Tobacco smoking-associated genome-wide DNA methylation changes in the EPIC study.
Ambatipudi S., Cuenin C., Hernandez-Vargas H., Ghantous A., Le Calvez-Kelm F., Kaaks R., Barrdahl M., Boeing H., Aleksandrova K., Trichopoulou A., Lagiou P., Naska A., Palli D., Krogh V., Polidoro S., Tumino R., Panico S., Bueno-de-Mesquita B., Peeters PH., Quirós JR., Navarro C., Ardanaz E., Dorronsoro M., Key T., Vineis P., Murphy N., Riboli E., Romieu I., Herceg Z.
AIM: Epigenetic changes may occur in response to environmental stressors, and an altered epigenome pattern may represent a stable signature of environmental exposure. MATERIALS & METHODS: Here, we examined the potential of DNA methylation changes in 910 prediagnostic peripheral blood samples as a marker of exposure to tobacco smoke in a large multinational cohort. RESULTS: We identified 748 CpG sites that were differentially methylated between smokers and nonsmokers, among which we identified novel regionally clustered CpGs associated with active smoking. Importantly, we found a marked reversibility of methylation changes after smoking cessation, although specific genes remained differentially methylated up to 22 years after cessation. CONCLUSION: Our study has comprehensively cataloged the smoking-associated DNA methylation alterations and showed that these alterations are reversible after smoking cessation.