机构：[1]Department of Pharmacy, Beijing Children’s Hospital, Capital Medical University, Beijing, China[2]Department of Pharmacy, Xuanwu Hospital of Capital Medical University, Beijing, China首都医科大学宣武医院[3]Department of Pharmacy Administration and Clinical Pharmacy, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing, China.
As a common chemotherapy drug, methotrexate (MTX) has achieved remarkable clinical success. However, high inter-individual variability and unpredictable toxicity continue to challenge its use in clinical practices. Some studies suggest this variation is associated with a methylenetetrahydrofolate reductase (MTHFR) gene polymorphism, but results remain unclear. In this meta-analysis, we include 14 studies that focus on MTHFR C677T and A1298C polymorphisms in pediatric patients with malignancy. We found significant associations of the MTHFR C677T polymorphism with hepatotoxicity (grade >= 2; CC vs CT/TT: risk ratio (RR): 0.82, 95% confidence interval (CI): 0.67-0.99; P = 0.04), hematological toxicity (grade 3-4; CC vs CT/TT: RR: 0.65, 95% CI: 0.44-0.97; P=0.03) in a dominant genetic model and mucositis (grade >= 3) in all models (CC vs CT/TT: RR: 0.18, 95% CI: 0.04-0.87; P-0.03; CC/CT vs TT: RR: 0.10, 95% CI: 0.03-0.32; P <= 0.0001; CC vs TT: RR: 0.10, 95% CI: 0.02-0.50; P= 0.005). No significant association was found with the MTHFR A1298C polymorphism. For children with malignancy, genotyping of the MTHFR C677T polymorphism is expected to be a useful tool in reducing toxicity and improving outcome in personalized MTX therapy.
第一作者机构：[1]Department of Pharmacy, Beijing Children’s Hospital, Capital Medical University, Beijing, China[2]Department of Pharmacy, Xuanwu Hospital of Capital Medical University, Beijing, China
共同第一作者：
通讯作者：
通讯机构：[*1]Department of Pharmacy, Beijing Children’s Hospital, Capital Medical University, 56 Nanlishi Road, Xicheng District, Beijing 100045, China.
推荐引用方式(GB/T 7714)：
C Zhu,YW Liu,SZ Wang,et al.Associations between the C677T and A1298C polymorphisms of MTHFR and the toxicity of methotrexate in childhood malignancies: a meta-analysis[J].PHARMACOGENOMICS JOURNAL.2018,18(3):450-459.doi:10.1038/tpj.2017.34.
APA：
C Zhu,YW Liu,SZ Wang,XL Li,XL Nie...&XL Wang.(2018).Associations between the C677T and A1298C polymorphisms of MTHFR and the toxicity of methotrexate in childhood malignancies: a meta-analysis.PHARMACOGENOMICS JOURNAL,18,(3)
MLA：
C Zhu,et al."Associations between the C677T and A1298C polymorphisms of MTHFR and the toxicity of methotrexate in childhood malignancies: a meta-analysis".PHARMACOGENOMICS JOURNAL 18..3(2018):450-459
