Gliomas are aggressive brain tumors with high morbidity and mortality rates. Scientists have conducted extensive research to identify environmental and genetic risk factors. Research shows that ionizing radiation and air pollution have established links, but the effects of other environmental factors remain inconclusive. Data from The Cancer Genome Atlas (TCGA) and Glioma Longitudinal Analysis (GLASS) databases showed mutational signatures that stemmed from aging processes and environmental exposures, specifically haloalkanes. This study further validated previous findings by evaluating gliomas from individuals who worked as professional firefighters because this occupation leads firefighters to encounter haloalkanes in flame retardant and fire extinguishing materials.
Tumor DNA analysis of 17 firefighters and 18 non-firefighters diagnosed with glioma examined the link between firefighting work and glioma-related mutational signatures. The research team obtained participants through the University of California, San Francisco (UCSF) Adult Glioma Study (AGS), conducted between 1991 and 2013. Each participant provided tumor and blood specimens while receiving neuropathological testing, followed by an occupational history interview.
Whole-exome sequencing analysis of blood DNA and tumor DNA sequences took place at the Yale Center for Genomic Analysis. The IDT xGen formalin-fixed paraffin-embedded DNA library Prep Kit served to generate Next-generation sequencing libraries, which were sequenced on an Illumina NovaSeq S4 platform. Statistically insignificant mutations and common variants were filtered out through data analysis tools such as cancer-effectsizeR and MutationalPatterns packages. The research examined the presence of mutational signature SBS42 in glioma samples, which represents haloalkane exposure associations.
The analysis of 35 glioma samples revealed that 13 of them displayed SBS42-induced variants at the median level. Research participants who worked as firefighters accumulated an average of 22 years of exposure before receiving their glioma diagnosis seven years after their last exposure to firefighting conditions. High-grade gliomas, along with wild-type IDH1/IDH2 mutations, were found in most tumors examined. Chemotherapy, together with radiation therapy, used to be the standard procedure before collecting blood samples.
Data showed a positive correlation between firefighting duration and SBS42 variant classification (p = 0.04, R² = 0.29). The two firefighters with prominent SBS42 variant counts were also engaged in farming activities, practicing pesticide applications, and working in petroleum transport. The SBS42 signature elevation was found in both firefighting personnel and workers who conducted painting and did mechanical work, indicating widespread occupational exposure possibilities.
SBS42 variant counts over 10 detected particular oncogenic mutations in NOTCH1, ROS1, ETV1, and NCOA2, according to the COSMIC database. Based on these results, researchers have established that SBS42 functions as a driver of genetic transformations which cause glioma development in people exposed to the SBS42 signature.
Research findings indicate the SBS42 signature exists in brain tumors of firefighters, which supports assumptions about haloalkane products being gliomagenic agents. Gliomas primarily develop because of aging-related endogenous mutations, but some cases involve mutations from environmental exposures. Public health interventions need a foundation of occupational hazard identification to develop effective measures against cancer risks. Further research is required to establish exposure limits and protective measures that should be implemented for firefighters who face elevated cancer risks.
References: Cannataro VL, Bracci PM, Taylor JW, et al. Glioma mutational signatures associated with haloalkane exposure are enriched in firefighters. Cancer. Published online March 10, 2025. doi:10.1002/cncr.35732
