Effects of Genetic Polymorphisms of WNT Signaling Pathway on the Prognosis of Acute Lymphoblastic Leukemia in Chinese Pediatric Population

The deregulation of WNT signaling has been shown to be important in the development of hematologic malignancies. The genetic variation of key WNT signaling pathway genes may affect the development of leukemia. In the present study, a total of 20 single nucleotide polymorphisms (SNPs) in 6 genes ( CTNNB1, AXIN2, SFRP2, SFRP4, SFRP5 , and DKK3 ) involved in the WNT signaling pathway were selected to investigate the influence of SNPs on the prognosis of 379 Chinese children with acute lymphoblastic leukemia (ALL). Both χ 2 test and Kaplan-Meier survival curve estimation showed that AXIN2 rs7591, rs3923086, and rs11867417 were associated with the risk of relapse with statistical significance. The multifactorial analyses showed that the 3 SNPs of rs7591, rs3923086, and rs11867417 in AXIN2 still had a significant effect on prognosis with statistical significance ( P =0.004, 0.019, and 0.013, respectively). In addition, SFRP4 rs1802073 and rs1802074 were also significantly associated with the risk of relapse after excluding the effect of confounding variables. Taken together, our findings show that polymorphisms in AXIN2 and SFRP4 were independent prognostic predictors for pediatric ALL patients. Further studies are needed to validate these findings and clarify the underlying mechanism.