# 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

> **NIH NIH U54** · UNIVERSITY OF HAWAII AT MANOA · 2021 · $101,206

## Abstract

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.

## Key facts

- **NIH application ID:** 10266802
- **Project number:** 5U54CA143727-12
- **Recipient organization:** UNIVERSITY OF HAWAII AT MANOA
- **Principal Investigator:** Adrian A Franke
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $101,206
- **Award type:** 5
- **Project period:** 2009-09-28 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10266802

## Citation

> US National Institutes of Health, RePORTER application 10266802, 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 (5U54CA143727-12). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10266802. Licensed CC0.

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