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

试点项目 I：对槟榔咀嚼者口腔细胞和毛发中的槟榔生物碱进行横断面分析，作为短期和长期槟榔暴露的候选生物标志物

• 批准号: 10265528
• 负责人: ANA JOY MENDEZ
• 金额: $ 6.25万
• 依托单位: UNIVERSITY OF GUAM
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-01 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10265528
• 关键词: 12 year old; 18 year old; Address; Adult; Air; Algorithms; Alkaloids; Areca; Arecoline; Behavior; Biological Markers; Calendar; Cells; Cheek structure; Child; Consumption; Country; Cross-Sectional Studies; Data; Detection; Distal; Ethnic Origin; Frequencies; Growth; Guam; Habits; Hair; High Prevalence; Human; Incidence; Length; Limes; Malignant Neoplasms; Mass Spectrum Analysis; Mastication; Measures; Minority; Nuts; Oral cavity; Oral mucous membrane structure; Pacific Island Americans; Pacific Islands; Patient Self-Report; Pilot Projects; Plant Leaves; Prevalence; Questionnaires; Reporting; Risk Factors; Scalp structure; Specimen; Techniques; Time; Tobacco; Work; absorption; candidate marker; health disparity; health equity; innovation; junior high school; malignant mouth neoplasm; novel; success; trend; underserved minority

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.

项目摘要 槟榔咀嚼是一种上瘾的致癌行为， 世界各地的人们。这些咀嚼AN的人大多是居住在非洲国家的得不到充分服务的少数民族。 包括关岛在内的西太平洋地区。因此，迫切需要AN停止试验来解决这个问题 严重的健康差距问题。然而，迫切需要客观的生物标志物来验证短期和短期的生物标志物。 目前还没有用于此类试验的长期AN暴露。应用创新的质量 光谱技术，我们建议首次建立可靠的生物标志物，以客观地 测量短期和长期的AN暴露。这些生物标志物可用于评估咀嚼状态 并客观地确定AN戒烟试验中的依从性和有效性。正如我们和其他人所发现的， 槟榔生物碱槟榔碱、槟榔定、古伐克林和古伐辛对AN是特异性的。因此这些 如果能够在人体样本中检测到生物碱，则生物碱可以作为AN暴露的可靠生物标志物 咀嚼后。颊细胞（BC）和头皮毛发可以非侵入性地收集，并提供广泛的 根据长度，几天（BC）和几个月（头发）的AN暴露日历。在这 在这项研究中，我们将使用一种创新的方法， AN咀嚼者的头发自我报告短期（前一周）和长期（前一个月或六个月） 月前）使用经验证的AN问卷进行AN暴露。作为一个新的概念，我们将表达一个 将咀嚼者的AN暴露作为其“平均AN负荷”（“AANL”）。使用来自AN问卷的数据，我们 我将通过每次咀嚼的AN量乘以平均值来计算咀嚼者的AANL 咀嚼时间和平均每日咀嚼频率，并考虑到AN 留在嘴里。作为一个额外的新奇，我们将利用咀嚼者的AANL为前一周， 上个月和六个月前生成的算法，回顾性地近似AN 暴露于测量的生物碱水平。这些算法将分别为两个主要的 关岛的咀嚼者类型：那些单独咀嚼AN的人（“1类咀嚼者”）和那些咀嚼AN作为 一种槟榔块，由硝酸铵作为主要成分，包裹在槟榔叶中，加入熟石灰， 烟草（第2类咀嚼类）。AN戒烟试验是减少AN诱发的最有效方法 癌的然而，这些试验迫切需要可靠的生物标志物来确定短期和长期试验 合规我们的工作旨在建立这样的生物标志物。这将有助于全面成功 全球范围内的AN戒烟试验，从而降低全球AN患病率 咀嚼及其相关的健康差异，特别是口腔癌。