Study finds a possible biomarker of occupational exposure in firefighters
By Ashley Godfrey
NIEHS grantee Shuk-mei Ho, Ph.D., (http://www.eh.uc.edu/dir_individual_details.asp?qcontactid=702) professor and chair of environmental health at the University of Cincinnati (UC) and colleagues have found an epigenetic change, a modification of a gene that is independent of any change in the gene sequence itself, which can distinguish firefighters from non-firefighters.
Their NIEHS-funded study (http://www.ncbi.nlm.nih.gov/pubmed/22796920) suggests there is a link between exposures to smoke, which contains a mixture of pollutants including polycyclic aromatic hydrocarbons (PAHs), and an epigenetic mark of promoter methylation, the addition of a methyl group to the area that controls gene expression. PAHs are one of the many chemicals found in smoke and products of incomplete combustion, and firefighters are often exposed to this complex mixture of toxicants when fighting fire.
“This work was inspired by the fact that exposure science can now look at the physiological changes caused by a complex mixture of chemicals, and it serves as a proof-of-concept study that this approach can work,” stated Ho.
Understanding the link between exposure and future health risks
According to Ho, one of the motivations for this study came from results published by one of her colleagues at UC, NIEHS grantee Grace LeMasters, Ph.D. (http://www.eh.uc.edu/dir_individual_details.asp?qcontactid=35) LeMasters had completed a large study combining data from 32 different published reports and found that firefighters are at a higher risk for developing a number of different cancers. Ho wanted to investigate why firefighters are at increased risk by looking for a link between their risk of exposure and epigenetic changes in their genome, which emerging evidence suggests are relevant to disease development.
Ho and her large multidisciplinary team considered four different genes that had been reported to be associated with environmental exposures to traffic-related PAHs in an asthma study of children living in traffic-dense areas in an NIEHS-funded collaborative study with Frederica Perara, Ph.D., (http://www.mailman.columbia.edu/our-faculty/profile?uni=fpp1) (see story). The promoter methylation status of one of the genes (ACSL3) was validated to be associated with PAH-induced asthma but the other candidates have not been fully investigated.
In the current firefighter study, her research team showed one of these previously not studied candidates, DUSP22, could distinguish between firefighters and non-firefighters.
The study also showed that this mark was associated with years in service because the extent of methylation correlated with the duration of firefighting service and not with age.
“This mark is almost like a memory of how long they have been in service,” said Ho.
She further explained that because epigenetic changes are passed to the next generation of cells over time, the changes could become a signature and a way of measuring both the duration and extent of exposure.
Implications for the field of environmental research
One of the possibilities raised by this study is that environmental exposure can induce epigenetic changes that will last for a long time and could serve as a biomarker for exposure. Combined with other biomarkers, these signatures can help public health professionals better understand the impact of a complex environmental exposure. Ho is hopeful that in the future, measuring this type of exposure related epigenetic marks could help to predict or associate an individual’s risk of developing cancer, or other diseases, in later life.
There are also a number of interesting questions that Ho would like to answer in some of her future studies. One is how long the methylation mark persists after the firefighters stop working and are no longer at risk of being exposed to the toxicants on a regular basis.
Another important public health question is whether an intervention strategy would be able to reverse the changes. Ho believes the answers could lay groundwork for future surveillance and intervention strategies. Ho also suggests the broader implications for this research are important, especially in light of this summer’s wildfire outbreaks.
“Conceptually it might be possible to find epigenetic changes in residents living in wildfire areas and see who has been exposed and for how long,” explained Ho.
She is also interested in expanding this type of research to other types of exposures related to the intense or incomplete combustion of fossil fuels, such as exposures experienced by individuals living in traffic laden cities or oil rig workers and oil spill clean up crews.
Citations: Ouyang B, Baxter CS, Lam HM, Yeramaneni S, Levin L, Haynes E, Ho SM. (http://www.ncbi.nlm.nih.gov/pubmed/22796920) 2012. Hypomethylation of Dual Specificity Phosphatase 22 Promoter Correlates With Duration of Service in Firefighters and Is Inducible by Low-Dose Benzo[a]Pyrene. J Occup Environ Med 54(7):774-80.
Perera F, Tang WY, Herbstman J, Tang D, Levin L, Miller R, Ho SM. (http://www.ncbi.nlm.nih.gov/pubmed/19221603?ordinalpos=3&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum) 2009. Relation of DNA methylation of 5'-CpG island of ACSL3 to transplacental exposure to airborne polycyclic aromatic hydrocarbons and childhood asthma. PLoS ONE 4(2):e4488. doi:10.1371/journal.pone.0004488. Summary
(Ashley Godfrey, Ph.D. is a postdoctoral fellow in the Molecular and Genetic Epidemiology Group in the NIEHS Laboratory of Molecular Carcinogenesis.)