Meta-analysis Of The Correlation Between NUDT15 Gene Polymorphism And 6-MP Toxicity During Chemotherapy In Childhood Acute Lymphoblastic Leukemia

Objective To systematically evaluate the correlation between the c.415C>T polymorphism of NUDT15 gene and the toxicity of6-mercaptopurine(6-MP)in chemotherapy in children with acute lymphoblastic leukemia(ALL),and to provide evidence-based medicine for clinical individualized treatment.Methods Systematic search of relevant domestic and foreign databases: Pub Med,Em Base,Cochrane Library,CNKI,CBM,VIP Chinese Sci-tech Journal Database,and Wanfang Database.The language is limited to Chinese or English.A case-control study or cohort study of6-MP treatment of childhood acute lymphoblastic leukemia related to the toxicity of the NUDT15 gene c.415C>T locus polymorphism was included.The search time limit is from the establishment of the database to October 1,2020.Two researchers independently screened the literature,extracted data from the literature that met the inclusion criteria,and evaluated the quality of the included studies.Rev Man 5.3 and Stata 12.0software were used to analyze the NUDT15 gene c.415C>T under different genetic models.The correlation between locus polymorphism and toxicity during 6-MP chemotherapy was analyzed by Meta analysis.Results 9 studies were finally included,8 were cohort studies,and 1was a case-control study,with a total of 1 068 children.Meta-analysis results showed that the c.415C>T site mutation of NUDT15 gene was associated with leukopenia [TT+CT vs.CC : OR = 4.53,95 % CI(2.74,7.49),P<0.001;TT vs.CT+CC:OR=11.06,95%CI(3.04,40.29),P<0.001;CT vs.CC:OR=3.73,95%CI(2.19,6.36),P<0.001;TT vs.CC:OR=15.68,95%CI(4.21,58.48),P<0.001;T vs.C:OR=4.95,95%CI(3.13,7.82),P<0.001] and neutropenia[TT+CT vs.CC:OR=5.54,95%CI(2.08,14.76),P =0.001;TT vs.CT+CC:OR=7.33,95%CI(1.93,27.83),P =0.003;CT vs.CC:OR=4.81,95%CI(1.54,15.02),P =0.007;TT vs.CC:OR=9.49,95%CI(2.38,37.86),P =0.001;T vs.C:OR=5.09,95%CI(2.40,10.79),P<0.001],there is a significant correlation,but there is no significant correlation with the risk of hepatotoxicity under the five genetic models(all P>0.05).Conclusions The mutation at c.415C>T of NUDT15 gene significantly increases the incidence of leukopenia and neutropenia during 6-MP chemotherapy,but has no significant effect on the occurrence of hepatotoxicity.