Changing Smoking Behavior and Epigenetics A Longitudinal Study of 4,432 Individuals From the General Population

BACKGROUND: Hypomethylation of the aryl hydrocarbon receptor repressor (AHRR) gene indicates long-term smoking exposure and might therefore be a monitor for smoking -induced disease risk. However, studies of individual longitudinal changes in AHRR methylation are sparse.RESEARCH QUESTION: How does the recovery of AHRR methylation depend on change in smoking behaviors and demographic variables?STUDY DESIGN AND METHODS: This study included 4,432 individuals from the Copenhagen City Heart Study, with baseline and follow-up blood samples and smoking information collected approximately 10 years apart. AHRR methylation at the cg05575921 site was measured in bisulfite-treated leukocyte DNA. Four smoking groups were defined: partici-pants who never smoked (Never-Never), participants who formerly smoked (Former -Former), participants who quit during the study period (Current-Former), and individuals who smoked at both baseline and follow-up (Current-Current). Methylation recovery was defined as the increase in AHRR methylation between baseline and follow-up examination. RESULTS: Methylation recovery was highest among participants who quit, with a median methylation recovery of 5.58% (interquartile range, 1.79; 9.15) vs 1.64% (interquartile range, -1.88; 4.96) in the Current-Current group (P < .0001). In individuals who quit smoking, older age was associated with lower methylation recovery (P < .0001). In participants who quit aged > 65 years, methylation recovery was 5.9% at 5.6 years after quitting; methylation recovery was 8.5% after 2.8 years for participants who quit aged < 55 years.INTERPRETATION: AHRR methylation recovered after individuals quit smoking, and recovery was more pronounced and occurred faster in younger compared with older interim quitters. CHEST 2023; 163(6):1565-1575

Automated summary

This study investigated the relationship between AHRR gene methylation and smoking behaviors and demographic variables. The research found that AHRR gene methylation could recover after quitting smoking, and the recovery was more pronounced and faster in younger individuals.