Abstract Areca nut (AN) is classified as a Group 1 carcinogen by the International Agency for Research on Cancer (IARC). It is a widely consumed psychoactive substance with profound cultural roots in regions including Hunan, Hainan, and Taiwan of China. Its key bioactive components include alkaloids (e.g. arecoline and arecaidine) and areca nut-specific nitrosamines (NSAs), that induce DNA damage, reactive oxygen species (ROS) bursts, and chronic inflammation in oral tissues. Coupled with mechanical trauma from chewing, these insults drive the malignant progression of oral submucous fibrosis (OSF) to oral cavity carcinomas (OCCs). This review systematically outlines the pathological progression from normal oral mucosa to invasive OCCs, highlighting two core mediators of OSF carcinogenesis: immune microenvironment reprogramming and oncogenic signaling activation. Furthermore, this review elaborates the molecular mechanisms of areca nut-induced oral cancer, providing a theoretical foundation for biomarker discovery and the development of novel therapeutic strategies. It also provides actionable guidance for reducing the incidence of areca nut-related OCCs and improving patient prognosis.
Yu et al. (Wed,) studied this question.