Adverse Health Effects of Betel Quid and the Risk of Oral and Pharyngeal Cancers

Abstract

Global reports estimate 600 million betel quid (BQ) chewers. BQ chewing has been demonstrated not only to be a risk factor for cancers of the oral cavity and pharynx and oral potentially malignant disorders (OPMD) but also to cause other cancers and adverse health effects. Herein, we summarized the international comparison data to aid in the understanding of the close relationship between the prevalence of BQ chewing, the occurrence of oral and pharyngeal cancers, and adverse health effects. Potential biomarkers of BQ carcinogens, such as areca nut, alkaloids, and 3-methylnitrosaminopropionitrile (MNPN), are closely associated with human health toxicology. Molecular mechanisms or pathways involving autophagy, hypoxia, COX-2, NF-κB activity, and stemness are known to be induced by BQ ingredients and are very closely related to the carcinogenesis of cancers of oral and pharynx. BQ abuse-related monoamine oxidase (MAO) gene was associated with the occurrence and progress of oral and pharyngeal cancers. In summary, our review article provides important insights into the potential roles of environmental BQ (specific alkaloid biomarkers and nitrosamine products MNPN) and genetic factors (MAO) and offers a basis for studies aiming to reduce or eliminate BQ-related OPMD and oral/pharyngeal cancer incidences in the future.

Figure 1

The long-term trend of incidence and mortality (ASRW) due to oral and pharyngeal cancers among males (per 100,000 population) and areca nut consumption (kg) of per person (population of 15 years) per year in Taiwan.

Figure 2

Chemical structure of major areca alkaloids [15].

Figure 3

Arecoline can be formed as AN-specific nitrosamine substances (areca-specific N-nitrosamines) by nitrosation reaction in the human body [16].

Figure 4

Major BQ alkaloids (arecoline) and major tobacco alkaloids (nicotine) can form nitrosamine substances by nitrosation reaction [17].