Reversion of AHRR Demethylation Is a Quantitative Biomarker of Smoking Cessation
Robert A. Philibert,Nancy Hollenbeck,Eleanor Andersen,Shyheme McElroy,Scott L. Wilson,Kyra Vercande,Steven R. H. Beach,Terry Osborn,Meg Gerrard,Frederick X. Gibbons,Kai Wang +10 more
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TLDR
It is concluded that AHRR methylation status is a quantifiable biomarker for progress in smoking cessation that could have substantial impact on both smoking cessation treatment and research.Abstract:
Smoking is the largest preventable cause of morbidity and mortality in the world. Although there are effective pharmacologic and behavioral treatments for smoking cessation, our inability to objectively quantify smokers’ progress in decreasing smoking has been a barrier to both clinical and research efforts. In prior work, we and others have shown that DNA methylation at cg05575921, a CpG residue in the aryl hydrocarbon receptor repressor (AHRR), can be used to determine smoking status and infer cigarette consumption history. In this study, we serially assessed self-report and existing objective markers of cigarette consumption in 35 subjects undergoing smoking cessation therapy, then quantified DNA methylation at cg05575921 at study entry and three subsequent time points. Five subjects who reported serum cotinine and exhaled carbon monoxide verified smoking abstinence for the three months prior to study exit averaged a 5.9% increase in DNA methylation at cg05575921 (p<0.004) over the six month study. Although the other 30 subjects did not achieve smoking cessation at the six-month time point, their self-reported reduction of cigarette consumption (mean = 6 cigarettes per day) was associated with a 2.8% increase DNA methylation at cg05575921 (p<0.05). Finally, a survey of subjects as they exited the study demonstrated strong support for the clinical use of epigenetic biomarkers. We conclude that AHRR methylation status is a quantifiable biomarker for progress in smoking cessation that could have substantial impact on both smoking cessation treatment and research.read more
Citations
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Journal ArticleDOI
AHRR (cg05575921) hypomethylation marks smoking behaviour, morbidity and mortality
Stig E. Bojesen,Stig E. Bojesen,Nicholas J. Timpson,Caroline L Relton,George Davey Smith,Børge G. Nordestgaard,Børge G. Nordestgaard +6 more
TL;DR: AHRR (cg05575921) hypomethylation, a marker of smoking behaviour, provides potentially clinical relevant predictions of future smoking-related morbidity and mortality.
Journal ArticleDOI
The dynamics of smoking-related disturbed methylation: a two time-point study of methylation change in smokers, non-smokers and former smokers.
Rory P. Wilson,Simone Wahl,Liliane Pfeiffer,Cavin K. Ward-Caviness,Sonja Kunze,Anja Kretschmer,Eva Reischl,Annette Peters,Christian Gieger,Melanie Waldenberger +9 more
TL;DR: This study improves the understanding of the dynamic link between cigarette smoking and methylation, revealing the continued fluctuation of methylation levels decades after smoking cessation and demonstrating that continuing smoking can have an array of effects.
Journal ArticleDOI
Epigenetic signatures of starting and stopping smoking.
Daniel L. McCartney,Anna J. Stevenson,Robert F. Hillary,Rosie M. Walker,Mairead L. Bermingham,Stewart W. Morris,Toni-Kim Clarke,Archie Campbell,Alison D. Murray,Heather C. Whalley,David J. Porteous,Peter M. Visscher,Andrew M. McIntosh,Kathryn L. Evans,Ian J. Deary,Riccardo E. Marioni +15 more
TL;DR: The findings suggest that smoking–associated DNA methylation changes are a result of prolonged exposure to cigarette smoke, and can be reversed following cessation, and may provide an additional criterion on which to stratify risk.
Journal ArticleDOI
A systematic review of smoking-related epigenetic alterations.
TL;DR: This systematic review lists the epigenetic events/alterations known to occur in response to cigarette smoke exposure and identifies the major genes and miRNAs that are potential targets for translational research in associated pathologies.
Journal ArticleDOI
Establishing a generalized polyepigenetic biomarker for tobacco smoking.
Karen Sugden,Eilis Hannon,Louise Arseneault,Daniel W. Belsky,Jonathan M. Broadbent,David L. Corcoran,Robert J. Hancox,Renate Houts,Terrie E. Moffitt,Richie Poulton,Joseph A. Prinz,W. Murray Thomson,Benjamin Williams,Chloe C. Y. Wong,Jonathan Mill,Avshalom Caspi +15 more
TL;DR: The construction of a polyepigenetic DNA methylation score is described that indexes smoking behavior and that can be utilized for multiple purposes in population health research and introduced as a tool both for discovery and theory-guided research in epigenetic epidemiology.
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