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: 10084114
• 负责人: Adrian A Franke
• 金额: $ 8.77万
• 依托单位: UNIVERSITY OF HAWAII AT MANOA
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-28 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10084114
• 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（An）咀嚼是一种额外的引起癌症的行为，数亿美元 全球人。大多数人都在居住在服务不足的国家中 西太平洋地区包括关岛。那迫切需要进行戒烟来解决这个问题 严重的健康差异问题。但是，迫切需要客观的生物标志物来验证简短和 目前尚不可用进行此类试验的长期接触。应用创新的群众 光谱技术，我们建议首次建立可靠的生物标志物以客观地建立 测量短期和长期暴露。这些生物标志物可用于评估咀嚼状态 并在戒烟试验中客观地确定合规性和效率。正如我们和其他人发现的那样 槟榔生物碱，跨甲胺，番茄和番石榴是特定于an的。那，这些 如果可以在人类标本中检测到生物标志物，则可以用作可靠的生物标志物 咀嚼后。颊细胞（BCS）和头皮头发可以无创收集，并提供宽阔的 暴露几天（BC）和几个月（头发）的日历，具体取决于长度。在这个 研究，我们将使用一种与BCS和头皮测量的槟榔生物碱水平相关的创新方法 咀嚼者的头发，要自我报告的短期（上周）和长期（上个月，六个 几个月前）使用验证的问卷进行曝光。作为一个新颖的概念，我们将表达 Chewer是“平均负载”（“ AANL”）的曝光。使用来自问卷的数据，我们 将通过将咀嚼量的每个会话乘以平均 咀嚼时间和平均每日咀嚼频率，并考虑到AN的时间 留在嘴里。作为额外的新颖性，我们将在上周利用厨师的AANL， 上个月，以及生成算法之前的六个月，回顾性地近似 从测得的生物碱水平暴露。这些算法将分别为两个主生成 关岛的咀嚼类型：咀嚼一个人（“ 1级咀嚼”）和那些咀嚼的人 Betel quid由包裹在槟榔叶中的主要成分和蓝色石灰和 烟草（“ 2级咀嚼”）。戒烟试验是减少AN引起的最有效方法 癌症。但是，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 遵守。我们提出的工作旨在建立此类生物标志物。这将有助于整体成功 全世界的戒烟试验，从而降低了全球流行率 咀嚼及其相关的健康差异，尤其是口腔癌。