Exposome, Ultrafine Particles, and Glioblastoma: A New Perspective

Glioblastomas (GBM) are the most common primary brain tumors in adults, but their causes remain largely unknown. Environmental exposures are suspected to play a role; however, the data is limited due to analytical challenges and the difficulty of obtaining brain samples for cohort studies. This study investigates the chemical exposome in GBM, with a focus on an underexplored source: Ultrafine particles (UFPs), the smallest component of air particulate matter. UFPs are known to penetrate the brain and transport hazardous substances, and previous epidemiological studies suggest a potential link between ambient air UFPs and disease incidence. This study leveraged the Bellvitge Glioma Cohort (BGC) from HUB-IDIBELL, a unique retrospective cohort of 400 patients with high-quality histopathology brain tumor samples collected from 2005 to present. Additionally, non-tumor brain samples from autopsies were analyzed. In this proof-of-concept study, 33 GBM samples and 20 non-tumoral brain samples were examined using a comprehensive HRMS-based wide-scope target and nontarget analysis. We also analyzed 20 UFP samples from the metropolitan area of Barcelona, where cohort patients lived. A total of 49 exogenous chemicals, including various industrial compounds, were identified. While chemical profiles in GBM differed significantly from those in healthy brain tissue, no direct link to disease onset could be established. However, the results underscore the need for thorough assessments of potential chemical contributions to GBM. Notably, several air pollutants linked to road traffic, such as tire additives, were detected, supporting the hypothesis that hazardous chemicals may access the brain via the olfactory pathway. Our UFP analysis from the Barcelona area revealed over 20,000 features, including chemicals previously identified in the brain (e.g., tire additives), further substantiating this hypothesis.