Epigenetic Signatures of Cigarette Smoking

Abstract

Background DNA methylation leaves a long-term signature of smoking exposure and is one potential mechanism by which tobacco exposure predisposes to adverse health outcomes, such as cancers, osteoporosis, lung, and cardiovascular disorders. Methods and Results To comprehensively determine the association between cigarette smoking and DNA methylation, we conducted a meta-analysis of genome-wide DNA methylation assessed using the Illumina BeadChip 450K array on 15,907 blood derived DNA samples from participants in 16 cohorts (including 2,433 current, 6,518 former, and 6,956 never smokers). Comparing current versus never smokers, 2,623 CpG sites (CpGs), annotated to 1,405 genes, were statistically significantly differentially methylated at Bonferroni threshold of p<1×10−7 (18,760 CpGs at False Discovery Rate (FDR)<0.05). Genes annotated to these CpGs were enriched for associations with several smoking-related traits in genome-wide studies including pulmonary function, cancers, inflammatory diseases and heart disease. Comparing former versus never smokers, 185 of the CpGs that differed between current and never smokers were significant p<1×10−7 (2,623 CpGs at FDR<0.05), indicating a pattern of persistent altered methylation, with attenuation, after smoking cessation. Transcriptomic integration identified effects on gene expression at many differentially methylated CpGs. Conclusions Cigarette smoking has a broad impact on genome-wide methylation that, at many loci, persists many years after smoking cessation. Many of the differentially methylated genes were novel genes with respect to biologic effects of smoking, and might represent therapeutic targets for prevention or treatment of tobacco-related diseases. Methylation at these sites could also serve as sensitive and stable biomarkers of lifetime exposure to tobacco smoke.

The dynamics of smoking-related disturbed methylation: a two time-point study of methylation change in smokers, non-smokers and former smokers

“…All regions corresponding to the CpG sites significant in this analysis, and all CpG sites themselves, have previously been identified as being associated with smoking [8,12,[33][34][35][36], and discussed with regard to their biological implications in a number of publications, in particular 2q37.1 [8,13,37], AHRR [7,38,39], GFI1 [40], MYO1G [41] and F2RL3 [7,42]. Further, most of these loci have been identified as associated with conditions or diseases also related to smoking.…”

“…The link between smoking and methylation is receiving growing attention [7], with numerous recent crosssectional studies revealing epigenome-wide associations [8][9][10][11][12]. The most recent, comprehensive analyses include a systematic review of 17 studies [13], and a meta-analysis of 16 cohorts [12], the latter revealing 2623 CpGs sites significantly associated with smoking behavior at a strict multiple testing threshold.…”

“…The most recent, comprehensive analyses include a systematic review of 17 studies [13], and a meta-analysis of 16 cohorts [12], the latter revealing 2623 CpGs sites significantly associated with smoking behavior at a strict multiple testing threshold. However, longitudinal studies -here defined as those examining methylation and smoking habits in individuals at two or more time-points -are scarce.…”

Asbestos‐associated genome‐wide DNA methylation changes in lung cancer

“…These included DVMCs in CARD11 (cg15658543), SMYD3 (cg22019569), CPE (cg26812418) and AHRR (cg08491376, cg00401753) and as many as 87% (7/8) of the smoking-associated genes with DMP in our study. 23,43,44 However, the smoking-related mean methylation changes discovered in our DMR analysis were minor, possibly because we compared two groups of smokers, having either lower ( 36) or higher pack-years (>36). Interestingly though, we detected cg13751927 in F2RL3 as a smoking-linked significant DVMC in T and N. The cg13751927 located in a CGI in F2RL3 at a range of only 299 nucleotides from cg03636183; lowered methylation of cg03636183 has been convincingly associated with smoking in peripheral blood cells.…”

Perfil dos Trabalhadores Motoristas e Fatores para Doenças Cardiovasculares

“…Porém o estudo não perde sua importância para os profissionais envolvidos, pesquisadores, bem como para a comunidade cientifica, pois a grande maioria das empresas da região oeste de Santa Catarina tem pequeno porte até 50 funcionários e este estudo deu a possibilidade de um olhar mais atento de seus dirigentes, e da rede de saúde do trabalhador do município de Chapecó SC. organismo 21,22 . A cessação do fumo reduz, substancialmente, o risco de desenvolver agravos à saúde, porém exfumantes sempre terão maior probabilidade de ter doenças cardiovasculares e câncer, do que indivíduos que nunca fumaram 23 .…”