Occupational
Associations of per- and polyfluoroalkyl substances (PFAS) exposures and firefighting experience with microRNA signatures of papillary thyroid cancer Cynthia Porter* Cynthia Porter Porter Porter Porter Porter Porter Department of Epidemiology and Biostatistics, Mel and Enid Zuckerman College of Public Health, University of Arizona, Tucson, AZ, USA
Background: Papillary thyroid cancer (PTC) is the most commonly diagnosed thyroid cancer. Prior research shows that expression of specific circulating blood microRNAs (miRNAs) differs between individuals with PTC and those without disease, suggesting biomarker relevance. Firefighters may experience an elevated risk of developing PTC due to occupational exposures, including per- and polyfluoroalkyl substances (PFAS).
Methods: This study investigated associations between firefighter-related exposures (serum PFAS, years of firefighting experience, and incumbent versus recruit status) and PTC-relevant miRNA expression. MiRNA expression was quantified from blood collected from 833 firefighters across 15 sites, and 302 firefighters had nine PFAS analytes measured in serum. Thirty PTC-related miRNAs were identified using miRWalk’s Disease Ontology. Adjusted linear regression models estimated associations between exposures and miRNA expression while controlling for occupational and demographic covariates. Multiple comparisons were assessed using a False Discovery Rate (FDR) threshold of p < 0.20.
Results: Twenty statistically significant (p < 0.05) negative associations were observed between five serum PFAS analytes and 10 miRNAs. These included associations between Sb-PFOA and hsa-miR-212-3p; PFHxS and hsa-let-7a-5p, hsa-let-7d-5p, hsa-let-7f-5p; PFNA and hsa-let-7a-5p, hsa-let-7b-5p, hsa-let-7c-5p, and hsa-let-7d-5p; Sm-PFOS and hsa-let-7a-5p, hsa-let-7b-5p, hsa-let-7c-5p, hsa-let-7d-5p, hsa-let-7e-5p, and hsa-miR-760; and n-PFOS and hsa-let-7a-5p, hsa-let-7c-5p, hsa-let-7d-5p, hsa-let-7e-5p, and hsa-let-7f-5p. Twenty-four of 30 miRNAs were associated with incumbent status, and 22 remained significant after FDR correction. Hsa-miR-212-3p and let-7 family miRNAs were negatively associated with PFAS and incumbency.
Conclusion: Associations between PFAS exposure, firefighting status, and PTC-related miRNAs suggest links between occupational exposures and PTC risk overall.