Fluorene exposure among PAH-exposed workers is associated with epigenetic markers related to lung cancer

ObjectivesExposure to high-molecular-weight polycyclic aromatic hydrocarbons (PAHs) may cause cancer in chimney sweeps and creosote-exposed workers, however, knowledge about exposure to low-molecular-weight PAHs in relation to cancer risk is limited. In this study, we aimed to investigate occupational exposure to the low-molecular-weight PAHs phenanthrene and fluorene in relation to different cancer biomarkers.MethodsWe recruited 151 chimney sweeps, 19 creosote-exposed workers and 152 unexposed workers (controls), all men. We measured monohydroxylated metabolites of phenanthrene and fluorene in urine using liquid chromatography coupled to tandem mass spectrometry. We measured, in peripheral blood, the cancer biomarkers telomere length and mitochondrial DNA copy number using quantitative PCR; and DNA methylation of F2RL3 and AHRR using pyrosequencing.ResultsMedian PAH metabolite concentrations were higher among chimney sweeps (up to 3 times) and creosote-exposed workers (up to 353 times), compared with controls (p<0.001; adjusted for age and smoking). ∑OH-fluorene (sum of 2-hydroxyfluorene and 3-hydroxyfluorene) showed inverse associations with percentage DNA methylation of F2RL3 and AHRR in chimney sweeps (B (95% CI)=–2.7 (–3.9 to –1.5) for F2RL3_cg03636183, and –7.1 (–9.6 to –4.7) for AHRR_cg05575921: adjusted for age and smoking), but not in creosote-exposed workers. In addition, ∑OH-fluorene showed a 42% mediation effect on the inverse association between being a chimney sweep and DNA methylation of AHRR CpG2.ConclusionsChimney sweeps and creosote-exposed workers were occupationally exposed to low-molecular-weight PAHs. Increasing fluorene exposure, among chimney sweeps, was associated with lower DNA methylation of F2RL3 and AHRR, markers for increased lung cancer risk. These findings warrant further investigation of fluorene exposure and toxicity.

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Randomized phase III trial of low-molecular-weight heparin enoxaparin in addition to standard treatment in small-cell lung cancer: the RASTEN trial

Annals of Oncology ◽

10.1093/annonc/mdx716 ◽

2018 ◽

Vol 29 (2) ◽

pp. 398-404 ◽

Cited By ~ 29

Author(s):

L. Ek ◽

E. Gezelius ◽

B. Bergman ◽

P.O. Bendahl ◽

H. Anderson ◽

...

Keyword(s):

Lung Cancer ◽

Molecular Weight ◽

Small Cell Lung Cancer ◽

Low Molecular Weight Heparin ◽

Standard Treatment ◽

Small Cell ◽

Phase Iii ◽

Low Molecular Weight ◽

Small Cell Lung ◽

Phase Iii Trial

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Comparison of plasma from healthy nonsmokers, smokers, and lung cancer patients: Pattern-based differentiation profiling of low molecular weight proteins and peptides by magnetic bead technology with MALDI-TOF MS

Biomarkers ◽

10.3109/1354750x.2012.657245 ◽

2012 ◽

Vol 17 (3) ◽

pp. 223-230 ◽

Cited By ~ 10

Author(s):

Syed G. Musharraf ◽

Naghma Hashmi ◽

M. Iqbal Choudhary ◽

Nadeem Rizvi ◽

Ahmed Usman ◽

...

Keyword(s):

Lung Cancer ◽

Molecular Weight ◽

Cancer Patients ◽

Magnetic Bead ◽

Low Molecular Weight ◽

Maldi Tof Ms ◽

Lung Cancer Patients ◽

Low Molecular Weight Proteins ◽

Tof Ms ◽

Proteins And Peptides

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Lung cancer risk stratification using methylation profile in the oral epithelium

Asian Cardiovascular and Thoracic Annals ◽

10.1177/0218492318813443 ◽

2018 ◽

Vol 27 (2) ◽

pp. 87-92 ◽

Cited By ~ 1

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.

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Association of FOXO3 Blood DNA Methylation with Cancer Risk, Cancer Survival, and Mortality

Cells ◽

10.3390/cells10123384 ◽

2021 ◽

Vol 10 (12) ◽

pp. 3384

Author(s):

Chenglong Yu ◽

Allison M. Hodge ◽

Ee Ming Wong ◽

Jihoon Eric Joo ◽

Enes Makalic ◽

...

Keyword(s):

Lung Cancer ◽

Dna Methylation ◽

Cancer Risk ◽

Cancer Survival ◽

Conditional Logistic Regression ◽

B Cell Lymphoma ◽

Case Control ◽

Case Control Studies ◽

Cox Models ◽

Total N

Genetic variants in FOXO3 are associated with longevity. Here, we assessed whether blood DNA methylation at FOXO3 was associated with cancer risk, survival, and mortality. We used data from eight prospective case–control studies of breast (n = 409 cases), colorectal (n = 835), gastric (n = 170), kidney (n = 143), lung (n = 332), prostate (n = 869), and urothelial (n = 428) cancer and B-cell lymphoma (n = 438). Case–control pairs were matched on age, sex, country of birth, and smoking (lung cancer study). Conditional logistic regression was used to assess associations between cancer risk and methylation at 45 CpGs of FOXO3 included on the HumanMethylation450 assay. Mixed-effects Cox models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for associations with cancer survival (total n = 2286 deaths). Additionally, using data from 1088 older participants, we assessed associations of FOXO3 methylation with overall and cause-specific mortality (n = 354 deaths). Methylation at a CpG in the first exon region of FOXO3 (6:108882981) was associated with gastric cancer survival (HR = 2.39, 95% CI: 1.60–3.56, p = 1.9 × 10−5). Methylation at three CpGs in TSS1500 and gene body was associated with lung cancer survival (p < 6.1 × 10−5). We found no evidence of associations of FOXO3 methylation with cancer risk and mortality. Our findings may contribute to understanding the implication of FOXO3 in longevity.

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