Validation of PAH Biomarkers for Quantifying Cancer Risk

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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.