Pilot Project I: Cross-Sectional Analysis of Areca Alkaloids in Buccal Cells and Hair from Areca Nut Chewers as Candidate Biomarkers for Short- and Long-Term Areca Nut Exposure

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PROJECT SUMMARY Areca nut (AN) chewing is an addictive cancer-causing behavior practiced by hundreds of millions of people worldwide. Most of these AN chewers are underserved minorities who reside in countries of the Western Pacific Region including in Guam. Thus, AN cessation trials are urgently needed to address this severe health disparity problem. However, critically required objective biomarkers to verify short- and long-term AN exposure for such trials are currently not available. Applying an innovative mass spectrometry technique, we propose to establish for the first time reliable biomarkers to objectively measure short- and long-term AN exposure. These biomarkers can be used to assess chewing status and objectively determine compliance and efficacy in AN cessation trials. As found by us and others, the areca alkaloids arecoline, arecaidine, guvacoline, and guvacine are specific to the AN. Thus, these alkaloids can serve as reliable biomarkers for AN exposure if they can be detected in human specimens after AN chewing. Buccal cells (BCs) and scalp hair can be non-invasively collected and provide a broad calendar of AN exposure of several days (BCs) and several months (hair) depending on length. In this study, we will use an innovative approach of correlating areca alkaloid levels measured in BCs and scalp hair of AN chewers to self-reported short-term (previous week) and long-term (previous month or six months prior) AN exposure using validated AN questionnaires. As a novel concept, we will express a chewer’s AN exposure as their "average AN load" (“AANL”). Using data from the AN questionnaires, we will calculate the chewer’s AANL by multiplying the amount of AN chewed per session by the average chewing time and the average daily chewing frequency and taking into consideration the time the AN is retained in the mouth. As an additional novelty, we will utilize the chewer’s AANL for the previous week, previous month, and six months prior to generate algorithms that retrospectively approximate AN exposure from measured alkaloid levels. These algorithms will be generated separately for the two main types of chewers in Guam: those who chew AN alone (‘class 1 chewers’) and those who chew AN as a betel quid consisting of AN as the primary ingredient wrapped in a betel leaf with slaked lime and tobacco (‘class 2 chewers’). AN cessation trials are the most effective approach to reduce AN-induced cancers. However, these trials urgently require reliable biomarkers to determine short- and long-term trial compliance. Our proposed work aims to establish such biomarkers. This will assist in the overall success of AN cessation trials worldwide and consequently in the reduction of the global prevalence of AN chewing and its associated health disparities, particularly oral cancer.