Systematic Reviews and Meta- and Pooled Analyses Parental, In Utero, and Early-Life Exposure to Benzene and the Risk of Childhood Leukemia: A Meta-Analysis

Benzene is an established cause of adult leukemia, but whether it is associated with childhood leukemia remains unclear. We conducted ameta-analysis in which we reviewed the epidemiologic literature on this topic and explored causal inference, bias, and heterogeneity. The exposure metrics that we evaluated included occupational and household use of benzenes and solvents, traffic density, and traffic-related air pollution. For studies of occupational and household product exposure published from 1987 to 2014, the summary relative risk for childhood leukemia was 1.96 (95% confidence interval (CI): 1.53, 2.52; n = 20). In these studies, the summary relative risk was higher for acute myeloid leukemia (summary relative risk (sRR) = 2.34, 95% CI: 1.72, 3.18; n = 6) than for acute lymphoblastic leukemia (sRR = 1.57; 95%CI: 1.21, 2.05; n = 14). The summary relative risk was higher for maternal versus paternal exposure, in studies that assessed benzene versus all solvents, and in studies of gestational exposure. In studies of traffic density or traffic-related air pollution published from 1999 to 2014, the summary relative risk was 1.48 (95%CI: 1.10, 1.99; n = 12); it was higher for acute myeloid leukemia (sRR = 2.07; 95%CI: 1.34, 3.20) than for acute lymphoblastic leukemia (sRR = 1.49; 95%CI: 1.07, 2.08) and in studies that involved detailedmodels of traffic pollution (sRR = 1.70; 95% CI: 1.16, 2.49). Overall, we identified evidence of associations between childhood leukemia and several different potential metrics of benzene exposure.