SynthesisThe pharmacogenomics journal2018
Associations between the C677T and A1298C polymorphisms of MTHFR and the toxicity of methotrexate in childhood malignancies: a meta-analysis.
Synthesis in The pharmacogenomics journal, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 3 of them syntheses that pooled it.
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Who cites it
14 citing papers in PubMed, 3 syntheses or guidelines pooled it, 29 citations in OpenAlex.
- Correlation between gene polymorphism and adverse reactions of high-dose methotrexate in osteosarcoma patients: a systematic review and meta-analysis.World journal of surgical oncology · 2024Pooled it
- Association betweenFrontiers in endocrinology · 2023Pooled it
- Genetic markers in methotrexate treatments.The pharmacogenomics journal · 2018Pooled it
- Impact of Pharmacogenetics on High-Dose Methotrexate Toxicity in Pediatric Oncology.Pharmaceutics · 2025Article
- An interactive dose optimizer based on population pharmacokinetic study to guide dosing of methotrexate in Chinese patients with osteosarcoma.Cancer chemotherapy and pharmacology · 2024Article
- Involvement of theInternational journal of general medicine · 2024Article
- Relationship between methylenetetrahydrofolate reductase gene polymorphisms and methotrexate drug metabolism and toxicity.Translational pediatrics · 2023Article
- The Role of Genetic Polymorphisms in High-Dose Methotrexate Toxicity and Response in Hematological Malignancies: A Systematic Review and Meta-Analysis.Frontiers in pharmacology · 2021Article
- The influence of MTHFR genetic polymorphisms on methotrexate therapy in pediatric acute lymphoblastic leukemia.Open life sciences · 2021Article
- Polymorphisms within methotrexate pathway genes: Relationship between plasma methotrexate levels, toxicity experienced and outcome in pediatric acute lymphoblastic leukemia.Iranian journal of basic medical sciences · 2020Article
- Article
- Pharmacogenomics as a Tool to Limit Acute and Long-Term Adverse Effects of Chemotherapeutics: An Update in Pediatric Oncology.Frontiers in pharmacology · 2020Review
- Implementation of Pharmacogenetics to Individualize Treatment Regimens for Children with Acute Lymphoblastic Leukemia.Pharmacogenomics and personalized medicine · 2020Review
- Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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.
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