Correlation of Smoking-Associated DNA Methylation Changes in Buccal Cells With DNA Methylation Changes in Epithelial Cancer

Teschendorff, Andrew E.; Yang, Zhen; Wong, Andrew; Pipinikas, Christodoulos P.; Jiao, Yinming; Jones, Allison; Anjum, Shahzia; Hardy, Rebecca; Salvesen, Helga B.; Thirlwell, Christina; Janes, Sam M.; Kuh, Diana; Widschwendter, Martin

doi:10.1001/jamaoncol.2015.1053

Cited by 179 publications

(287 citation statements)

References 50 publications

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“…We used the identified frailty-associated loci to construct a smoking index (SI) according to Teschendorff et al's algorithm, 25 to measure the deviation of DNA methylation in a given sample from a normal reference, with the mean taken over from the identified loci. In more detail, we computed the mean b value (m c ) and standard deviation (s c ) across never smokers of the given data set, and then defined the SI as where W c is ¡1(C1) if the smoking-associated CpG, c, is hypomethylated (hypermethylated) in smokers and where b cs is the b value of this CpG in samples s. 25 We calculated the SI for each participant and assessed its association with the FI by mixed linear regression models with adjustment for potential covariates in the validation panel.…”

Section: Statistical Analysesmentioning

confidence: 99%

“…In more detail, we computed the mean b value (m c ) and standard deviation (s c ) across never smokers of the given data set, and then defined the SI as where W c is ¡1(C1) if the smoking-associated CpG, c, is hypomethylated (hypermethylated) in smokers and where b cs is the b value of this CpG in samples s. 25 We calculated the SI for each participant and assessed its association with the FI by mixed linear regression models with adjustment for potential covariates in the validation panel. Subsequently, we used restricted cubic spline functions using the SAS macro from Desquilbet et al to evaluate the dose-response relationship of the SI with the FI, controlling for age, sex, alcohol consumption, and the leukocyte distribution.…”

Section: Statistical Analysesmentioning

confidence: 99%

“…[20][21][22][23][24] Teschendorff et al constructed a smoking index based on 1,501 smoking-related CpG sites and illustrated that such DNA methylation signatures of smoking could be useful indicators of smoking-induced health disorders. 25 Hence, we hypothesized that smoking-induced DNA methylation might also be correlated with frailty. We therefore performed a comprehensive analysis of the associations of selfreported smoking indicators, serum cotinine levels and smoking-related DNA methylation biomarkers with frailty in a large population-based study of older adults in Germany and evaluated a smoking-related methylation-based predictor of frailty.…”

Section: Introductionmentioning

confidence: 99%

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Tobacco smoking and smoking-related DNA methylation are associated with the development of frailty among older adults

et al. 2017

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Tobacco smoking is a preventable environmental factor that contributes to a wide spectrum of age-related health outcomes; however, its association with the development of frailty is not yet well established. We examined the associations of self-reported smoking indicators, serum cotinine levels and smoking-related DNA methylation biomarkers with a quantitative frailty index (FI) in 2 independent subsets of older adults (age 50-75) recruited in Saarland, Germany in 2000 -2002 (discovery set: n D 978, validation set: n D 531). We obtained DNA methylation profiles in whole blood samples by Illumina HumanMethylation450 BeadChip and calculated the FI according to the method of Mitnitski and Rockwood. Mixed linear regression models were implemented to assess the associations between smoking indicators and the FI. After controlling for potential covariates, current smoking, cumulative smoking exposure (pack-years), and time after smoking cessation (years) were significantly associated with the FI (P-value < 0.05). In the discovery panel, 17 out of 151 previously identified smoking-related CpG sites were associated with the FI after correction for multiple testing (FDR < 0.05). Nine of them survived in the validation phase and were designated as frailty-associated loci. A smoking index (SI) based on the 9 loci manifested a monotonic association with the FI. In conclusion, this study suggested that epigenetic alterations could play a role in smoking-associated development of frailty. The identified CpG sites have the potential to be prognostic biomarkers of frailty and frailty-related health outcomes. Our findings and the underlying mechanisms should be followed up in further, preferably longitudinal studies.

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Section: Statistical Analysesmentioning

confidence: 99%

Section: Statistical Analysesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Tobacco smoking and smoking-related DNA methylation are associated with the development of frailty among older adults

et al. 2017

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“…More recently, Teschendroff et al [45] examined the link between the buccal epithelial epigenome-wide association studies and DNA methylation (DNAme) patterns in epithelial malignancy, including lung cancer. DNAme is an epigenetic alteration that had been implicated in carcinogenesis [44] .…”

Section: Buccal Epithelium and Lung Cancermentioning

confidence: 99%

Buccal Epithelium, Cigarette Smoking, and Lung Cancer: Review of the Literature

Saba

Halytskyy²,

Saleem³

et al. 2017

Oncology

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Lung cancer is currently the leading cause of cancer-related mortality among men and women in the United States, and optimal screening methods are still lacking. The field effect is a well-supported phenomenon wherein a noxious stimulus triggers genetic, epigenetic and molecular changes that are widespread throughout the entire exposed organ system. The buccal epithelium is an easily accessible part of the respiratory tree that has good potential of yielding a surrogate marker for the field effect in cigarette smokers, and thus, a noninvasive, reliable lung cancer screening method. Herein, we review the literature on the relationship between the buccal epithelium, cigarette smoking, and lung cancer.

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“…Differences in DNA methylation levels have also been connected to many different diseases like diabetes (Nilsson et al 2014) or Alzheimer's disease (De Jager et al 2014). Furthermore, differential DNA methylation plays a role in many cancers, such as medulloblastoma (Hovestadt et al 2014) and B-cell lymphoma (Kretzmer et al 2015), and connects risk factors like age (Teschendorff et al 2010) and smoking (Teschendorff et al 2015) with cancer.…”

mentioning

confidence: 99%

metilene: fast and sensitive calling of differentially methylated regions from bisulfite sequencing data

et al. 2015

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The detection of differentially methylated regions (DMRs) is a necessary prerequisite for characterizing different epigenetic states. We present a novel program, metilene, to identify DMRs within whole-genome and targeted data with unrivaled specificity and sensitivity. A binary segmentation algorithm combined with a two-dimensional statistical test allows the detection of DMRs in large methylation experiments with multiple groups of samples in minutes rather than days using off-the-shelf hardware. metilene outperforms other state-of-the-art tools for low coverage data and can estimate missing data. Hence, metilene is a versatile tool to study the effect of epigenetic modifications in differentiation/development, tumorigenesis, and systems biology on a global, genome-wide level. Whether in the framework of international consortia with dozens of samples per group, or even without biological replicates, it produces highly significant and reliable results.

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Correlation of Smoking-Associated DNA Methylation Changes in Buccal Cells With DNA Methylation Changes in Epithelial Cancer

Abstract: These data point toward buccal cells as being a more appropriate source of tissue than blood to conduct EWASs for smoking-related epithelial cancers.

Cited by 179 publications

References 50 publications

Tobacco smoking and smoking-related DNA methylation are associated with the development of frailty among older adults

Tobacco smoking and smoking-related DNA methylation are associated with the development of frailty among older adults

Buccal Epithelium, Cigarette Smoking, and Lung Cancer: Review of the Literature

metilene: fast and sensitive calling of differentially methylated regions from bisulfite sequencing data

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