DNA methylation among firefighters

Firefighters are exposed to carcinogens and have elevated cancer rates. We hypothesized that occupational exposures in firefighters would lead to DNA methylation changes associated with activation of cancer pathways and increased cancer risk. To address this hypothesis, we collected peripheral blood...

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Bibliographic Details
Published in:PloS one 2019-03, Vol.14 (3), p.e0214282
Main Authors: Zhou, Jin, Jenkins, Timothy G, Jung, Alesia M, Jeong, Kyoung Sook, Zhai, Jing, Jacobs, Elizabeth T, Griffin, Stephanie C, Dearmon-Moore, Devi, Littau, Sally R, Peate, Wayne F, Ellis, Nathan A, Lance, Peter, Chen, Yin, Burgess, Jefferey L
Format: Article
Language:English
Subjects:
Adult
AMP
AMP-activated protein kinase
Analysis
Biology and life sciences
Breast cancer
California
Cancer
Cancer patients
Carcinogens
CpG Islands
Deoxyribonucleic acid
DNA
DNA Methylation
DNA probes
EDTA
Epidemiology
Epigenetics
Firefighters
Fires
Gene expression
Gene Regulatory Networks - genetics
Genes
Genome, Human
Genomes
Genomics
Health aspects
Health maintenance organizations
Health risks
Humans
Kinases
Lung cancer
Male
Medicine and Health Sciences
Methylation
MicroRNAs
Middle Aged
Minority & ethnic groups
Mortality
Neoplasms - genetics
Neoplasms - pathology
Non-Smokers
Occupational Exposure
p53 Protein
People and Places
Peripheral blood
Physical Sciences
Polycyclic aromatic hydrocarbons
Predictions
Protein kinases
Proteins
Public health
Signal transduction
Signal Transduction - genetics
Signaling
Smoking
Statistical analysis
Statistical methods
Studies
Supervision
Tumor proteins
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Description
Summary:Firefighters are exposed to carcinogens and have elevated cancer rates. We hypothesized that occupational exposures in firefighters would lead to DNA methylation changes associated with activation of cancer pathways and increased cancer risk. To address this hypothesis, we collected peripheral blood samples from 45 incumbent and 41 new recruit non-smoking male firefighters and analyzed the samples for DNA methylation using an Illumina Methylation EPIC 850k chip. Adjusting for age and ethnicity, we performed: 1) genome-wide differential methylation analysis; 2) genome-wide prediction for firefighter status (incumbent or new recruit) and years of service; and 3) Ingenuity Pathway Analysis (IPA). Four CpGs, including three in the YIPF6, MPST, and PCED1B genes, demonstrated above 1.5-fold statistically significant differential methylation after Bonferroni correction. Genome-wide methylation predicted with high accuracy incumbent and new recruit status as well as years of service among incumbent firefighters. Using IPA, the top pathways with more than 5 gene members annotated from differentially methylated probes included Sirtuin signaling pathway, p53 signaling, and 5' AMP-activated protein kinase (AMPK) signaling. These DNA methylation findings suggest potential cellular mechanisms associated with increased cancer risk in firefighters.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0214282