Polymorphisms in innate immunity genes and risk of childhood leukemia.

The immune system plays an important role in the control of cancer development. To investigate possible genetic contribution to childhood leukemia risk in the innate immune system, we performed an association study for the 1214 SNPs in 146 gene regions related to innate immunity using GoldenGate (Illumina) oligonucleotide pool assay (OPA) in 106 case patients and 123 controls. Childhood leukemia risk was estimated as odds ratios and 95% confidence intervals adjusted for age, gender and birth weight. The minP test was used to identify statistically significant association at gene level. Three SNPs (STAT6 rs703817, C1qG rs17433222, and MBP rs3794845) were significantly associated with childhood leukemia risk (p(trend) < 0.001, minP < 0.01). The most significant association with childhood leukemia risk was for STAT6 rs703817 (GA vs GG: 0.48 (0.26-0.87), AA vs GG: 0.21 (0.07-0.61), p(trend) = 0.0003, minP = 0.002). Subgroup analysis showed that Ly96 rs78380171 and MBP rs3794845 were significantly associated with the risk of acute lymphoblastic leukemia (p(trend) < 0.001). Our results suggest that genetic polymorphisms in innate immunity genes might play a role in the genesis of childhood leukemia with limited biologic evidence. Additional, larger studies are needed to identify the mechanism of these genes in childhood leukemia patients.