Relationship between methylenetetrahydrofolate reductase gene polymorphism and methotrexate toxicities in childhood acute lymphoblastic leukemia chemotherapy
10.3969/j.issn.1000-3606.2018.06.016
- VernacularTitle:亚甲基四氢叶酸还原酶基因多态性与儿童急性淋巴细胞白血病化疗中甲氨蝶呤毒性相关性的meta分析
- Author:
Xianrui CHEN
1
;
Jianqi HUANG
;
Jinzhun WU
;
Haitao BAI
Author Information
1. 厦门大学附属第一医院儿科 福建厦门 361000
- Keywords:
acute lymphoblastic leukemia;
methylenetetrahydrofolate reductase;
methylaminopterin;
genetic polymorphism;
meta-analysis
- From:
Journal of Clinical Pediatrics
2018;36(6):467-475
- CountryChina
- Language:Chinese
-
Abstract:
Objective To evaluate the association between methylenetetrahydrofolate reductase (MTHFR) gene C677T polymorphism and susceptibility to methotrexate (MTX) adverse reaction in children with acute lymphoblastic leukemia (ALL) chemotherapy. Method The data bases of The Cochrane Library, PubMed, EMbase, EMCC, OVID, CNKI, VIP and WanFang Data were searched for relevant articles published in English and Chinese up to March 2016. Two researchers independently screened literature, extracted data, and assessed bias risk in the included studies. The RevMan 5.3 and Stata 12 software were used to analyze the association between gene polymorphism and the adverse reaction of MTX chemotherapy with the recessive, dominance, co-dominance, addition and allele gene model respectively. Results A total of 12 studies were included and all of them were case-control study, with 1419 cases in case group and 2188 cases in control group. The results of meta-analysis showed that the MTHFR gene polymorphism was unrelated to the untoward effect of neutropenia, thrombocytopenia, hemoglobin reduction, mucosal damage and liver function damage during MTX chemotherapy in children with ALL under the 5 analytical models. Under the co-dominance gene model, the association between MTHFR polymorphism C677T and overall adverse reaction of MTX was statistically significant (OR=1.39, 95％CI: 1.02～1.91, P=0.04). In the recessive gene model, the C677T polymorphism of MTHFR was associated with a reduced risk of gastrointestinal adverse reactions during MTX chemotherapy (OR=3.31, 95％CI: 1.03～10.59, P=0.04). In the dominance gene model, the C677T polymorphism of MTHFR was associated with a reduced risk of skin damage induced by MTX chemotherapy (OR=3.05, 95％CI: 1.25～7.41, P=0.01). Conclusion There is no significant association between the C677T polymorphism of MTHFR and the adverse effects of MTX chemotherapy, butfurther studies with larger sample size are needed.
