Global methylation profiles in buccal cells of long-term smokers and moist snuff consumers

Jessen, Walter J.; Borgerding, Michael F.; Prasad, G.L.

doi:10.1080/1354750x.2018.1466367

Cited by 15 publications

(15 citation statements)

References 59 publications

(77 reference statements)

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“…Our top hit identified in the SS model (cg05575921, p-value=4.54E-83) is within the AHRR gene, a well-known locus that acts in the aryl hydrocarbon receptor signaling cascade. This CpG was hypomethylated in current-smokers compared to non-smokers, as reported in other peripheral tissues including blood (9-12), lung (17,18), adipose tissue (19), and buccal cells (20). Further, 13 additional GWS DMS in AHRR were detected (minimum p-value = 5.73E-8), of which seven were previously described.…”

Section: Discussionsupporting

confidence: 65%

“…DNA methylation (DNAm), one of the most studied epigenetic mechanisms, has been previously shown to be associated with smoking behavior. Epigenome-wide association studies (EWAS) approaches have identified epigenomic biomarkers associated with smoking in multiple tissues: blood (9)(10)(11)(12)(13)(14)(15), newborn blood (16), lung (17,18), adipose tissue (19), buccal cells (20), and saliva (21)). While a large number of CpG sites have been associated with tobacco smoking status (SS), few studies to date have examined epigenomic changes associated with ND.…”

Section: Introductionmentioning

confidence: 99%

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Dissecting the Epigenomic Differences between Smoking and Nicotine Dependence in a Veteran Cohort

Nagamatsu

Pietrzak

Krystal

et al. 2021

Preprint

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Background: Smoking is a serious public health issue linked to more than 8 million deaths per year worldwide. It also may lead to nicotine dependence (ND). Smoking can induce long-lasting epigenetic changes. Although epigenetic alterations related to tobacco smoke have been largely studied, few works have investigated ND and its interaction with smoking status (SS). Objective: We investigated the peripheral epigenomic profile of SS and ND in a U.S. male veteran cohort. Methods: DNA from saliva was collected from 1,135 European American (EA) male U.S. military veterans. DNAm was assessed using the Illumina Infinium Human MethylationEPIC BeadChip array. SS was evaluated as: current smokers (n=137; 12.1%) and non-current smokers (never and former smokers; n=998; 87.9%). ND was assessed using the Fagerstrom Test for Nicotine Dependence (FTND). EWAS and co-methylation analyses were conducted for SS and ND. Results: A total of 450 and 22 genome-wide significant differentially methylated sites (DMS) were associated with SS and ND, respectively (fifteen overlapped sites). We identified 97 DMS (43 genes) in SS-EWAS previously reported in the literature, including AHRR, and F2RL3 genes (p-value range: 1.95x10-83 to 4.5x10-33). ND novel DMS mapped to NEUROG1, ANPEP, and SLC29A1. Co-methylation analysis identified 386 modules (11 SS-related and 19 ND-related). SS-related modules showed enrichment for alcoholism, chemokine signaling pathway, and neurogenesis; while ND-related modules were enriched for cellular adhesion, and nicotine addiction. Conclusions: This study confirms previous findings and identifies novel and -potentially specific - epigenetic signatures for SS and ND in a sample of EA male veterans.

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Section: Discussionsupporting

confidence: 65%

Section: Introductionmentioning

confidence: 99%

Dissecting the Epigenomic Differences between Smoking and Nicotine Dependence in a Veteran Cohort

Nagamatsu

Pietrzak

Krystal

et al. 2021

Preprint

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“…A plethora of studies exist that show significantly different methylation patterns in smokers compared to non-smokers in different tissues [2, 8–22] and in the context of smoke-related diseases like cancer [23] or chronic obstructive pulmonary disease (COPD) [21]. The best-replicated gene-specific association of differential methylation with smoking is attributed to the aryl-hydrocarbon receptor repressor AHRR across various tissues and cell types [8, 10, 12–14, 16, 17, 20, 22, 24, 25]. AHRR is a core regulator in the aryl hydrocarbon receptor (AhR) signalling cascade, modulating dioxin toxicity pathways involving Cytochrome P450, most likely in a cell-specific manner [26].…”

Section: Introductionmentioning

confidence: 99%

“…AHRR is a core regulator in the aryl hydrocarbon receptor (AhR) signalling cascade, modulating dioxin toxicity pathways involving Cytochrome P450, most likely in a cell-specific manner [26]. Most EWAS that assessed the role of CpG methylation in tobacco-related xenobiotic metabolism analysed leukocytes, but some also analysed airway epithelial cells [27] and buccal cells [12, 21, 22]. These cell types are located at the interface to the environment and form a mechanical and physiological barrier.…”

Section: Introductionmentioning

confidence: 99%

A combined epigenome- and transcriptome-wide association study of the oral masticatory mucosa assigns CYP1B1 a central role for epithelial health in smokers

et al. 2019

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Background The oral mucosa has an important role in maintaining barrier integrity at the gateway to the gastrointestinal and respiratory tracts. Smoking is a strong environmental risk factor for the common oral inflammatory disease periodontitis and oral cancer. Cigarette smoke affects gene methylation and expression in various tissues. This is the first epigenome-wide association study (EWAS) that aimed to identify biologically active methylation marks of the oral masticatory mucosa that are associated with smoking. Results Ex vivo biopsies of 18 current smokers and 21 never smokers were analysed with the Infinium Methylation EPICBeadChip and combined with whole transcriptome RNA sequencing (RNA-Seq; 16 mio reads per sample) of the same samples. We analysed the associations of CpG methylation values with cigarette smoking and smoke pack year (SPY) levels in an analysis of covariance (ANCOVA). Nine CpGs were significantly associated with smoking status, with three CpGs mapping to the genetic region of CYP1B1 (cytochrome P450 family 1 subfamily B member 1; best p = 5.5 × 10 −8 ) and two mapping to AHRR (aryl-hydrocarbon receptor repressor; best p = 5.9 × 10 −9 ). In the SPY analysis, 61 CpG sites at 52 loci showed significant associations of the quantity of smoking with changes in methylation values. Here, the most significant association located to the gene CYP1B1 , with p = 4.0 × 10 −10 . RNA-Seq data showed significantly increased expression of CYP1B1 in smokers compared to non-smokers ( p = 2.2 × 10 −14 ), together with 13 significantly upregulated transcripts. Six transcripts were significantly downregulated. No differential expression was observed for AHRR . In vitro studies with gingival fibroblasts showed that cigarette smoke extract directly upregulated the expression of CYP1B1. Conclusion This study validated the established role of CYP1B1 and AHRR in xenobiotic metabolism of tobacco smoke and highlights the importance of epigenetic regulation for these genes. For the first time, we give evidence of this role for the oral masticatory mucosa. Electronic supplementary material The online version of this article (10.1186/s13148-019-0697-y) contains supplementary material, which is available to authorized users.

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“…This study used a different swab type (Catch-All Sample Collection Swabs) with softer spongelike brushes possibly associated with less bleeding, and thus less contamination. On the other hand, a recent dataset of 120 samples related to tobacco usage from Jessen et al [32] was listed as originating from buccal cells, but showed an unusually low buccal content more typical of saliva datasets [28,33] as shown in Supplemental Figure S1. The authors reported that these buccal samples 'were collected in water by vigorously swishing' while the subjects rinsed their mouth, which may explain why the samples actually resemble the saliva.…”

Section: Lower-purity Buccal Samples Occur Commonlymentioning

confidence: 99%

Don’t brush off buccal data heterogeneity

et al. 2019

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Buccal epithelial cells are among the most clinically accessible tissues and are increasingly being used to identify epigenetic disease patterns. However, substantial variation in buccal DNA methylation patterns indicates heterogeneity of cell types within and between samples, raising questions of data quality. We systematically estimated cell-type composition for a large collection of buccal and saliva samples from 11 published studies of DNA methylation. In these we identified numerous cases of buccal samples with questionable purity, which may be affected by sampling from individuals with neurodevelopmental disorders, and by the brushes used for sample collection. Further challenges are involved in comparisons with tissues such as saliva, in which buccal component varies widely. We propose a reference-based method of correcting for buccal purity that reduces unwanted variation while preserving cross-tissue differences. Our work demonstrates the wide variation of buccal quality in epigenetic studies and suggests a possible approach to overcome this issue.

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Global methylation profiles in buccal cells of long-term smokers and moist snuff consumers

Abstract: Chronic cigarette smoking causes hyper- and hypo-methylation of genes that could contribute to smoking-related diseases. These results help place combustible and non-combustible tobacco products along a risk continuum and provide additional insights into the effects of tobacco consumption.

Cited by 15 publications

References 59 publications

Dissecting the Epigenomic Differences between Smoking and Nicotine Dependence in a Veteran Cohort

Dissecting the Epigenomic Differences between Smoking and Nicotine Dependence in a Veteran Cohort

A combined epigenome- and transcriptome-wide association study of the oral masticatory mucosa assigns CYP1B1 a central role for epithelial health in smokers

Don’t brush off buccal data heterogeneity

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