scholarly journals Prenatal smoke exposure, DNA methylation and a link between DRD1 and lung cancer

2019 ◽  
Vol 48 (4) ◽  
pp. 1377-1378
Author(s):  
Bríd M Ryan ◽  
Ana I Robles
Keyword(s):  
Lung Cancer ◽  
Dna Methylation ◽  
Smoke Exposure

scholarly journals DNA methylation signature of smoking in lung cancer is enriched for exposure signatures in newborn and adult blood

2018 ◽  
Author(s):  
K. M. Bakulski ◽  
J. Dou ◽  
N. Lin ◽  
S. J. London ◽  
J. A. Colacino
Keyword(s):  
Lung Cancer ◽  
Dna Methylation ◽  
Lung Tumors ◽  
Smoke Exposure ◽  
The Cancer Genome Atlas ◽  
Cigarette Smoke Exposure ◽  
Aberrant Methylation ◽  
Smoking During Pregnancy ◽  
Never Smokers ◽  
Meta Analyses

ABSTRACTBackgroundSmoking impacts DNA methylation genome-wide in blood of both newborns from maternal smoking during pregnancy and adults from personal smoking. Smoking causes lung cancer which involves aberrant methylation. We examined whether DNA methylation smoking signatures identified in blood of newborns and adults are detectable in lung tumors.MethodsWe compared smoking-related DNA methylation in lung adenocarcinomas (61 never smokers, 91 current smokers, and 238 former smokers) quantified with the Illumina450k BeadArray in The Cancer Genome Atlas with published large consortium meta-analyses of newborn and adult blood. We assessed whether CpG sites related to smoking in blood from newborns and adults were enriched in lung adenocarcinoma.ResultsTesting CpGs differentially methylated by smoke exposure (P<10−4) we identified 296 in lung tumors, while previous meta-analyses (False Discovery Rate (FDR)<0.05) identified 6,073 in newborn blood, and for adult smoking, 18,760 in blood. The lung signals were highly enriched for those seen in newborn (32 overlapping, Penrichment=1.2×10−19) and adult blood (86 overlapping, Penrichment = 9.5×10−49). The 65 genes annotated to CpGs differentially methylated in lung tumors, but not blood, were enriched for RNA processing ontologies.ConclusionsWe found highly significant overlap between smoking-related DNA methylation signals in lung cancer and those seen in blood from newborns, from in utero exposure, or adults, from their own exposure. These results suggest that some epigenetic alterations associated with cigarette smoke exposure are tissue specific, but others are common across tissues. These findings support the value of blood-based methylation biomarkers for assessing exposure effects in target tissues.

scholarly journals Response to: Prenatal smoke exposure, DNA methylation and a link between DRD1 and lung cancer

2019 ◽  
Vol 48 (4) ◽  
pp. 1378-1379
Author(s):  
Rebecca C Richmond ◽  
Matthew Suderman ◽  
Ryan Langdon ◽  
Caroline L Relton ◽  
George Davey Smith
Keyword(s):  
Lung Cancer ◽  
Dna Methylation ◽  
Smoke Exposure

scholarly journals Investigating the DNA methylation profile of e-cigarette use

2021 ◽  
Author(s):  
Rebecca C Richmond ◽  
Carlos Sillero Rejon ◽  
Jasmine N Khouja ◽  
Claire Prince ◽  
Alexander Board ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Dna Methylation ◽  
Cigarette Smoking ◽  
Normal Tissue ◽  
Smoke Exposure ◽  
Methylation Profile ◽  
Cigarette Use ◽  
Related Disease ◽  
Dna Methylation Profile ◽  
Methylation Score

AbstractRationale and objectivesLittle evidence exists on the health effects of e-cigarette use. DNA methylation may serve as a biomarker for exposure and could be predictive of future health risk. We aimed to investigate the DNA methylation profile of e-cigarette use.MethodsAmong 117 smokers, 117 non-smokers and 116 non-smoking vapers, we evaluated associations between e-cigarette use and epigenome-wide methylation from saliva. We tested associations between e-cigarette use and methylation scores known to predict smoking and smoking-related disease. We assessed the ability of a methylation score for predicting e-cigarette use and for discriminating lung cancer.Measurements and Main Results7 CpGs were identified in relation to e-cigarette use at p<1×10−5 and none at p<5.91×10−8. 13 CpGs were associated with smoking at p<1×10−5 and one at p<5.91×10−8. CpGs associated with e-cigarette use were largely distinct from those associated with smoking. There was strong enrichment of known smoking-related CpGs in the smokers but not the vapers. A methylation score for e-cigarette use showed poor prediction internally (AUC 0.55, 0.41-0.69) and externally (AUC 0.57, 0.36-0.74) compared with a smoking score (AUCs 0.80) and was less able to discriminate lung squamous cell carcinoma from adjacent normal tissue (AUC 0.64, 0.52-0.76 versus AUC 0.73, 0.61-0.85).ConclusionsThe DNA methylation profile for e-cigarette use is largely distinct from that of cigarette smoking, did not replicate in independent samples, and was unable to discriminate lung cancer from normal tissue. The extent to which methylation related to long-term e-cigarette use translates into chronic effects requires further investigation.Key MessagesWhat is the key question?Is there a DNA methylation signature of e-cigarette use and is it distinct from that of smoking?What is the bottom line?Smoke exposure is known to lead to widespread changes in DNA methylation which have been identified in different populations and samples, persist for many years after smoking cessation, and may act as a biomarker for smoking-related disease risk and mortality. Whether a similar methylation profile exists in relation to e-cigarette use has not been widely investigated.Why read on?We obtained saliva samples from 116 e-cigarette users and compared their DNA methylation profile with 117 smokers and 117 non-smokers. The e-cigarette users in this study had a minimal smoking history, and so we were able to distinguish the effects of e-cigarette use from those of smoke exposure. Overall, we found that the methylation profile associated with e-cigarette use is less pronounced and distinct from that associated with cigarette smoking.

scholarly journals Postnatal Smoke Exposure Further Increases the Hepatic Nicotine Metabolism in Prenatally Smoke Exposed Male Offspring and Is Linked with Aberrant Cyp2a5 Methylation

2020 ◽  
Vol 22 (1) ◽  
pp. 164
Author(s):  
Khosbayar Lkhagvadorj ◽  
Zhijun Zeng ◽  
Karolin F. Meyer ◽  
Laura P. Verweij ◽  
Wierd Kooistra ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Mrna Expression ◽  
Nicotine Dependence ◽  
Susceptibility Gene ◽  
Smoke Exposure ◽  
Adverse Outcomes ◽  
Male Offspring ◽  
Adult Offspring ◽  
Mrna Levels ◽  
Nicotine Metabolism

Prenatal smoke exposure (PreSE) is a risk factor for nicotine dependence, which is further enhanced by postnatal smoke exposure (PostSE). One susceptibility gene to nicotine dependence is Cytochrome P450 (CYP) 2A6, an enzyme responsible for the conversion of nicotine to cotinine in the liver. Higher CYP2A6 activity is associated with nicotine dependence and could be regulated through DNA methylation. In this study we investigated whether PostSE further impaired PreSE-induced effects on nicotine metabolism, along with Cyp2a5, orthologue of CYP2A6, mRNA expression and DNA methylation. Using a mouse model where prenatally smoke-exposed adult offspring were exposed to cigarette smoke for 3 months, enzyme activity, mRNA levels, and promoter methylation of hepatic Cyp2a5 were evaluated. We found that in male offspring, PostSE increased PreSE-induced cotinine levels and Cyp2a5 mRNA expression. In addition, both PostSE and PreSE changed Cyp2a5 DNA methylation in male groups. PreSE however decreased cotinine levels whereas it had no effect on Cyp2a5 mRNA expression or methylation. These adverse outcomes of PreSE and PostSE were most prominent in males. When considered in the context of the human health aspects, the combined effect of prenatal and adolescent smoke exposure could lead to an accelerated risk for nicotine dependence later in life.

scholarly journals Epigenome-wide association study of whole blood gene expression in Framingham Heart Study participants provides molecular insight into the potential role of CHRNA5 in cigarette smoking-related lung diseases

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Chen Yao ◽  
Roby Joehanes ◽  
Rory Wilson ◽  
Toshiko Tanaka ◽  
Luigi Ferrucci ◽  
...  
Keyword(s):  
Gene Expression ◽  
Lung Cancer ◽  
Dna Methylation ◽  
Cigarette Smoking ◽  
Association Study ◽  
Whole Blood ◽  
Lung Diseases ◽  
Epigenetic Modification ◽  
Blood Gene Expression ◽  
Increased Risk

Abstract Background DNA methylation is a key epigenetic modification that can directly affect gene regulation. DNA methylation is highly influenced by environmental factors such as cigarette smoking, which is causally related to chronic obstructive pulmonary disease (COPD) and lung cancer. To date, there have been few large-scale, combined analyses of DNA methylation and gene expression and their interrelations with lung diseases. Results We performed an epigenome-wide association study of whole blood gene expression in ~ 6000 individuals from four cohorts. We discovered and replicated numerous CpGs associated with the expression of cis genes within 500 kb of each CpG, with 148 to 1,741 cis CpG-transcript pairs identified across cohorts. We found that the closer a CpG resided to a transcription start site, the larger its effect size, and that 36% of cis CpG-transcript pairs share the same causal genetic variant. Mendelian randomization analyses revealed that hypomethylation and lower expression of CHRNA5, which encodes a smoking-related nicotinic receptor, are causally linked to increased risk of COPD and lung cancer. This putatively causal relationship was further validated in lung tissue data. Conclusions Our results provide a large and comprehensive association study of whole blood DNA methylation with gene expression. Expression platform differences rather than population differences are critical to the replication of cis CpG-transcript pairs. The low reproducibility of trans CpG-transcript pairs suggests that DNA methylation regulates nearby rather than remote gene expression. The putatively causal roles of methylation and expression of CHRNA5 in relation to COPD and lung cancer provide evidence for a mechanistic link between patterns of smoking-related epigenetic variation and lung diseases, and highlight potential therapeutic targets for lung diseases and smoking cessation.

scholarly journals Identification of a panel of sensitive and specific DNA methylation markers for squamous cell lung cancer

2008 ◽  
Vol 7 (1) ◽  
pp. 62 ◽  
Author(s):  
Paul P Anglim ◽  
Janice S Galler ◽  
Michael N Koss ◽  
Jeffrey A Hagen ◽  
Sally Turla ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Dna Methylation ◽  
Squamous Cell ◽  
Cell Lung Cancer ◽  
Squamous Cell Lung Cancer

scholarly journals Gene expression profiling of epigenetic chromatin modification enzymes and histone marks by cigarette smoke: implications for COPD and lung cancer

2016 ◽  
Vol 311 (6) ◽  
pp. L1245-L1258 ◽  
Author(s):  
Isaac K. Sundar ◽  
Irfan Rahman
Keyword(s):  
Gene Expression ◽  
Lung Cancer ◽  
Dna Methylation ◽  
Cigarette Smoke ◽  
Histone Modifications ◽  
Expression Patterns ◽  
Chromatin Modification ◽  
Gene Expression Patterns ◽  
Validation Data ◽  
Histone Marks

Chromatin-modifying enzymes mediate DNA methylation and histone modifications on recruitment to specific target gene loci in response to various stimuli. The key enzymes that regulate chromatin accessibility for maintenance of modifications in DNA and histones, and for modulation of gene expression patterns in response to cigarette smoke (CS), are not known. We hypothesize that CS exposure alters the gene expression patterns of chromatin-modifying enzymes, which then affects multiple downstream pathways involved in the response to CS. We have, therefore, analyzed chromatin-modifying enzyme profiles and validated by quantitative real-time PCR (qPCR). We also performed immunoblot analysis of targeted histone marks in C57BL/6J mice exposed to acute and subchronic CS, and of lungs from nonsmokers, smokers, and patients with chronic obstructive pulmonary disease (COPD). We found a significant increase in expression of several chromatin modification enzymes, including DNA methyltransferases, histone acetyltransferases, histone methyltransferases, and SET domain proteins, histone kinases, and ubiquitinases. Our qPCR validation data revealed a significant downregulation of Dnmt1, Dnmt3a, Dnmt3b, Hdac2, Hdac4, Hat1, Prmt1, and Aurkb. We identified targeted chromatin histone marks (H3K56ac and H4K12ac), which are induced by CS. Thus CS-induced genotoxic stress differentially affects the expression of epigenetic modulators that regulate transcription of target genes via DNA methylation and site-specific histone modifications. This may have implications in devising epigenetic-based therapies for COPD and lung cancer.

Sign in / Sign up

Export Citation Format

Share Document