Validation of PAH Biomarkers for Quantifying Cancer Risk

验证用于量化癌症风险的 PAH 生物标志物

• 批准号: 6522503
• 负责人: JUNFENG ZHANG
• 金额: $ 21.05万
• 依托单位: UNIV OF MED/DENT NJ-SCH OF PUBLIC HEALTH
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-30 至 2004-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6522503
• 关键词: China; Chinese; benzopyrenes; biomarker; cancer risk; carbopolycyclic compound; chemical carcinogen; clinical research; environmental exposure; environmental toxicology; human subject; neoplasm /cancer; neoplasm /cancer epidemiology; pyrenes; urinalysis; urine

DESCRIPTION (provided by applicant): Biological monitoring is particularly useful for assessing exposure to pollutants, such as polycyclic aromatic hydrocarbons (PAHs), that are present in multiple environmental media. Although a number of PAH biomarkers have been developed, epidemiological studies relating cancer mortality to average biomarker concentrations are lacking; and the current risk assessment frame is based on air concentrations of benzo[a]pyrene (BaP). The goal of the proposed study is to fill in several important gaps that have hampered the application of PAH biomarkers in quantifying cancer risk. Two urinary markers, 1-hydroxypyrene and 9-hydroxy-benzo[a]pyrene, will be specifically validated for this purpose through achieving the following specific aims. Aim 1 is to establish a quantitative relationship between urinary concentrations and BaP exposure which will be measured as 24-h average personal air concentration and 24-h dietary intake. Aim 2 is to examine whether there is a significant day-to-day variation in urinary marker concentrations in study subjects having stable daily PAH exposures. This is important because for a biomarker to be useful for estimating cancer risk, this marker should be able to predict people's average (steady) exposure. Aim 3 is to examine whether a first morning urine sample can efficiently represent daily exposure or a 24-hour composite urine sample is required. This is of practical importance because 24-h urine samples are considerably harder to get in free-living populations. Aim 4 is to examine relationships between urinary markers and other PAH metrics, because other metrics of PAH mixture may prove to be a better index for future risk assessment. The study will be carried out in 100 non-smoking adults with a wide range of exposure to airborne BaP, including both occupationally and non-occupationally exposed individuals. This is necessary to evaluate the effectiveness of these biomarkers in a broader application, because high PAH exposures can occur not only in many occupational settings but also in the daily lives of other people, including non-smokers. The study will consist of two sets of repeated measurements for each subject. Each set of the measurement will include: 24-h personal breathing-zone concentrations of gas-phase and particle-phase PAHs; 24-h dietary PAH intakes; biomarker concentrations in first morning urine and in 24-h composite urine. All these measurements will be made within the same 24-h period. Two repeated measurements will be separated by at least three months for each subject to maximize the representativeness of daily exposure. Air samples and food samples will be analyzed for at least 16 common PAHs including pyrene and BaP using the established HPLC/fluorescence methods. The spot nature of urinary concentrations will be corrected with creatinine. Statistical methods to be used will include descriptive analyses, scatter plots, correlation analyses, paired comparisons, and linear mixed models. In the mixed models, age, sex, height, weight, and body mass index will be adjusted for.

描述（由申请人提供）： 生物监测对于评估暴露特别有用 存在的污染物，例如存在的多环芳烃（PAHS） 在多个环境媒体中。虽然许多PAH生物标志物已经 开发的流行病学研究将癌症死亡与平均水平有关 缺乏生物标志物浓度；当前的风险评估框架是 基于苯并[a] pyrene（BAP）的空气浓度。提议的目标 研究是要填补几个妨碍申请的重要空白 PAH生物标志物在量化癌症风险方面。两个尿标记， 1-羟基苯乙烯和9-羟基 - 苯并[A] pyrene将得到特殊验证 为此，通过实现以下特定目标。目标1是 在尿液浓度和BAP之间建立定量关系 暴露于24小时的平均个人空气浓度和 24小时饮食摄入量。目标2是检查是否有重要 研究对象中尿标记浓度的日常变化 稳定的每日PAH暴露。这很重要，因为生物标志物成为 对于估计癌症风险有用，该标记应该能够预测 人们的平均水平（稳定）暴露。 AIM 3是检查是否第一个 早晨的尿液样本可以有效地表示每日暴露或24小时 需要复合尿液样本。这很重要，因为 24小时的尿液样品很难获得自由生活的人群。 目标4是检查尿标记与其他PAH之间的关系 指标，因为PAH混合物的其他指标可能被证明是更好的索引 用于未来的风险评估。该研究将在100个非吸烟中进行 接触空中bap的成年人，包括 职业和非占领的个人。这是必要的 为了评估这些生物标志物在更广泛应用中的有效性， 因为高PAH暴露不仅可以在许多职业环境中发生 而且还包括其他人的日常生活，包括非吸烟者。研究 每个受试者将由两组重复测量组成。每组 测量的包括：24小时个人呼吸区浓度 气相和粒子相PAH； 24小时饮食PAH摄入量；生物标志物 第一个早晨尿液和24小时复合尿液中的浓度。所有这些 测量将在同一24小时内进行。两个重复 每个受试者的测量将至少三个月 最大化日常暴露的代表性。空气样品和食物 将对至少16个普通PAH（包括pyrene和bap）分析样品 使用已建立的HPLC/荧光方法。尿的斑点本质 浓度将用肌酐纠正。统计方法是 使用的将包括描述性分析，散点图，相关分析， 配对比较和线性混合模型。在混合模型，年龄，性别中 高度，体重和体重指数将被调整。