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      Association between Outdoor Air Pollution and Childhood Leukemia: A Systematic Review and Dose–Response Meta-Analysis

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          Abstract

          Background:

          A causal link between outdoor air pollution and childhood leukemia has been proposed, but some older studies suffer from methodological drawbacks. To the best of our knowledge, no systematic reviews have summarized the most recently published evidence and no analyses have examined the dose–response relation.

          Objective:

          We investigated the extent to which outdoor air pollution, especially as resulting from traffic-related contaminants, affects the risk of childhood leukemia.

          Methods:

          We searched all case–control and cohort studies that have investigated the risk of childhood leukemia in relation to exposure either to motorized traffic and related contaminants, based on various traffic-related metrics (number of vehicles in the closest roads, road density, and distance from major roads), or to measured or modeled levels of air contaminants such as benzene, nitrogen dioxide, 1,3-butadiene, and particulate matter. We carried out a meta-analysis of all eligible studies, including nine studies published since the last systematic review and, when possible, we fit a dose–response curve using a restricted cubic spline regression model.

          Results:

          We found 29 studies eligible to be included in our review. In the dose–response analysis, we found little association between disease risk and traffic indicators near the child’s residence for most of the exposure range, with an indication of a possible excess risk only at the highest levels. In contrast, benzene exposure was positively and approximately linearly associated with risk of childhood leukemia, particularly for acute myeloid leukemia, among children under 6 y of age, and when exposure assessment at the time of diagnosis was used. Exposure to nitrogen dioxide showed little association with leukemia risk except at the highest levels.

          Discussion:

          Overall, the epidemiologic literature appears to support an association between benzene and childhood leukemia risk, with no indication of any threshold effect. A role for other measured and unmeasured pollutants from motorized traffic is also possible. https://doi.org/10.1289/EHP4381

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          One-stage dose–response meta-analysis for aggregated data

          Alessio Crippa, Andrea Discacciati, Matteo Bottai … (2018)
          The standard two-stage approach for estimating non-linear dose-response curves based on aggregated data typically excludes those studies with less than three exposure groups. We develop the one-stage method as a linear mixed model and present the main aspects of the methodology, including model specification, estimation, testing, prediction, goodness-of-fit, model comparison, and quantification of between-studies heterogeneity. Using both fictitious and real data from a published meta-analysis, we illustrated the main features of the proposed methodology and compared it to a traditional two-stage analysis. In a one-stage approach, the pooled curve and estimates of the between-studies heterogeneity are based on the whole set of studies without any exclusion. Thus, even complex curves (splines, spike at zero exposure) defined by several parameters can be estimated. We showed how the one-stage method may facilitate several applications, in particular quantification of heterogeneity over the exposure range, prediction of marginal and conditional curves, and comparison of alternative models. The one-stage method for meta-analysis of non-linear curves is implemented in the dosresmeta R package. It is particularly suited for dose-response meta-analyses of aggregated where the complexity of the research question is better addressed by including all the studies.
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            Distance-weighted traffic density in proximity to a home is a risk factor for leukemia and other childhood cancers.

            Kristie L. Ebi, Talima Pearson, H Wachtel (2000)
            Occupational exposure to elevated concentrations of benzene is a known cause of leukemia in adults. Concentrations of benzene from motor vehicle exhaust could be elevated along highly trafficked streets. Several studies have reported significant associations between proximity to highly trafficked streets and the occurrence of childhood cancers and childhood leukemia. These associations may be due to chronic exposure to benzene or other carcinogenic components of vehicle exhaust from these nearby streets or to some other factor (e.g., noise, increased light exposure, or some unaccounted--for socioeconomic variable). We used data for homes studied in an earlier childhood cancer study conducted in Denver, CO, in the 1980s. No air pollution measurements were made in the original study. We identified the highest trafficked street near each study home and obtained the traffic density in 1979 and 1990. Traffic density was weighted for the distance from the street to the home using 3 different widths of Gaussian curves to approximate the decay of the emissions into the surrounding neighborhoods. The associations between the 750-ft-wide distance-weighted traffic density metrics and all childhood cancers and childhood leukemia are strongest in the highest traffic density category (> or = 20,000 vehicles per day [VPD]). The odds ratio is 5.90 (95% confidence interval [CI] 1.69-20.56) for all cancers and 8.28 (95% CI 2.09-32.80) for leukemia. The results are suggestive of an association between proximal high traffic streets with traffic counts > or = 20,000 VPD and childhood cancer, including leukemia.
            Article 0 comments Cited 61 times – based on 0 reviews     Review now
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              Comparing exposure assessment methods for traffic-related air pollution in an adverse pregnancy outcome study.

              Beate Ritz, Judith Chung, Michelle Wilhelm … (2011)
              Previous studies reported adverse impacts of traffic-related air pollution exposure on pregnancy outcomes. Yet, little information exists on how effect estimates are impacted by the different exposure assessment methods employed in these studies. To compare effect estimates for traffic-related air pollution exposure and preeclampsia, preterm birth (gestational age less than 37 weeks), and very preterm birth (gestational age less than 30 weeks) based on four commonly used exposure assessment methods. We identified 81,186 singleton births during 1997-2006 at four hospitals in Los Angeles and Orange Counties, California. Exposures were assigned to individual subjects based on residential address at delivery using the nearest ambient monitoring station data [carbon monoxide (CO), nitrogen dioxide (NO(2)), nitric oxide (NO), nitrogen oxides (NO(x)), ozone (O(3)), and particulate matter less than 2.5 (PM(2.5)) or less than 10 (PM(10))μm in aerodynamic diameter], both unadjusted and temporally adjusted land-use regression (LUR) model estimates (NO, NO(2), and NO(x)), CALINE4 line-source air dispersion model estimates (NO(x) and PM(2.5)), and a simple traffic-density measure. We employed unconditional logistic regression to analyze preeclampsia in our birth cohort, while for gestational age-matched risk sets with preterm and very preterm birth we employed conditional logistic regression. We observed elevated risks for preeclampsia, preterm birth, and very preterm birth from maternal exposures to traffic air pollutants measured at ambient stations (CO, NO, NO(2), and NO(x)) and modeled through CALINE4 (NO(x) and PM(2.5)) and LUR (NO(2) and NO(x)). Increased risk of preterm birth and very preterm birth were also positively associated with PM(10) and PM(2.5) air pollution measured at ambient stations. For LUR-modeled NO(2) and NO(x) exposures, elevated risks for all the outcomes were observed in Los Angeles only--the region for which the LUR models were initially developed. Unadjusted LUR models often produced odds ratios somewhat larger in size than temporally adjusted models. The size of effect estimates was smaller for exposures based on simpler traffic density measures than the other exposure assessment methods. We generally confirmed that traffic-related air pollution was associated with adverse reproductive outcomes regardless of the exposure assessment method employed, yet the size of the estimated effect depended on how both temporal and spatial variations were incorporated into exposure assessment. The LUR model was not transferable even between two contiguous areas within the same large metropolitan area in Southern California. Copyright © 2011 Elsevier Inc. All rights reserved.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Environ Health Perspect
                Journal ID (iso-abbrev): Environ. Health Perspect
                Journal ID (publisher-id): EHP
                Title: Environmental Health Perspectives
                Publisher: Environmental Health Perspectives
                ISSN (Print): 0091-6765
                ISSN (Electronic): 1552-9924
                Publication date (Electronic): 24 April 2019
                Publication date Collection: April 2019
                Volume: 127
                Issue: 4
                Electronic Location Identifier: 046002
                Affiliations
                [ 1 ]Environmental, Genetic and Nutritional Epidemiology Research Center (CREAGEN), Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia , Modena, Italy
                [ 2 ]Department of Epidemiology, Boston University School of Public Health , Boston, Massachusetts, USA
                [ 3 ]RTI Health Solutions , Research Triangle Park, North Carolina, USA
                [ 4 ]Department of Epidemiology, UCLA Fielding School of Public Health , Los Angeles, California, USA
                [ 5 ]Department of Medical Epidemiology and Biostatistics, Karolinska Institutet , Stockholm, Sweden
                [ 6 ]Department of Public Health Sciences, Karolinska Institutet , Stockholm, Sweden
                Author notes
                Address correspondence to Marco Vinceti, CREAGEN, Department of Biomedical, Metabolic and Neural Sciences, UNIMORE, Via Campi 287, Modena 41125 Italy. Email: marco.vinceti@ 123456unimore.it
                Article
                Publisher ID: EHP4381
                DOI: 10.1289/EHP4381
                PMC ID: 6785230
                PubMed ID: 31017485
                SO-VID: 57a3e2f2-3d8c-43ec-afee-061f63bc975c
                License:

                EHP is an open-access journal published with support from the National Institute of Environmental Health Sciences, National Institutes of Health. All content is public domain unless otherwise noted.

                History
                Date received : 23 August 2018
                Date revision received : 22 March 2019
                Date accepted : 26 March 2019
                Categories
                Subject: Review

                ScienceOpen disciplines: Public health
                Data availability:
                ScienceOpen disciplines: Public health

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