Secondhand Tobacco Smoke Exposure Associations with DNA Methylation of the Aryl Hydrocarbon Receptor Repressor

Reynolds, Lindsay M.; Magid, Hoda S. Abdel; Gloria, C.; Lohman, Kurt; Barr, R. Graham; Kaufman, Joel D.; Hoeschele, Ina; Blaha, Michael J.; Navas‐Acien, Ana; Liu, Yongmei

doi:10.1093/ntr/ntw219

Cited by 28 publications

(37 citation statements)

References 49 publications

(77 reference statements)

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“…Similar DNA methylation patterns have been observed in lung tumours of smokers and second–hand smokers [ 32 ]. Hypomethylation of AHRR at cg05575921 has been linked to recent exposure to second–hand smoke [ 33 ], while others have reported significant associations between second–hand smoke exposure and differential DNA methylation in bladder cancer [ 34 ]. There was no association between misclassification of never smokers and co–habitation with, or other exposure to, smokers.…”

Section: Discussionmentioning

confidence: 99%

Epigenetic signatures of starting and stopping smoking

et al. 2018

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BackgroundMultiple studies have made robust associations between differential DNA methylation and exposure to cigarette smoke. But whether a DNA methylation phenotype is established immediately upon exposure, or only after prolonged exposure is less well–established. Here, we assess DNA methylation patterns from peripheral blood samples in current smokers in response to dose and duration of exposure, along with the effects of smoking cessation on DNA methylation in former smokers.MethodsDimensionality reduction was applied to DNA methylation data at 90 previously identified smoking–associated CpG sites for over 4900 individuals in the Generation Scotland cohort. K–means clustering was performed to identify clusters associated with current and never smoker status based on these methylation patterns. Cluster assignments were assessed with respect to duration of exposure in current smokers (years as a smoker), time since smoking cessation in former smokers (years), and dose (cigarettes per day).FindingsTwo clusters were specified, corresponding to never smokers (97·5% of whom were assigned to Cluster 1) and current smokers (81·1% of whom were assigned to Cluster 2). The exposure time point from which >50% of current smokers were assigned to the smoker–enriched cluster varied between 5 and 9 years in heavier smokers and between 15 and 19 years in lighter smokers. Low–dose former smokers were more likely to be assigned to the never smoker–enriched cluster in the first year following cessation. In contrast, a period of at least two years was required before the majority of former high–dose smokers were assigned to the never smoker–enriched cluster.InterpretationOur findings suggest that smoking–associated DNA methylation changes are a result of prolonged exposure to cigarette smoke, and can be reversed following cessation. The length of time in which these signatures are established and recovered is dose dependent. Should DNA methylation–based signatures of smoking status be predictive of smoking–related health outcomes, our findings may provide an additional criterion on which to stratify risk.

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Section: Discussionmentioning

confidence: 99%

Epigenetic signatures of starting and stopping smoking

et al. 2018

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“…Differential methylation of probes in AHRR is one of the most commonly replicated regions across EWAS of smoking-related phenotypes. Cg05575921 has served as marker of smoking status [ 26 ] and second-hand smoking [ 27 ] and has been associated with smoking quantity (pack-years) in ever smokers and quit time in past smokers [ 14 , 28 ]. Differential methylation of cg05575921 has been found associated with lung cancer, where cases had lower DNA methylation beta values than controls, even after adjusting for age, sex, smoking status, and pack-years [ 29 , 30 ].…”

Section: Discussionmentioning

confidence: 99%

Association of internal smoking dose with blood DNA methylation in three racial/ethnic populations

et al. 2018

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BackgroundLung cancer is the leading cause of cancer-related death. While cigarette smoking is the primary cause of this malignancy, risk differs across racial/ethnic groups. For the same number of cigarettes smoked, Native Hawaiians compared to whites are at greater risk and Japanese Americans are at lower risk of developing lung cancer. DNA methylation of specific CpG sites (e.g., in AHRR and F2RL3) is the most common blood epigenetic modification associated with smoking status. However, the influence of internal smoking dose, measured by urinary nicotine equivalents (NE), on DNA methylation in current smokers has not been investigated, nor has a study evaluated whether for the same smoking dose, circulating leukocyte DNA methylation patterns differ by race.MethodsWe conducted an epigenome-wide association study (EWAS) of NE in 612 smokers from three racial/ethnic groups: whites (n = 204), Native Hawaiians (n = 205), and Japanese Americans (n = 203). Genome-wide DNA methylation profiling of blood leukocyte DNA was measured using the Illumina 450K BeadChip array. Average β value, the ratio of signal from a methylated probe relative to the sum of the methylated and unmethylated probes at that CpG, was the dependent variables in linear regression models adjusting for age, sex, race (for pan-ethnic analysis), and estimated cell-type distribution.ResultsWe found that NE was significantly associated with six differentially methylated CpG sites (Bonferroni corrected p < 1.48 × 10−7): four in or near the FOXK2, PBX1, FNDC7, and FUBP3 genes and two in non-annotated genetic regions. Higher levels of NE were associated with increasing methylation beta-valuesin all six sites. For all six CpG sites, the association was only observed in Native Hawaiians, suggesting that the influence of smoking dose on DNA methylation patterns is heterogeneous across race/ethnicity (p interactions < 8.8 × 10−8). We found two additional CpG sites associated with NE in only Native Hawaiians.ConclusionsIn conclusion, internal smoking dose was associated with increased DNA methylation in circulating leukocytes at specific sites in Native Hawaiian smokers but not in white or Japanese American smokers.Electronic supplementary materialThe online version of this article (10.1186/s13148-018-0543-7) contains supplementary material, which is available to authorized users.

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“…Because our samples were derived from a cohort of adolescents and the frequency of actual reported smoking was relatively low (20% current smokers; mean = 0.520 pack years; SD = 0.724 pack years) we expected the derived smoking scores to be approximately zero, as seen in the different purified blood cell types (Figure 3). It is plausible that the higher derived smoking scores observed in buccal epithelial cells and nasal epithelial cells reflect both passive exposure to tobacco smoke 29 and exposure to other environmental toxins (e.g. air pollution) that influence DNAm at similar sites to smoking 30 .…”

Section: Measures Of Age and Environmental Exposure Derived From Dnammentioning

confidence: 99%

Assessing the co-variability of DNA methylation across peripheral cells and tissues: implications for the interpretation of findings in epigenetic epidemiology

Hannon

Mansell

Burrage

et al. 2020

Preprint

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Key Messages We identified major differences in DNA methylation between blood cell types and peripheral tissues, with each sample type being characterized by a unique DNA methylation signature across multiple loci. Estimates of DNAmAge and tobacco smoking from DNA methylation data can be highly variable across different sample types collected from the same individual at the same time. While individual blood cell types did predict more of the variation in whole blood compared to buccal epithelial and nasal epithelial cells, the percentage of variance explained was still small. Instead our data indicate that at the majority of sites, variation in multiple blood cell types additively combines to drive variation in DNA methylation in whole blood. There are subset of sites where variable DNA methylation detected in whole blood can be attributed to variation in a single blood cell type.

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Secondhand Tobacco Smoke Exposure Associations with DNA Methylation of the Aryl Hydrocarbon Receptor Repressor

Cited by 28 publications

References 49 publications

Epigenetic signatures of starting and stopping smoking

Epigenetic signatures of starting and stopping smoking

Association of internal smoking dose with blood DNA methylation in three racial/ethnic populations

Assessing the co-variability of DNA methylation across peripheral cells and tissues: implications for the interpretation of findings in epigenetic epidemiology

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