TY - JOUR

T1 - Changing Smoking Behavior and Epigenetics

T2 - A Longitudinal Study of 4,432 Individuals From the General Population

AU - Skov-Jeppesen, Sune Moeller

AU - Kobylecki, Camilla Jannie

AU - Jacobsen, Katja Kemp

AU - Bojesen, Stig Egil

N1 - Publisher Copyright: © 2023 The Author(s)

PY - 2023

Y1 - 2023

N2 - 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: participants 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.

AB - 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: participants 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.

KW - aryl hydrocarbon receptor repressor

KW - DNA methylation

KW - longitudinal study

KW - lung cancer

KW - smoking

U2 - 10.1016/j.chest.2022.12.036

DO - 10.1016/j.chest.2022.12.036

M3 - Journal article

C2 - 36621758

AN - SCOPUS:85159892058

VL - 163

SP - 1565

EP - 1575

JO - Chest

JF - Chest

SN - 0012-3692

IS - 6

ER -