Dataset Information

Cigarette smoking behaviors and time since quitting are associated with differential DNA methylation across the human genome.

ABSTRACT: The impact of cigarette smoking can persist for extended periods following smoking cessation and may involve epigenetic reprogramming. Changes in DNA methylation associated with smoking may help to identify molecular pathways that contribute to the latency between exposure and disease onset. Cross-sectional cohort data from subjects in the International COPD Genetics Network (n = 1085) and the Boston Early-Onset COPD study (n = 369) were analyzed as the discovery and replication cohorts, respectively. Genome-wide methylation data on 27 578 CpG sites in 14 475 genes were obtained on DNA from peripheral blood leukocytes using the Illumina HumanMethylation27K Beadchip in both cohorts. We identified 15 sites significantly associated with current smoking, 2 sites associated with cumulative smoke exposure, and, within the subset of former smokers, 3 sites associated with time since quitting cigarettes. Two loci, factor II receptor-like 3 (F2RL3) and G-protein-coupled receptor 15 (GPR15), were significantly associated in all three analyses and were validated by pyrosequencing. These findings (i) identify a novel locus (GPR15) associated with cigarette smoking and (ii) suggest the existence of dynamic, site-specific methylation changes in response to smoking which may contribute to the extended risks associated with cigarette smoking that persist after cessation.

SUBMITTER: Wan ES

PROVIDER: S-EPMC3373248 | biostudies-literature | 2012 Jul

REPOSITORIES: biostudies-literature

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Cigarette smoking behaviors and time since quitting are associated with differential DNA methylation across the human genome.

Wan Emily S ES Qiu Weiliang W Baccarelli Andrea A Carey Vincent J VJ Bacherman Helene H Rennard Stephen I SI Agusti Alvar A Anderson Wayne W Lomas David A DA Demeo Dawn L DL

Human molecular genetics 20120406 13

The impact of cigarette smoking can persist for extended periods following smoking cessation and may involve epigenetic reprogramming. Changes in DNA methylation associated with smoking may help to identify molecular pathways that contribute to the latency between exposure and disease onset. Cross-sectional cohort data from subjects in the International COPD Genetics Network (n = 1085) and the Boston Early-Onset COPD study (n = 369) were analyzed as the discovery and replication cohorts, respect ...[more]

PMID: 22492999

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Project description:Smoking is a risk factor for many human diseases. DNA methylation has been related to smoking, but genome-wide methylation data for smoking in Chinese populations is limited.We aimed to investigate epigenome-wide methylation in relation to smoking in a Chinese population.We measured the methylation levels at > 485,000 CpG sites (CpGs) in DNA from leukocytes using a methylation array and conducted a genome-wide meta-analysis of DNA methylation and smoking in a total of 596 Chinese participants. We further evaluated the associations of smoking-related CpGs with internal polycyclic aromatic hydrocarbon (PAH) biomarkers and their correlations with the expression of corresponding genes.We identified 318 CpGs whose methylation levels were associated with smoking at a genome-wide significance level (false discovery rate < 0.05), among which 161 CpGs annotated to 123 genes were not associated with smoking in recent studies of Europeans and African Americans. Of these smoking-related CpGs, methylation levels at 80 CpGs showed significant correlations with the expression of corresponding genes (including RUNX3, IL6R, PTAFR, ANKRD11, CEP135 and CDH23), and methylation at 15 CpGs was significantly associated with urinary 2-hydroxynaphthalene, the most representative internal monohydroxy-PAH biomarker for smoking.We identified DNA methylation markers associated with smoking in a Chinese population, including some markers that were also correlated with gene expression. Exposure to naphthalene, a byproduct of tobacco smoke, may contribute to smoking-related methylation.Zhu X, Li J, Deng S, Yu K, Liu X, Deng Q, Sun H, Zhang X, He M, Guo H, Chen W, Yuan J, Zhang B, Kuang D, He X, Bai Y, Han X, Liu B, Li X, Yang L, Jiang H, Zhang Y, Hu J, Cheng L, Luo X, Mei W, Zhou Z, Sun S, Zhang L, Liu C, Guo Y, Zhang Z, Hu FB, Liang L, Wu T. 2016. Genome-wide analysis of DNA methylation and cigarette smoking in Chinese. Environ Health Perspect 124:966-973;?http://dx.doi.org/10.1289/ehp.1509834.

Project description:ObjectivesUnderstanding how dementia risk is impacted by timing of smoking cessation has public health implications for prevention efforts. We investigated the relationship of cigarette smoking and cessation with dementia risk and cognitive decline in the Atherosclerosis Risk in Communities (ARIC) study.DesignOngoing prospective cohort study.SettingBegun in 1987-1989, ARIC was conducted in four US communities.ParticipantsA total of 13 002 men and women (25% African American) aged 52 to 75?years.MeasurementsAll-cause dementia was defined using standardized algorithms incorporating longitudinal cognitive data, proxy report, and hospital and death certificate dementia codes. Cognitive decline was measured using a composite cognitive score created from three tests measured at two time points (1996-1998 and 2011-2013). Smoking and cessation status were defined by self-report using data from 1987-1989 (visit 1) and 1996-1998 (visit 4). Incident dementia risk and differences in cognitive change by smoking status were estimated with Cox proportional hazards and linear regression models, respectively. To address smoking-related attrition, cognitive scores were imputed for living participants with incomplete cognitive testing.ResultsThe proportion of never, former, and current smokers was 44%, 41%, and 14%; 79% of former smokers quit 9?years or more before baseline. A total of 1347 participants developed dementia. After adjustment, compared with never smoking, the hazard ratio for all-cause dementia for current smoking was 1.33 (95% confidence interval [CI] = 1.12-1.59) and for recent quitting (<9 y before baseline) was 1.24 (95% CI = 1.01-1.52). Quitting 9?years or more before baseline was not associated with dementia. We found no differences in rates of cognitive decline by smoking status.ConclusionAlthough quitting at any time suggested benefit, dementia risk depended on time since smoking cessation. Our study highlights the importance of early midlife cessation to decrease dementia risk. J Am Geriatr Soc 68:337-345, 2020.

Project description:BackgroundDNA methylation has been hypothesized as a mechanism for explaining the association between smoking and adverse prostate cancer (PCa) outcomes. This study was aimed at assessing whether smoking is associated with prostate tumor DNA methylation and whether these alterations may explain in part the association of smoking with PCa recurrence and mortality.MethodsA total of 523 men had radical prostatectomy as their primary treatment, detailed smoking history data, long-term follow-up for PCa outcomes, and tumor tissue profiled for DNA methylation. Ninety percent of the men also had matched tumor gene expression data. A methylome-wide analysis was conducted to identify differentially methylated regions (DMRs) by smoking status. To select potential functionally relevant DMRs, their correlation with the messenger RNA (mRNA) expression of corresponding genes was evaluated. Finally, a smoking-related methylation score based on the top-ranked DMRs was created to assess its association with PCa outcomes.ResultsForty DMRs were associated with smoking status, and 10 of these were strongly correlated with mRNA expression (aldehyde oxidase 1 [AOX1], claudin 5 [CLDN5], early B-cell factor 1 [EBF1], homeobox A7 [HOXA7], lectin galactoside-binding soluble 3 [LGALS3], microtubule-associated protein τ [MAPT], protocadherin γ A [PCDHGA]/protocadherin γ B [PCDHGB], paraoxonase 3 [PON3], synaptonemal complex protein 2 like [SYCP2L], and zinc finger and SCAN domain containing 12 [ZSCAN12]). Men who were in the highest tertile for the smoking-methylation score derived from these DMRs had a higher risk of recurrence (odds ratio [OR], 2.29; 95% confidence interval [CI], 1.42-3.72) and lethal disease (OR, 4.21; 95% CI, 1.65-11.78) in comparison with men in the lower 2 tertiles.ConclusionsThis integrative molecular epidemiology study supports the hypothesis that smoking-associated tumor DNA methylation changes may explain at least part of the association between smoking and adverse PCa outcomes. Future studies are warranted to confirm these findings and understand the implications for improving patient outcomes. Cancer 2016;122:2168-77. © 2016 American Cancer Society.

Dataset Information

Cigarette smoking behaviors and time since quitting are associated with differential DNA methylation across the human genome.

Publications

Cigarette smoking behaviors and time since quitting are associated with differential DNA methylation across the human genome.

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