Summary effect size
The summary fixed effects estimates were significant in 257 of 509 meta-analyses (50%), while the summary random effects estimates were significant in 207 associations (41%) at a threshold ofp <0.05 (Supplementary Table 4). At a stricter threshold (p <0.001), 114 (22%) and 77 (15%) meta-analyses were statistically significant using fixed and random effects models, respectively. When the p -value was set at 10-6, 43 (8%) fixed effects estimates and 21 (4%) random effects estimates were statistically significant.
Of the 21 statistically significant summary random effect sizes atp <10-6 (Supplementary Table 4), 13 showed a significant association between high birthweight, paternal smoking, maternal alcohol consumption, exposure to benzene, rural population mixing, as well as residential and occupational exposure to pesticides, especially insecticides and childhood leukemia risk. The magnitude of these effect sizes ranged between 1.19 for high birthweight and 3.30 for maternal occupational pesticide exposure. In addition, four summary random effects estimates found a decreased risk for childhood leukemia at p <10-6 in relation to maternal dietary vitamin intake during pregnancy (summary OR: 0.81, 95%CI: 0.74, 0.88), maternal multivitamin supplementation during pregnancy (summary OR: 0.64, 95%CI: 0.52, 0.80), breastfeeding for more than 6 months (summary OR: 0.76, 95%CI: 0.68, 0.84), and high maternal education (summary OR: 0.81, 95%CI: 0.76, 0.87). The remaining 4 out of 21 significant effect sizes found an increased risk for CNS tumors, and especially astrocytomas in relation to high birthweight, as well as for testicular cancer in relation to testicular microlithiasis and isolated cryptorchidism.
The largest study in each meta-analysis was statistically significant in 186 of 509 associations (37%), albeit the effect sizes of the largest studies were in general more conservative than the respective summary random effects estimates (Supplementary Table 4).