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.

Background: Infertility history may have important implications for clinical practice and scientific discovery. Previous research on the validity of self-reported infertility measurements has been limited in scope and duration (< 5 years). In this study, we validated self-reported infertility history measures 15–23 years after fertility treatment initiation among women who utilized assisted reproductive technology (ART). Methods: Women who received ART treatments from three Boston infertility clinics and who enrolled in a prior study (1994–2003) were re-contacted in 2018 for the AfteR Treatment Follow-up Study (ART-FS). Infertility history was collected from clinical records and two self-report questionnaires (at ART initiation and at ART-FS enrollment). Treatment history included specific details (fresh or frozen embryo transfers, number of cycles) and treatment recall prior to ART initiation. Self-reported infertility diagnoses included polycystic ovary syndrome (PCOS), endometriosis, uterine factor infertility, tubal factor infertility, diminished ovarian reserve/advanced maternal age, male factor infertility, and other/unknown. We compared self-reported measures from 2018 to self-reported and clinical data from prior study initiation, using Cohen’s kappa, sensitivity, specificity, and 95% confidence intervals. Results: Of 2644 women we attempted to recontact, 808 completed the ART-FS, with an average follow-up of 19.6 years (standard deviation: 2.7). Recall of fertility treatment usage had moderate sensitivity (IVF = 0.85, Clomiphene/Gonadotropin = 0.81) but low specificity across different infertility treatment modalities (IVF = 0.63, Clomiphene/Gonadotropin = 0.55). Specific IVF details had low to moderate validity and reliability with clinical records. Reliability of recalled infertility diagnosis was higher when compared to self-report at ART initiation (PCOS K = 0.66, Endometriosis K = 0.76, Tubal K = 0.73) than when compared to clinical records (PCOS K = 0.31, Endometriosis K = 0.48, Tubal K = 0.62) and varied by diagnosis. Conclusions: The ability of women to recall specific IVF treatment details was moderately accurate and recall of self-reported infertility diagnosis varied by diagnosis and measurement method.

Background: Evidence from previous studies suggests that women firefighters have greater risk of some adverse reproductive outcomes. The purpose of this study was to investigate whether women firefighters had greater risk of miscarriage compared to non-firefighters and whether there were occupational factors associated with risk of miscarriage among firefighters. Methods: We studied pregnancies in the United States fire service using data from the Health and Wellness of Women Firefighters Study (n = 3181). We compared the prevalence of miscarriage among firefighters to published rates among non-firefighters using age-standardized prevalence ratios. We used generalized estimating equations to estimate relative risks (RRs) and 95% confidence intervals (CIs) between occupational factors (employment (career/volunteer), wildland firefighter status (wildland or wildland-urban-interface/structural), shift schedule, fire/rescue calls at pregnancy start) and risk of miscarriage, adjusted for age at pregnancy, education, gravidity, BMI, and smoking. We evaluated if associations varied by age at pregnancy or employment. Results: Among 1074 firefighters and 1864 total pregnancies, 404 pregnancies resulted in miscarriages (22%). Among most recent pregnancies, 138 resulted in miscarriage (13%). Compared to a study of US nurses, firefighters had 2.33 times greater age-standardized prevalence of miscarriage (95% CI 1.96–2.75). Overall, we observed that volunteer firefighters had an increased risk of miscarriage which varied by wildland status (interaction p-value< 0.01). Among structural firefighters, volunteer firefighters had 1.42 times the risk of miscarriage (95% CI 1.11–1.80) compared to career firefighters. Among wildland/wildland-urban-interface firefighters, volunteer firefighters had 2.53 times the risk of miscarriage (95% CI 1.35–4.78) compared to career firefighters. Conclusions: Age-standardized miscarriage prevalence among firefighters may be greater than non-firefighters and there may be variation in risk of miscarriage by fire service role. Further research is needed to clarify these associations to inform policy and decision-making.

The occupation of firefighting is classified as a Group 1 carcinogen. Increased cancer risk among firefighters may be partly attributable to increased occupational exposure to a range of chemicals, including per- and polyfluoroalkyl substances (PFAS). Some PFAS are known and suspect human carcinogens. Investigating epigenetic response to these PFAS exposures in firefighters may help to identify biological pathways of specific cancers, and previously unidentified health outcomes that are associated with PFAS. We therefore investigated the associations of serum PFAS concentrations with miRNA expression in firefighters. Serum samples collected from 303 firefighters from 6 sites across the USA were analyzed for 9 PFAS along with miRNA expression. Covariate-adjusted linear regression was used to estimate associations between log PFAS and miRNA expression, with false discovery rate (FDR) set to 0.05 for significance, and an exploratory cutoff of FDR q < 0.20. Gene set enrichment analysis (GSEA) was performed using miRTarBase's miRWalk pathways. Age, race-ethnicity, BMI, fire department, and sex were controlled for in all models. At FDR<0.05, the linear isomer of perfluorooctane sulfonic acid (PFOS) was inversely associated with miR-128-1-5p expression (Beta = -0.146, 95 % CI -0.216, -0.076). At a relaxed FDR of 0.20, we observed inverse associations for the sum of branched isomers of PFOS (Sm-PFOS) with 5 miRNAs (let-7d-5p, let-7a-5p, miR-423-5p, let-7b-5p, miR-629-5p). Several pathways were enriched for multiple PFAS, including those correlated with certain cancers, blood diseases, thyroid disorders, autoimmune disorders, and neurological outcomes. Some PFAS in firefighters were found to be associated with alteration of miRNA consistent with increased risk for a range of chronic diseases.

Objective: The aim of the study is to examine associations between years of firefighting service and eight chronological age-adjusted measures of blood leukocyte epigenetic age acceleration: Horvath, Hannum, SkinBloodClock, Intrinsic, Extrinsic, PhenoAge, GrimAge, and DNAm telomere length. Methods: The study used a repeated measures analysis of data from 379 incumbent firefighters from eight career departments and 100 recruit firefighters from two of the departments, across the United States. Results: Incumbent firefighters had on average greater epigenetic age acceleration compared with recruit firefighters, potentially due to the cumulative effect of occupational exposures. However, among incumbent firefighters, additional years of service were associated with epigenetic age deceleration, particularly for GrimAge, a strong predictor of mortality. Conclusions: Long-term studies with more specific occupational exposure classification are needed to better understand the relationship between years of service and aging biomarkers.