Investigating the DNA methylation profile of e-cigarette use

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

doi:10.1186/s13148-021-01174-7

Investigating the DNA methylation profile of e-cigarette use

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

University of Bristol
University Hospitals Bristol NHS Foundation Trust
University of Oxford
University of Liverpool

Research output: Contribution to journal › Article › peer-review

23 Citations (SciVal)

Abstract

Background: 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.

Results: 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).

Conclusions: 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 language	English
Article number	183
Journal	CLINICAL EPIGENETICS
Volume	13
Issue number	1
Early online date	28 Sept 2021
DOIs	https://doi.org/10.1186/s13148-021-01174-7
Publication status	Published - 31 Dec 2021

Data Availability Statement

The underlying methylation and phenotypic data used in this study cannot be made publicly available since the data contain information that could compromise participant consent and confidentiality. Full summary data from the epigenome-wide association studies conducted as part of the main analysis have been uploaded to the EWAS Catalog (http://www.ewascatalog.org/).

Acknowledgements

SEE-Cigs—We are extremely grateful to all the participants who took part in this study. ALSPAC—We are extremely grateful to all the families who took part in this study, the midwives for their help in recruiting them, and the whole ALSPAC team, which includes interviewers, computer and laboratory technicians, clerical workers, research scientists, volunteers, managers, receptionists and nurses.

Funding

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 (http://www.bristol.ac.uk/alspac/external/documents/grant-acknowledgements.pdf).

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

ALSPAC
DNA methylation
e-cigarettes
SEE-Cigs
Smoking

ASJC Scopus subject areas

Molecular Biology
Genetics
Developmental Biology
Genetics(clinical)

Access to Document

10.1186/s13148-021-01174-7Licence: CC BY

Cite this

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title = "Investigating the DNA methylation profile of e-cigarette use",

abstract = "Background: 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. Results: 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 {\texttimes} 10{\textendash}5 and none at p < 5.91 {\texttimes} 10{\textendash}8. 13 CpGs were associated with smoking at p < 1 {\texttimes} 10{\textendash}5 and one at p < 5.91 {\texttimes} 10{\textendash}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{\textendash}0.69) and externally (AUC 0.57, 0.36{\textendash}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{\textendash}0.76 versus AUC 0.73, 0.61{\textendash}0.85). Conclusions: 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.",

keywords = "ALSPAC, DNA methylation, e-cigarettes, SEE-Cigs, Smoking",

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AU - Richmond, Rebecca C.

AU - Sillero-Rejon, Carlos

AU - Khouja, Jasmine N.

AU - Prince, Claire

AU - Board, Alexander

AU - Sharp, Gemma

AU - Suderman, Matthew

AU - Relton, Caroline L.

AU - Munafò, Marcus

AU - Gage, Suzanne H.

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N2 - Background: 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. Results: 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). Conclusions: 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.

AB - Background: 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. Results: 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). Conclusions: 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.

KW - ALSPAC

KW - DNA methylation

KW - e-cigarettes

KW - SEE-Cigs

KW - Smoking

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DO - 10.1186/s13148-021-01174-7

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Investigating the DNA methylation profile of e-cigarette use

Abstract

Data Availability Statement

Acknowledgements

Funding

UN SDGs

Keywords

ASJC Scopus subject areas

Access to Document

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