Polycyclic aromatic hydrocarbons as potential risk factors for thyroid cancer: Epidemiological evidence of urinary metabolites and thyroid-related hormones

Thyroid cancer (TC) is a common malignant tumor of the endocrine system, with a markedly higher incidence in females. While radiation exposure remains the only proven exogenous risk factor, growing evidence implicates environmental pollutants in TC pathogenesis. Polycyclic aromatic hydrocarbons (PAHs) are endocrine-disrupting chemicals with well-established carcinogenicity. However, epidemiological studies linking PAH exposure to TC risk are still insufficient. In this study, 116 patients with TC and 132 healthy adults were recruited in Guangdong Province, China, to assess the association between urinary concentrations of hydroxylated PAHs (OH-PAHs), thyroid-related hormone levels, and the risk of TC. The results identified 1-hydroxynaphthalene (1-OHN) and 2-hydroxynaphthalene (2-OHN) as dominant metabolites, with cases exhibiting significantly elevated 2 + 3-hydroxyfluorene (2 +3-OHF), 2 + 3-hydroxyphenanthrene (2 +3-OHPhe), 1 + 9-OHPhe, and 1-hydroxypyrene (1-OHP) concentrations, while controls showed higher 4-OHPhe levels. Quantile-based g-computation and Bayesian kernel machine regression models demonstrated a positive association between mixed exposure to OH-PAHs and both TC risk and serum free triiodothyronine (FT3) levels, with 2-OHN demonstrating primary contribution. FT3 and FT4 did not mediate the relationship between individual OH-PAH exposures and TC risk. Sex-stratified analysis revealed heightened female susceptibility even at low exposure levels. In the future, there is a need for more epidemiological and toxicological studies to investigate the causal and potential mechanisms underlying PAH exposure and TC risk.