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Validation and calibration of a model used to reconstruct historical exposure to polycyclic aromatic hydrocarbons for use in epidemiologic studies.

ABSTRACT: OBJECTIVES:We previously developed a historical reconstruction model to estimate exposure to airborne polycyclic aromatic hydrocarbons (PAHs) from traffic back to 1960 for use in case-control studies of breast cancer risk. Here we report the results of four exercises to validate and calibrate the model. METHODS:Model predictions of benzo[a]pyrene (BaP) concentration in soil and carpet dust were tested against measurements collected at subjects' homes at interview. In addition, predictions of air intake of BaP were compared with blood PAH-DNA adducts. These same soil, carpet, and blood measurements were used for model optimization. In a separate test of the meteorological dispersion part of the model, predictions of hourly concentrations of carbon monoxide from traffic were compared with data collected at a U.S. Environmental Protection Agency monitoring station. RESULTS:The data for soil, PAH-DNA adducts, and carbon monoxide concentrations were all consistent with model predictions. The carpet dust data were inconsistent, suggesting possible spatial confounding with PAH-containing contamination tracked in from outdoors or unmodeled cooking sources. BaP was found proportional to other PAHs in our soil and dust data, making it reasonable to use BaP historical data as a surrogate for other PAHs. Road intersections contributed 40-80% of both total emissions and average exposures, suggesting that the repertoire of simple markers of exposure, such as traffic counts and/or distance to nearest road, needs to be expanded to include distance to nearest intersection.

SUBMITTER: Beyea J

PROVIDER: S-EPMC1513337 | biostudies-literature | 2006 Jul

REPOSITORIES: biostudies-literature

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Validation and calibration of a model used to reconstruct historical exposure to polycyclic aromatic hydrocarbons for use in epidemiologic studies.

Beyea Jan J Hatch Maureen M Stellman Steven D SD Santella Regina M RM Teitelbaum Susan L SL Prokopczyk Bogdan B Camann David D Gammon Marilie D MD

Environmental health perspectives 20060701 7

<h4>Objectives</h4>We previously developed a historical reconstruction model to estimate exposure to airborne polycyclic aromatic hydrocarbons (PAHs) from traffic back to 1960 for use in case-control studies of breast cancer risk. Here we report the results of four exercises to validate and calibrate the model.<h4>Methods</h4>Model predictions of benzo[a]pyrene (BaP) concentration in soil and carpet dust were tested against measurements collected at subjects' homes at interview. In addition, pre ...[more]

PMID: 16835058

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Project description:BackgroundAging is related to an increased risk of morbidity and mortality and is affected by environmental factors. Exposure to polycyclic aromatic hydrocarbons (PAHs) is associated with adverse health outcomes; but the association of such exposure with DNA methylation aging, a novel aging marker, is unclear.ObjectivesOur aim was to investigate the association of PAH exposure with methylation aging.MethodsWe trained and validated a methylation age predictor suitable for Chinese populations using whole blood methylation data in 989 Chinese and 160 Caucasians. We defined two aging indicators: δage, as methylation age minus chronological age; and aging rate, the ratio of methylation to chronological age. The association of PAH exposure with aging indicators was evaluated using linear regressions in three panels of healthy Chinese participants (N=539, among the aforementioned 989 Chinese participants) whose exposure levels were assessed by 10 urinary monohydroxy-PAH metabolites.ResultsWe developed a methylation age predictor providing accurate predictions in both Chinese individuals and Caucasian persons (R=0.94-0.96, RMSE=3.8-4.3). Among the 10 urinary metabolites that we measured, 1-hydroxypyrene and 9-hydroxyphenanthrene were associated with methylation aging independently of other OH-PAHs and risk factors; 1-unit increase in 1-hydroxypyrene was associated with a 0.53-y increase in Δage [95% confidence interval (CI): 0.18, 0.88; false discovery rate (FDR) FDR=0.004] and 1.17% increase in aging rate (95% CI: 0.36, 1.98; FDR=0.02), whereas for 9-hydroxyphenanthrene, the increase was 0.54-y for Δage (95% CI: 0.17, 0.91; FDR=0.004), and 1.15% for aging rate (95% CI: 0.31, 1.99; FDR=0.02). The association direction was consistent across the three Chinese panels with the association magnitude correlating with the panels' exposure levels; the association was validated by methylation data of purified leukocytes. Several cytosine-phosphoguanines, including those located on FHL2 and ELOVL2, were found associated with both aging indicators and monohydroxy-PAH levels.ConclusionsWe developed a methylation age predictor specific for Chinese populations but also accurate for Caucasian populations. Our findings suggest that exposure to PAHs may be associated with an adverse impact on human aging and epigenetic alterations in Chinese populations. https://doi.org/10.1289/EHP2773.

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Validation and calibration of a model used to reconstruct historical exposure to polycyclic aromatic hydrocarbons for use in epidemiologic studies.

Publications

Validation and calibration of a model used to reconstruct historical exposure to polycyclic aromatic hydrocarbons for use in epidemiologic studies.

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