Investigating the DNA methylation profile of e-cigarette use

Rebecca C Richmond,Jasmine N Khouja,Claire Prince,Carlos Sillero-Rejon,Caroline L Relton,Matthew Suderman,Gemma Sharp,Marcus Munafò,Suzanne H Gage,Alexander Board

doi:10.1186/s13148-021-01174-7

Abstract

BackgroundLittle evidence exists on the health effects of e-cigarette use. DNA methylation may serve as a biomarker for exposure and could be predictive of future health risk. We aimed to investigate the DNA methylation profile of e-cigarette use.ResultsAmong 117 smokers, 117 non-smokers and 116 non-smoking vapers, we evaluated associations between e-cigarette use and epigenome-wide methylation from saliva. DNA methylation at 7 cytosine-phosphate-guanine sites (CpGs) was associated with e-cigarette use at p < 1 × 10–5 and none at p < 5.91 × 10–8. 13 CpGs were associated with smoking at p < 1 × 10–5 and one at p < 5.91 × 10–8. CpGs associated with e-cigarette use were largely distinct from those associated with smoking. There was strong enrichment of known smoking-related CpGs in the smokers but not the vapers. We also tested associations between e-cigarette use and methylation scores known to predict smoking and biological ageing. Methylation scores for smoking and biological ageing were similar between vapers and non-smokers. Higher levels of all smoking scores and a biological ageing score (GrimAge) were observed in smokers. A methylation score for e-cigarette use showed poor prediction internally (AUC 0.55, 0.41–0.69) and externally (AUC 0.57, 0.36–0.74) compared with a smoking score (AUCs 0.80) and was less able to discriminate lung squamous cell carcinoma from adjacent normal tissue (AUC 0.64, 0.52–0.76 versus AUC 0.73, 0.61–0.85).ConclusionsThe DNA methylation profile for e-cigarette use is largely distinct from that of cigarette smoking, did not replicate in independent samples, and was unable to discriminate lung cancer from normal tissue. The extent to which methylation related to long-term e-cigarette use translates into chronic effects requires further investigation.

Highlights

Electronic cigarettes (e-cigarettes) have the potential to reduce smoking-related harm
For the cytosine-phosphate-guanine sites (CpGs) sites identified in the Epigenome‐wide association study (EWAS) of vapers versus non-smokers, and smokers versus non-smokers, we investigated whether there was evidence of a dose response in methylation levels based on the length of exposure history (6 months–1 year vs > 1 year for e-cigarette use, 6 months–5 years vs > 5 years for smoking)
We investigated whether the methylation scores for e-cigarette use was able to discriminate tumour from normal tissue in lung to the same extent as the methylation score for smoking, using data from publicly available methylation data in The Cancer Genome Atlas (TCGA) [41]

Summary

Introduction

Electronic cigarettes (e-cigarettes) have the potential to reduce smoking-related harm. Little evidence currently exists on long-term effects, their lack of tar and very low levels of other dangerous substances [1] suggest they are considerably less harmful than cigarettes [2]. They have been shown to be an efficacious [3] and cost-effective [4] smoking cessation aid. Pronounced differences in methylation have been found between cigarette smokers and non-smokers [10] These have been replicated in different populations [11, 12] and tissues [13], shown to persist for several years post-cessation [10], are able distinguish tumour from normal samples [14], and are predictive of disease and mortality [15, 16]. We aimed to investigate the DNA methylation profile of e-cigarette use

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