Does outdoor air pollution cause childhood leukemia? A systematic review and dose-response meta-analysis

A causal link between outdoor air pollution from motorized traffic and childhood leukemia has been proposed, but some older studies suffer from methodological drawbacks and no analyses have examined the dose-response relation. In this review, we investigated the extent to which outdoor air pollution, especially as resulting from traffic-related contaminants, affects the risk of childhood leukemia. We performed online database search up to October 10, 2019, including also snowballing methods to retrieve all possible case-control and cohort eligible studies. We carried out a meta-analysis, whenever possible with a dose-response approach using a restricted cubic spline regression model, our intent being to investigate the extent to which air pollution, especially in regard to traffic-related contaminants, affects the risk of childhood leukemia. We found 30 studies eligible to be included in our review. Exposure assessment either to motorized traffic and related contaminants was based on various traffic-related metrics (number of vehicles in the closest roads, road density, and distance from major roads), or on measured or modeled levels of air contaminants such as benzene, nitrogen dioxide, 1,3-butadiene, and particulate matter. In the dose-response analysis, we found an indication of increased but imprecise association between disease risk and traffic indicators, measured as number of vehicles in the closest roads, road density, and distance from major roads near the child’s residence, only at the highest levels of exposure. Similarly, exposure to nitrogen dioxide showed little association with leukemia risk except at the highest levels. Conversely, we found that benzene exposure was positively and approximately linearly associated with risk of childhood leukemia, particularly for acute myeloid leukemia, among children under 6 years of age, and when exposure assessment at the time of diagnosis was used. Overall, the summarized epidemiologic literature appears to support an association between benzene emissions from traffic exhausts and childhood leukemia risk, especially the myeloid subtype and in the youngest children, with no indication of any threshold.