SynthesisTumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine2012
Impact of methylenetetrahydrofolate reductase (MTHFR) polymorphisms on methotrexate-induced toxicities in acute lymphoblastic leukemia: a meta-analysis.
Synthesis in Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 7 of them syntheses that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
40 citing papers in PubMed, 7 syntheses or guidelines pooled it, 82 citations in OpenAlex.
- The impact of gene polymorphisms on the response of methotrexate-based treatments.European journal of clinical pharmacology · 2026Pooled it
- Genetic markers in methotrexate treatments.The pharmacogenomics journal · 2018Pooled it
- Associations between the C677T and A1298C polymorphisms of MTHFR and the toxicity of methotrexate in childhood malignancies: a meta-analysis.The pharmacogenomics journal · 2018Pooled it
- Pooled it
- Neurocognitive outcomes in long-term survivors of childhood acute lymphoblastic leukemia treated on contemporary treatment protocols: A systematic review.Neuroscience and biobehavioral reviews · 2015Pooled it
- Association of the MTHFR C677T and A1298C polymorphisms with methotrexate toxicity in rheumatoid arthritis: a meta-analysis.Clinical rheumatology · 2014Pooled it
- Association between methylenetetrahydrofolate reductase polymorphisms and the relapse of acute lymphoblastic leukemia: a meta-analysis.The pharmacogenomics journal · 2014Pooled it
- Influence of Folate-Related Gene Polymorphisms on High-Dose Methotrexate-Related Toxicity and Prognosis in Turkish Children with Acute Lymphoblastic Leukemia.Turkish journal of haematology : official journal of Turkish Society of Haematology · 2017Trial
- Association of Variants in Candidate Pharmacogenes with Response to Mercaptopurine and Methotrexate in Pediatric Acute Lymphoblastic Leukemia: A Single-Center Experience from Croatia.Oncology and therapy · 2026Article
- [Association ofZhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics · 2026Article
- Pharmacogenomics of treatment toxicities in pediatric B-Cell ALL: toward safer precision therapy.Frontiers in pharmacology · 2026Review
- Review
- Impact of Pharmacogenetics on High-Dose Methotrexate Toxicity in Pediatric Oncology.Pharmaceutics · 2025Article
- Severe hematologic toxicity after low-dose methotrexate in ectopic pregnancy: role of MTHFR polymorphism and drug interaction - a case report and literature review.Frontiers in pharmacology · 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
- Case report: Hepatotoxicity and nephrotoxicity induced by methotrexate in a paediatric patient, what is the role of precision medicine in 2023?Frontiers in pharmacology · 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
- A Risk Scoring Model for High-Dose Methotrexate-Induced Liver Injury in Children With Acute Lymphoblastic Leukemia Based on Gene Polymorphism Study.Frontiers in pharmacology · 2021Article
- Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The associations between methylenetetrahydrofolate reductase (MTHFR) polymorphism and methotrexate (MTX)-induced toxicities in patients with acute lymphoblastic leukemia (ALL) have been evaluated in various populations, with the results remained conflicting. Therefore, we conducted a meta-analysis by combining available data to derive a more precise estimation of the association. PubMed, Embase, and China National Knowledge Infrastructure were searched until 21 September 2011 to identify eligible studies. A total of 14 studies were included, with all studies investigating MTHFR C677T polymorphism while nine of them investigating MTHFR A1298C polymorphism only. Results suggested that MTHFR C677T polymorphism was associated with significantly increased risk of MTX-induced toxicity, specifically liver toxicity (TT/CT vs. CC: odds ratio (OR) = 1.70, 95 % confidence interval (CI) = 1.05-2.75), myelosuppression (TT vs. CT/CC: OR = 2.82, 95 %CI = 1.25-6.34), oral mucositis (TT/CT vs. CC: OR = 3.68, 95 %CI = 1.73-7.85), gastrointestinal toxicity (TT/CT vs. CC: OR = 2.36, 95 %CI = 1.36-4.11), and skin toxicity (T vs. C: OR = 2.26, 95 %CI = 1.07-4.74). MTHFR A1298C polymorphism was found to be associated with decreased risk of skin toxicity (CC/AC vs. AA: OR = 0.11, 95 %CI = 0.01-0.85). Genotyping of MTHFR polymorphism, C677T particularly, prior to treatment for ALL is likely to be useful with the aim of tailoring MTX therapy and thus reducing the MTX-related toxicities. However, further studies with larger data set and well-designed models are required to validate our findings.
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