Association Of MTHFR And SLC19A1 Gene Polymorphisms With Methotrexate Toxicity In Chemotherapy Of Acute Lymphoblastic Leukemia: A Meta Analysis

Purpose: To systematically evaluate the correlation between MTHFR,SLC19A1 gene polymorphisms and methotrexate toxicity in acute lymphoblastic leukemia chemotherapy,so as to determine whether the gene can be used as a predictive indicator of methotrexate toxicity,and to provide evidence-based basis for clinical individual treatment of methotrexate.Methods: All the studies on the relationship between MTHFR,SLC19A1 gene polymorphisms and methotrexate in chemotherapy of all were searched by using database,including EMBASE,Pub Med and Cochrane Library;Chinese databases: Wanfang database,CBM,CNKI and VIP.The inclusion and exclusion criteria were strictly established.According to the screening process,the clinical studies meeting the criteria were metaanalyzed.The outcome index was the toxicity of chemotherapy.The association between single nucleotide polymorphism and or was evaluated by calculating the combined effect or and 95% CI.The data were analyzed by Review Manager 5.4 software.Results: 21 cohort studies were included,of which 15 focused on MTHFR C677T,13 on MTHFR A1298 C and 6 on SLC19A1 G80 A.Meta analysis showed that The MTHFR C677T mutation increased the risk of gastrointestinal toxicity in ALL patients(CT+TT vs.CC:OR=1.53,95%CI:1.09-2.14,P=0.01;T vs.C:OR=1.68,95%CI:1.02-2.75,P=0.04)and the risk of hepatotoxicity in people aged 18 years OR older(T vs.C:OR=2.13,95%CI:1.24-3.66,P=0.006).The risk of hepatotoxicity was significantly lower in the 18-year-old population(T vs.C:OR=0.71,95%CI:0.53-0.94,P=0.02),and significantly lower in the yellow population carrying SLC19A1 G80 A wild allele(GA+GG vs.AA:OR=0.33,95%CI:0.17-0.63,P=0.0008).Conclusion: MTHFR C677T mutation increases the risk of hepatotoxicity and gastrointestinal toxicity during MTX chemotherapy in all patients.MTHFR A1298 C Polymorphism is not associated with oral mucositis,hepatotoxicity and gastrointestinal toxicity.SLC19A1 G80 A wild G allele is a protective factor for the risk of hepatotoxicity in Asian.