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

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