widely used to assess smoke exposure. Cotinine is thus unsuitable as a determinant of past exposure to cigarette smoke. Methods: We used bisulphite pyrosequencing of a set of four genomic loci (AHRR, 6p21, and two at 2q37) that had differential DNA methylation levels in peripheral blood DNA dependent on tobacco exposure to create a predictive model of smoking status. Results: Combining four gene loci into a single methylation index provided high positive predictive and sensitivity values for predicting former smoking status in both test (n = 81) and validation (n = 180) sample sets. Conclusions: This study provides a direct molecular measure of prior exposure to tobacco that can be performed using the quantitative approach of bisulphite pyrosequencing. Epigenetic changes that are detectable in blood may more generally act as molecular bio-markers for other exposures that are also difficult to quantify in epidemiological studies.
ISSN:1044-3983
1531-5487
DOI:10.1097/ede.0b013e31829d5cb3