Associations of exposure to arsenic species and endogenous sex hormones with oral cancer: a hospital-based study in Southeastern China

The effects of arsenic species and endogenous sex hormones on oral cancer risk, particularly their molecular interactions, have been infrequently reported. This study aimed to assess the individual and combined effects of arsenic species and endogenous sex hormones on oral cancer risk and elucidate the association between hormones, arsenic species, and arsenic metabolism. A case-control study (comprising 144 cases and 144 controls) was conducted from January 2020 to January 2024 in Southeastern China. Serum levels of six arsenic species and nine endogenous sex hormones were measured using High-Performance Liquid Chromatography Inductively Coupled Plasma Mass Spectrometry (HPLC-ICP-MS) and ultra-high performance liquid chromatography-high resolution mass spectrometry (UPLC-HRMS), respectively. After adjusting for potential confounders, Logistic regression showed that high exposure levels of inorganic arsenic (IAs) (adjusted OR [aOR] and 95 %CI: 0.00[0.00,0.44] and 0.45[0.25,0.78]) and Cortisone (aOR and 95 %CI: 0.16[0.07,0.35] and 0.19[0.10,0.37]) were associated with reduced oral cancer risk, both as continuous and categorical variables. Serum Melatonin, Cortisone, and Testosterone levels correlated with partial arsenic species, while Cortisone and Melatonin were linked to arsenic methylation metabolic indexes (spearman's test P < 0.05). Quantile g-computation analysis revealed that Corticosterone and Cortisone had the largest positive and negative weights on oral cancer risk, respectively (weights = 0.640 and 0.525). The combined effect of arsenic species and hormones on oral cancer was protective (β and 95 %CI: 0.36(-0.05,-0.67)), with slight gender differences. Independent of other arsenic species and hormone levels, Cortisone exhibited a protective effect against oral cancer in BKMR analysis. Additionally, an interaction effect between Melatonin and other arsenic species was also observed. In summary, Serum IAs and Cortisone were negatively associated with oral cancer, while Corticosterone showed a positive association. Further cohort studies are needed to confirm and elucidate these mechanisms.