Firefighters found increased DNA methylation in a prostate cancer-associated region of the genome
American scientists evaluated the association between firefighting occupation, serum perfluoroalkyl compounds (PFAS) levels, and DNA methylation. The researchers found that firefighting experience was associated with DNA methylation at a locus responsible for an increased risk of prostate cancer. However, there is no meaningful evidence yet that these findings are specifically related to PFAS exposure and meaningfully affect the clinical progression of the disease at all. The work is published in the journal Environmental and Molecular Mutagenesis.
Firefighters are at increased risk of developing cancer due to occupational exposure to toxicants. The International Agency for Research on Cancer (IARC) categorizes the work of firefighters as a risk factor of the first category of carcinogenicity. One of the types of tumors that most commonly affect firefighters is considered to be prostate cancer, with a meta-analysis showing that firefighters have a risk ratio of 1.21 compared to the general population. One mechanism that may increase the risk of cancer for firefighters is epigenetic changes, the main one considered to be DNA methylation, in which a methyl group is added to a cytosine nucleotide by the enzyme DNA methyltransferase.
Epigenetic changes are considered to be one of the key mechanisms by which carcinogens exhibit their effects. Fire suppression is known to be associated with changes in DNA methylation and microRNA expression. However, there is no information on the extent to which DNA methylation after fire suppression affects loci associated with a particular type of cancer, nor on the extent to which the degree of methylation depends on the serum concentration of PFASs released during the burning process.
A team of scientists led by Jaclyn Goodrich of the University of Michigan investigated the association of fire suppression in general and PFAS exposure in particular with DNA methylation in regions of the genome that are associated with prostate cancer risk or severity. The analysis included 444 firefighters, some of whom had been firefighters for a long time and now work as trainers. The average age of an active firefighter was 41 years, of which 15 years were spent working as a firefighter.
Researchers examined DNA methylation at 2,600 CpG sites in chromosome 8q24 and GSTP1, home to genes associated with prostate cancer development and progression, and found 15 sites that were significantly associated with current firefighter status in adjusted models, including eight sites in regions encoding genes. In statistical models of firefighter experience, years of firefighting were significantly associated with only one CpG island in the Alu repeat region (p = 0.025).
Of the nine PFASs analyzed, only exposure to branched PFAS isomers was associated with differential methylation at any of the CpG sites tested. Among the 182 participants who had Alu repeat methylation data, no PFAS was significantly associated with Alu repeat methylation. This was unaffected by the fact that active firefighters were found to have elevated serum concentrations of perfluoromethylheptanesulfonate isomers.
The scientists do not yet know if these results will be replicated in other firefighter populations. If the results can be replicated with another group, the Goodrich team will be well positioned to propose biological hypotheses to explain the complex interactions between occupational exposure to firefighters and PFAS and the development of prostate cancer.