DNA methylation differentiates smoking from vaping and non-combustible tobacco use

Andersen, Allan M.; Reimer, Rachel A.; Dawes, Kelsey; Becker, Ashley; Hutchens, Natasha; Miller, Sanford A.; Dogan, Meesha; Hundley, Brandon; Mills, James A.; Long, Jeffrey D.; Philibert, Robert A.

doi:10.1080/15592294.2021.1890875

Cited by 20 publications

(16 citation statements)

References 50 publications

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Section: Methodsmentioning

confidence: 99%

“…The data for these analyses are derived from subjects included in four previously published studies of smoking or alcohol use 26 – 29 . In each of these studies, methylation status at cg05575921 status in WB or saliva DNA was determined using MSdPCR and the smoking status of each non-smoking control was verified using serum cotinine assessments and carbon monoxide assessments as previously described 26 , 29 . All procedures were performed in accordance with the Declaration of Helsinki with the individual institutional approvals noted separately for each cohort being noted in the supplementary methods section with each subject providing written informed consent.…”

Section: Methodsmentioning

confidence: 99%

“…The Smoke Free World (SFW) cohort was collected as part of a project to understand whether DNA methylation could differentiate those who use combustible forms of tobacco from those who use other nicotine containing products 29 . After providing informed consent, adult subjects were administered a 320 item REDCap® interview that assessed nicotine product use history, then phlebotomized and saliva sampled to provide biomaterials for the current study 29 , 32 . Only the data from the smoking subjects and the lifetime non-smoking controls were included in this study.…”

Section: Methodsmentioning

confidence: 99%

“…Over the past 3 years, we have used this assay to assess cg05575921 methylation in the DNA prepared from the whole blood (WB) of four populations of subjects who were clinically characterized for smoking status and with the non-use status of all control subjects being verified using both serum cotinine and exhaled carbon monoxide assessments 26 – 29 . In an attempt to provide a more robust understanding of the relationship of WB cg05575921 methylation to smoking status, we now jointly analyze those results.…”

Section: Introductionmentioning

confidence: 99%

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The relationship of smoking to cg05575921 methylation in blood and saliva DNA samples from several studies

Dawes

Andersen

Reimer

et al. 2021

Sci Rep

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Numerous studies have shown that cg05575921 methylation decreases in response to smoking. However, secondary to methodological issues, the magnitude and dose dependency of that response is as of yet unclear. This lack of certainty is a barrier to the use of DNA methylation clinically to assess and monitor smoking status. To better define this relationship, we conducted a joint analysis of methylation sensitive PCR digital (MSdPCR) assessments of cg05575921 methylation in whole blood and/or saliva DNA to smoking using samples from 421 smokers and 423 biochemically confirmed non-smokers from 4 previously published studies. We found that cg05575921 methylation manifested a curvilinear dose dependent decrease in response to increasing cigarette consumption. In whole blood DNA, the Receiver Operating Characteristic (ROC) Area Under the Curve (AUC) of cg05575921 methylation for predicting daily smoking status was 0.98. In saliva DNA, the gross AUC was 0.91 with correction for cellular heterogeneity improving the AUC to 0.94. Methylation status was significantly associated with the Fagerstrom Test for Nicotine Dependence score, but with significant sampling heterogeneity. We conclude that MSdPCR assessments of cg05575921 methylation are a potentially powerful, clinically implementable tool for the assessment and management of smoking.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

The relationship of smoking to cg05575921 methylation in blood and saliva DNA samples from several studies

Dawes

Andersen

Reimer

et al. 2021

Sci Rep

Self Cite

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“…However, when considering these results, it is important to realize that, just as not all cases of CHD are equally severe, not all smokers consume the same number of cigarettes. Fortunately, the use of cg05575921 as a metric for change in smoking intensity permits the stable objective measurement of smoking intensity [17,19]. Recently, we have shown that changes in cg05575921 methylation in response to smoking cessation are also dosedependent [16].…”

Section: Resultsmentioning

confidence: 99%

The Reversion of DNA Methylation at Coronary Heart Disease Risk Loci in Response to Prevention Therapy

et al. 2021

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Coronary heart disease (CHD) is preventable, but the methods for assessing risk and monitoring response rely on imprecise lipid-based assessments. Recently, we have shown that an integrated genetic–epigenetic test that includes three methylation-sensitive digital PCR assays predicts 3-year risk for incident CHD better than lipid-based methods. However, whether methylation sites change in response to therapies that alter CHD risk is not known. Therefore, we assessed methylation at these three incident CHD-related sites in DNA from 39 subjects before and after three months of biochemically verified smoking cessation, then analyzed the relationship between change in methylation at each of the sites to the change in smoking intensity as assessed by cg05575921 methylation. We found that, in those who quit smoking, methylation change at one CHD risk marker (cg00300879) was significantly associated with change in cg05575921 methylation (p < 0.04). We conclude that changes in incident CHD-related methylation occur within three months of cessation of smoking, a major risk factor for CHD. This suggests that the effectiveness of treatment of other CHD risk factors, such as high cholesterol, may be similarly quantifiable using epigenetic approaches. Further studies to determine the relationship of changes of methylation status in response to treatment of other CHD risk factors are indicated.

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Lifetime marijuana use and epigenetic age acceleration: A 17-year prospective examination

Allen¹,

Danoff²,

Costello³

et al. 2022

Drug and Alcohol Dependence

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DNA methylation differentiates smoking from vaping and non-combustible tobacco use

Cited by 20 publications

References 50 publications

The relationship of smoking to cg05575921 methylation in blood and saliva DNA samples from several studies

The relationship of smoking to cg05575921 methylation in blood and saliva DNA samples from several studies

The Reversion of DNA Methylation at Coronary Heart Disease Risk Loci in Response to Prevention Therapy

Lifetime marijuana use and epigenetic age acceleration: A 17-year prospective examination

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