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. 2024 Jan-Feb;65(1-2):55-66.
doi: 10.1002/em.22589. Epub 2024 Mar 24.

Firefighting, per- and polyfluoroalkyl substances, and DNA methylation of genes associated with prostate cancer risk

Margaret Quaid  1 , Jaclyn M Goodrich  1 , Miriam M Calkins  2 , Judith M Graber  3 , Derek Urwin  4   5 , Jamie Gabriel  4 , Alberto J Caban-Martinez  6 , Rebekah L Petroff  1 , Casey Grant  7 , Shawn C Beitel  8 , Sally Littau  8 , John J Gulotta  9 , Darin Wallentine  9 , Jeff Hughes  10 , Jefferey L Burgess  7
Affiliations

Firefighting, per- and polyfluoroalkyl substances, and DNA methylation of genes associated with prostate cancer risk

Margaret Quaid et al. Environ Mol Mutagen. 2024 Jan-Feb.

Abstract

Prostate cancer is the leading incident cancer among men in the United States. Firefighters are diagnosed with this disease at a rate 1.21 times higher than the average population. This increased risk may result from occupational exposures to many toxicants, including per- and polyfluoroalkyl substances (PFAS). This study assessed the association between firefighting as an occupation in general or PFAS serum levels, with DNA methylation. Only genomic regions previously linked to prostate cancer risk were selected for analysis: GSTP1, Alu repetitive elements, and the 8q24 chromosomal region. There were 444 male firefighters included in this study, with some analyses being conducted on fewer participants due to missingness. Statistical models were used to test associations between exposures and DNA methylation at CpG sites in the selected genomic regions. Exposure variables included proxies of cumulative firefighting exposures (incumbent versus academy status and years of firefighting experience) and biomarkers of PFAS exposures (serum concentrations of 9 PFAS). Proxies of cumulative exposures were associated with DNA methylation at 15 CpG sites and one region located within FAM83A (q-value <0.1). SbPFOA was associated with 19 CpG sites (q < 0.1), but due to low detection rates, this PFAS was modeled as detected versus not detected in serum. Overall, there is evidence that firefighting experience is associated with differential DNA methylation in prostate cancer risk loci, but this study did not find evidence that these differences are due to PFAS exposures specifically.

Keywords: DNA methylation; environmental exposures; epigenetics; firefighting; occupational health.

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Conflict of interest statement

CONFLICTS OF INTEREST

We have no conflicts of interest to disclose.

Figures

Figure 1.
Figure 1.
Participants Included in the Study. This is an on-going study with more than 4,000 participants currently enrolled in FFCCS, of whom 658 had available epigenetic analyses. 444 participants met the requirements of the study and had data available to model firefighting experience relative to methylation of chromosome 8q24 and GSTP1, 324 of which were also available for Alu analysis. 291 of the 444 total participants also had quantified PFAS serum levels and thus could be included in models which describe the relationship between PFAS serum level and DNA methylation at chromosome 8q24 and GSTP1. 182 were available for Alu pyrosequencing and could be used to model the relationship between PFAS serum levels and Alu methylation.
Figure 2.
Figure 2.
FAM83A Average DNA Methylation by Incumbent Status. Unadjusted average methylation of the statistically significant DMR, stratified by incumbent status. This region covers the transcription start site or the first exon, depending on the transcript variant (Nassar et al., 2023). The arrow signifies the transcription start site.
See this image and copyright information in PMC

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