Detection of cancer epigenetic alterations in a pilot cohort of workers exposed to TiO2.

Abstract

Introduction: The extensive use of TiO₂ for several applications poses the problem of its safety. Notably, TiO₂ has been classified as type Group 2 B carcinogen by IARC in 2010. It is widely known that DNA methylation is influenced by the exposure to environmental triggers, including occupational risk factors. The aim of this study was to evaluate the presence of a cancer DNA methylation alteration in TiO₂ exposed workers from a TiO₂ powder production plant.

Methods: Due to the possible entry route, by ingestion or by inhalation, of TiO₂ nanoparticles in the workers of our study cohort, we analysed a DNA methylation biomarker altered in lung and colorectal cancers. The analysis was conducted by MethyLight expressing DNA methylation values as Ct (lower Ct indicates higher methylation level and viceversa), in cfDNA from plasma samples comparing workers with different duties from a plant producing TiO₂ pigment powder, unexposed subjects as healthy controls and colorectal cancer patients as positive controls, also considering job-related variables.

Results: The obtained results showed that exposed workers displayed higher methylation compared to healthy controls approaching the methylation patterns of colorectal cancer patients, even more evident for workers of some job categories. Moreover, the methylation data would highlight the importance of personal protective equipment, as observed in workers using a gas mask exhibiting a negligible methylation value compared to the job category average methylation level.

Discussion: This preliminary investigation suggests the harmful role of TiO₂ in altering DNA methylation patterns potentially leading to tumorigenesis and highlights the importance of monitoring workers exposed to TiO₂ particles.