Abstract
Background: The etiology of childhood cancer is poorly understood. The role of environmental factors, including air pollution (AP) exposure, has been addressed previously, but results so far have been inconclusive. In this study, we investigate the association between long-term AP exposures in relation to childhood cancer subtypes in Denmark (1981À2013). Methods: We conducted a nationwide register-based case-control study. We identified 7745 incident cases of childhood cancers (<20 years) in the Danish Cancer Registry. Four randomly selected (cancer-free) controls were matched to each case according to sex and date of birth. We modelled concentrations of nitrogen dioxide (NO 2), fine particles (PM 2¢5), and black carbon (BC) at all addresses and calculated a time-weighted average from birth to index-date with a state-of-the-art multiscale AP modelling system. We analyzed the risk of childhood cancer in conditional logistic regression models adjusted for socio-demographic variables obtained from registers at the individual and neighborhood level. Findings: The main analyses included 5045 cases and 18,179 controls. For all cancers combined, we observed odds ratios (ORs) and 95% confidence intervals (95% CI) of 0¢97 (0¢94, 1¢01) per 10 mg/m 3 NO 2 , 0¢89 (0¢82, 0¢98) per 5 mg/m 3 PM 2¢5 , and 0¢94 (0¢88, 1¢01) per 1 mg/m 3 BC, respectively. Most notably, we observed a higher risk of Non-Hodgkin Lymphoma (NHL) with higher childhood AP exposure with ORs and 95% CIs of 1¢21 (0¢94, 1¢55) per 10 mg/m 3 NO 2 , 2¢11 (1¢10, 4¢01) per 5 mg/m 3 PM 2¢5 , and 1¢68 (1¢06, 2¢66) per 1 mg/m 3 BC, respectively. We observed indications of increased risks for other types of childhood cancer, however, with very wide CIs including 1. Interpretations: The findings of this nationwide study propose a role of AP in the development of childhood NHL, but more large-scale studies are needed. Funding: NordForsk Project #75007.