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Investigating the DNA methylation profile of e-cigarette use

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

Posted 31 Jan 2021
medRxiv DOI: 10.1101/2021.01.28.21250699

Rationale and objectives 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. Methods Among 117 smokers, 117 non-smokers and 116 non-smoking vapers, we evaluated associations between e-cigarette use and epigenome-wide methylation from saliva. We tested associations between e-cigarette use and methylation scores known to predict smoking and smoking-related disease. We assessed the ability of a methylation score for predicting e-cigarette use and for discriminating lung cancer. Measurements and Main Results 7 CpGs were identified in relation to e-cigarette use at p<1x10-5 and none at p<5.91x10-8. 13 CpGs were associated with smoking at p<1x10-5 and one at p<5.91x10-8. 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. 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.

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