Cigarette Smoking and E-cigarette Use Induce Shared DNA Methylation Changes Linked to Carcinogenesis

Area of Science:

• Epigenetics and Molecular Biology
• Cancer Research
• Public Health

Background:

• Tobacco use is a significant risk factor for cancer, inducing epigenetic changes linked to long-term risk.
• Electronic cigarettes (e-cigarettes) are promoted for harm reduction, but their molecular and health impacts require further investigation.
• Understanding cell- and tissue-specific epigenetic effects of smoking and vaping is crucial for assessing health risks.

Purpose of the Study:

• To investigate the cell- and tissue-specific epigenetic effects of tobacco and e-cigarette use on DNA methylation.
• To identify DNA methylation loci associated with smoking and their potential role in carcinogenesis.
• To compare the epigenetic impacts of traditional smoking versus e-cigarette use.

Main Methods:

• Applied computational deconvolution to analyze DNA methylation (DNAme) in over 3,500 buccal/saliva, cervical, and blood samples.
• Examined epithelial and immune cells from directly and indirectly exposed sites.
• Identified 535 smoking-related DNA methylation loci (CpG sites) and analyzed their functional clustering and association with cancer.

Main Results:

• Identified 535 smoking-related DNAme loci, clustering into functional groups like detoxification and growth signaling.
• Hypermethylation in buccal epithelial cells of smokers, associated with NOTCH1/RUNX3/growth factor receptor signaling, was linked to cancer tissue and predicted lung cancer development years prior.
• Alarmingly, these cancer-associated CpG sites were also hypermethylated in e-cigarette users, even with limited smoking history.

Conclusions:

• Both cigarette and e-cigarette use induce cell- and exposure-specific epigenetic changes that are predictive of carcinogenesis.
• Specific DNA methylation patterns in buccal cells associated with smoking can predict future lung cancer risk.
• The findings suggest caution regarding the broad recommendation of e-cigarettes as smoking cessation aids due to shared epigenetic risks.