Investigating the DNA methylation profile of e-cigarette use

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Little 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.

Among 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).

The 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.
Original languageEnglish
Article number183
Number of pages13
JournalClinical Epigenetics
Issue number1
Early online date28 Sept 2021
Publication statusPublished - Dec 2021

Bibliographical note

Funding Information:
This work was supported by a Cancer Research UK Population Research Committee project grant (C57854/A22171). Further support was provided by the UK Medical Research Council (MC_UU_00011/5 and MC_UU_00011/7), which funds a Unit at the University of Bristol where R.C.R., C.S.R., J.K., C.P., G.S., M.S., C.L.R and M.M. work, and the CRUK-funded Integrative Cancer Epidemiology Programme (C18281/A19169). R.C.R is a de Pass Vice Chancellor’s Research Fellow at the University of Bristol. C.S.R’s time is supported by the National Institute for Health Research Applied Research Collaboration West (NIHR ARC West) at University Hospitals Bristol NHS Foundation Trust. C.P. is supported by a Wellcome Trust PhD studentship in Molecular, Genetic and Lifecourse Epidemiology (108902/B/15/Z). The UK Medical Research Council and Wellcome (Grant ref: 102215/2/13/2) and the University of Bristol provide core support for ALSPAC. This publication is the work of the authors who will serve as guarantors for the contents of this paper. A comprehensive list of grants funding is available on the ALSPAC website ( ).

Publisher Copyright:
© 2021, The Author(s).

Structured keywords

  • ICEP


  • e-cigarettes
  • DNA methylation
  • smoking
  • SEE-Cigs


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