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.

Lung cancer risk stratification using methylation profile in the oral epithelium

2018 ◽  
Vol 27 (2) ◽  
pp. 87-92 ◽  
Author(s):  
Hiroaki Harada ◽  
Kazuaki Miyamaoto ◽  
Masami Kimura ◽  
Tetsuro Ishigami ◽  
Kiyomi Taniyama ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Dna Methylation ◽  
Cancer Risk ◽  
Risk Stratification ◽  
Lung Cancer Risk ◽  
Cancer Risk Assessment ◽  
Oral Epithelium ◽  
Specific Gene ◽  
Aberrant Methylation ◽  
Cancer Genes

Background Assuming that the entire airway is affected by the same inhaled carcinogen, similar molecular alterations may occur in the lung and oral cavity. Thus, we hypothesized that DNA methylation profiles in the oral epithelium may be a promising biomarker for lung cancer risk stratification. Methods A methylation-specific polymerase chain reaction was performed on oral epithelium from 16 patients with lung cancer and 32 controls without lung cancer. Genes showing aberrant methylation profiles in the oral epithelium were compared between patients and controls. Results The analysis revealed that HOXD11 and PCDHGB6 were methylated more frequently in patients than in controls ( p = 0.0055 and p = 0.0247, respectively). Combined analyses indicated that 8 of 16 (50%) patients and 3 of 32 (9.4%) controls showed DNA methylation in both genes ( p = 0.0016). Among the population limited to current and former smokers, 6 of 11 (54.5%) patients showed methylation in both genes, compared to 1 of 17 (5.9%) controls ( p = 0.0037). In a subgroup analysis limited to the population above 50-years old, 8 of 16 (50%) patients and 2 of 16 (12.5%) controls showed methylation in both genes ( p = 0.0221). Conclusions The results of this study indicate that specific gene methylation in the oral epithelium might be a promising biomarker for lung cancer risk assessment, especially among smokers. Risk stratification through the analysis of DNA methylation profiles in the oral epithelium may be a useful and less invasive first-step approach in an efficient two-step lung cancer screening strategy.

scholarly journals Prenatal cigarette smoke exposure slightly alters neurobehavioral development in neonatal rats: Implications for developmental origins of health and disease (DoHAD)

2020 ◽  
Vol 107 (1) ◽  
pp. 55-66
Author(s):  
B. Mammel ◽  
T. Kvárik ◽  
Zs. Szabó ◽  
J. Gyarmati ◽  
T. Ertl ◽  
...  
Keyword(s):  
Cigarette Smoke ◽  
Motor Coordination ◽  
Smoke Exposure ◽  
Whole Body ◽  
Cigarette Smoke Exposure ◽  
Control Group ◽  
Developmental Origins ◽  
Smoking During Pregnancy ◽  
Neurobehavioral Development ◽  
Health And Disease

AbstractNumerous studies indicate that smoking during pregnancy exerts harmful effects on fetal brain development. The aim of this study was to determine the influence of maternal smoking during pregnancy on the early physical and neurobehavioral development of newborn rats. Wistar rats were subjected to whole-body smoke exposure for 2 × 40 min daily from the day of mating until day of delivery. For this treatment, a manual closed-chamber smoking system and 4 research cigarettes per occasion were used. After delivery the offspring were tested daily for somatic growth, maturation of facial characteristics and neurobehavioral development until three weeks of age. Motor coordination tests were performed at 3 and 4 weeks of age. We found that prenatal cigarette smoke exposure did not alter weight gain or motor coordination. Critical physical reflexes indicative of neurobehavioral development (eyelid reflex, ear unfolding) appeared significantly later in pups prenatally exposed to smoke as compared to the control group. Prenatal smoke exposure also resulted in a delayed appearance of reflexes indicating neural maturity, including hind limb grasping and forelimb placing reflexes. In conclusion, clinically relevant prenatal exposure to cigarette smoke results in slightly altered neurobehavioral development in rat pups. These findings suggest that chronic exposure of pregnant mothers to cigarette smoke (including passive smoking) results in persisting alterations in the developing brain, which may have long-lasting consequences supporting the concept of developmental origins of health and disease (DoHAD).

scholarly journals Frequent DNA methylation changes in cancerous and noncancerous lung tissues from smokers with non-small cell lung cancer

Mutagenesis ◽  
2020 ◽  
Author(s):  
Kristina Daniunaite ◽  
Agne Sestokaite ◽  
Raimonda Kubiliute ◽  
Kristina Stuopelyte ◽  
Eeva Kettunen ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Dna Methylation ◽  
Methylation Status ◽  
Small Cell ◽  
Study Cohort ◽  
Tumour Suppressor Genes ◽  
Epigenetic Changes ◽  
Small Cell Lung ◽  
Specific Pcr ◽  
Never Smokers

Abstract Cancer deaths account for nearly 10 million deaths worldwide each year, with lung cancer (LCa) as the leading cause of cancer-related death. Smoking is one of the major LCa risk factors, and tobacco-related carcinogens are potent mutagens and epi-mutagens. In the present study, we aimed to analyse smoking-related epigenetic changes in lung tissues from LCa cases. The study cohort consisted of paired LCa and noncancerous lung tissues (NLT) from 104 patients, 90 of whom were smokers or ex-smokers (i.e. ever smokers) at the time of diagnosis. DNA methylation status of tumour suppressor genes DAPK1, MGMT, p16, RASSF1 and RARB was screened by means of methylation-specific PCR (MSP) and further analysed quantitatively by pyrosequencing. Methylation of at least one gene was detected in 59% (61 of 104) of LCa samples and in 39% (41 of 104) of NLT. DAPK1 and RASSF1 were more frequently methylated in LCa than in NLT (P = 0.022 and P = 0.041, respectively). The levels of DNA methylation were higher in LCa than NLT at most of the analysed CpG positions. More frequent methylation of at least one gene was observed in LCa samples of ever smokers (63%, 57 of 90) as compared with never smokers (36%, 5 of 14; P = 0.019). In the ever smokers group, methylation of the genes also occurred in NLT, but was rare or absent in the samples of never smokers. Among the current smokers, RASSF1 methylation in LCa showed association with the number of cigarettes smoked per day (P = 0.017), whereas in NLT it was positively associated with the duration of smoking (P = 0.039). Similarly, p16 methylation in LCa of current smokers correlated with the larger number of cigarettes smoked per day (P = 0.047). Overall, DNA methylation changes were present in both cancerous and noncancerous tissues of LCa patients and showed associations with smoking-related parameters.

scholarly journals Impact of acute exposure to cigarette smoke on airway gene expression

2018 ◽  
Vol 50 (9) ◽  
pp. 705-713 ◽  
Author(s):  
E. Billatos ◽  
A. Faiz ◽  
Y. Gesthalter ◽  
A. LeClerc ◽  
Y. O. Alekseyev ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Lung Cancer ◽  
Cigarette Smoke ◽  
Smoke Exposure ◽  
Acute Exposure ◽  
Cigarette Smoke Exposure ◽  
Airway Epithelial ◽  
Long Term Effects ◽  
Chronic Smoking

Background: Understanding effects of acute smoke exposure (ASE) on airway epithelial gene expression and their relationship with the effects of chronic smoke exposure may provide biological insights into the development of smoking-related respiratory diseases. Methods: Bronchial airway epithelial cell brushings were collected from 63 individuals without recent cigarette smoke exposure and before and 24 h after smoking three cigarettes. RNA from these samples was profiled on Affymetrix Human Gene 1.0 ST microarrays. Results: We identified 91 genes differentially expressed 24 h after ASE (false discovery rate < 0.25). ASE induced genes involved in xenobiotic metabolism, oxidative stress, and inflammation and repressed genes related to cilium morphogenesis and cell cycle. While many genes altered by ASE are altered similarly in chronic smokers, metallothionein genes are induced by ASE and suppressed in chronic smokers. Metallothioneins are also suppressed in current and former smokers with lung cancer relative to those without lung cancer. Conclusions: Acute exposure to as little as three cigarettes and chronic smoking induce largely concordant changes in airway epithelial gene expression. Differences in short-term and long-term effects of smoking on metallothionein expression and their relationship to lung cancer requires further study given these enzymes’ role in the oxidative stress response.

scholarly journals The Role of DNA Methylation in the Development and Progression of Lung Adenocarcinoma

2007 ◽  
Vol 23 (1-2) ◽  
pp. 5-30 ◽  
Author(s):  
Keith M. Kerr ◽  
Janice S. Galler ◽  
Jeffrey A. Hagen ◽  
Peter W. Laird ◽  
Ite A. Laird-Offringa
Keyword(s):  
United States ◽  
Lung Cancer ◽  
Dna Methylation ◽  
Lung Adenocarcinoma ◽  
Western Europe ◽  
Cpg Islands ◽  
The United States ◽  
Smoke Inhalation ◽  
Genetic Changes ◽  
Never Smokers

Lung cancer, caused by smoking in ∼87% of cases, is the leading cause of cancer death in the United States and Western Europe. Adenocarcinoma is now the most common type of lung cancer in men and women in the United States, and the histological subtype most frequently seen in never-smokers and former smokers. The increasing frequency of adenocarcinoma, which occurs more peripherally in the lung, is thought to be at least partially related to modifications in cigarette manufacturing that have led to a change in the depth of smoke inhalation. The rising incidence of lung adenocarcinoma and its lethal nature underline the importance of understanding the development and progression of this disease. Alterations in DNA methylation are recognized as key epigenetic changes in cancer, contributing to chromosomal instability through global hypomethylation, and aberrant gene expression through alterations in the methylation levels at promoter CpG islands. The identification of sequential changes in DNA methylation during progression and metastasis of lung adenocarcinoma, and the elucidation of their interplay with genetic changes, will broaden our molecular understanding of this disease, providing insights that may be applicable to the development of targeted drugs, as well as powerful markers for early detection and patient classification.

Passive Cigarette Smoke Exposure, Genetic Variants and Breast Cancer Among Never-Smokers

2010 ◽  
Vol 20 (9) ◽  
pp. 692-693 ◽  
Author(s):  
L.N. Anderson ◽  
M. Cotterchio ◽  
L. Mirea ◽  
N. Kreiger ◽  
H. Ozcelik
Keyword(s):  
Breast Cancer ◽  
Cigarette Smoke ◽  
Genetic Variants ◽  
Smoke Exposure ◽  
Cigarette Smoke Exposure ◽  
Never Smokers

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 No impact of passive smoke on the somatic profile of lung cancers in never-smokers

2015 ◽  
Vol 45 (5) ◽  
pp. 1415-1425 ◽  
Author(s):  
Sébastien Couraud ◽  
Didier Debieuvre ◽  
Lionel Moreau ◽  
Patrick Dumont ◽  
Jacques Margery ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Passive Smoking ◽  
Smoke Exposure ◽  
Nonsignificant Trend ◽  
Lung Cancers ◽  
Significant Difference ◽  
Passive Smoke ◽  
Cumulative Duration ◽  
Never Smokers ◽  
Never Smoker

EGFR and HER2 mutations and ALK rearrangement are known to be related to lung cancer in never-smokers, while KRAS, BRAF and PIK3CA mutations are typically observed among smokers. There is still debate surrounding whether never-smokers exposed to passive smoke exhibit a “smoker-like” somatic profile compared with unexposed never-smokers.Passive smoke exposure was assessed in the French BioCAST/IFCT-1002 never-smoker lung cancer cohort and routine molecular profiles analyses were compiled.Of the 384 patients recruited into BioCAST, 319 were tested for at least one biomarker and provided data relating to passive smoking. Overall, 219 (66%) reported having been exposed to passive smoking. No significant difference was observed between mutation frequency and passive smoke exposure (EGFR mutation: 46% in never exposed versus 41% in ever exposed; KRAS: 7% versus 7%; ALK: 13% versus 11%; HER2: 4% versus 5%; BRAF: 6% versus 5%; PIK3CA: 4% versus 2%). We observed a nonsignificant trend for a negative association between EGFR mutation and cumulative duration of passive smoke exposure. No association was found for other biomarkers.There is no clear association between passive smoke exposure and somatic profile in lifelong, never-smoker lung cancer.

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