Skip Navigation LinksHome > September 2013 - Volume 24 - Issue 5 > DNA Methylation as a Long-term Biomarker of Exposure to Toba...
Epidemiology:
doi: 10.1097/EDE.0b013e31829d5cb3
Smoking

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

Shenker, Natalie S.a; Ueland, Per Magneb; Polidoro, Silviac; van Veldhoven, Karind; Ricceri, Fulvioc; Brown, Roberta; Flanagan, James M.a; Vineis, Paoloc,d

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Abstract

Background: Most biomarkers of exposure tend to have short half-lives. This includes cotinine, 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 biomarkers for other exposures that are also difficult to quantify in epidemiological studies.

© 2013 by Lippincott Williams & Wilkins, Inc

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