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Identifying DNA Mutations in Purified Hematopoietic Stem/Progenitor Cells
Published on: February 24, 2014
MTHFR gene polymorphisms and methotrexate toxicity in adult patients with hematological malignancies: a meta-analysis
Ming Zhao1, Liang Liang1, Liwei Ji1
1Department of Pharmacy, Beijing Hospital, No. 1 Dahua Road, Dong Dan, Beijing 100730, P. R. China.
Background:
MTHFR gene polymorphisms has been shown to be associated with methotrexate (MTX) toxicity in adult hematological malignancies; however, the results remain inconclusive.
Materials & Methods:
To examine the role of common MTHFR variants in MTX toxicity prediction, we performed a meta-analysis via identifying relevant studies for quantitative data pooling.
Results:
Our results showed a significant association between MTHFR C677T polymorphism and increased risk of MTX-induced all-grade (grade 1-4) and severe (grade 3-4) hepatic and gastrointestinal toxicities in Caucasian independent of MTX dosage. MTHFR 677T allele increased risk of severe mucositis and all-grade hematological toxicity. MTHFR A1298C polymorphism was not significantly associated with hepatic and hematological toxicity, whereas perhaps having a protective effect on mucositis and gastrointestinal toxicity.
Conclusion:
MTHFR C677T polymorphism may be a good predictor for MTX toxicity in adult hematological malignancies.
Insights
The methylenetetrahydrofolate reductase (MTHFR) C677T gene variant is linked to increased methotrexate toxicity in adult hematological cancers. This finding may help predict adverse events in patients undergoing treatment.
Area of Science:
- Genetics and Genomics
- Pharmacogenomics
- Oncology
Background:
- Methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms are investigated for their association with methotrexate (MTX) toxicity in adult hematological malignancies.
- Previous research findings on this association remain inconclusive, necessitating further investigation.
Purpose of the Study:
- To evaluate the predictive role of common MTHFR gene variants in methotrexate toxicity.
- To pool quantitative data from relevant studies through a meta-analysis.
Main Methods:
- A meta-analysis was conducted to identify and pool quantitative data from studies examining MTHFR variants and MTX toxicity.
- Focus was placed on common MTHFR polymorphisms, specifically C677T and A1298C.
Main Results:
- The MTHFR C677T polymorphism showed a significant association with an increased risk of all-grade and severe hepatic and gastrointestinal toxicities induced by MTX in Caucasian patients, irrespective of MTX dosage.
- The MTHFR 677T allele was linked to a higher risk of severe mucositis and all-grade hematological toxicity.
- The MTHFR A1298C polymorphism did not show a significant association with hepatic or hematological toxicity but may offer a protective effect against mucositis and gastrointestinal toxicity.
Conclusions:
- The MTHFR C677T polymorphism may serve as a valuable predictor for methotrexate toxicity in adult patients with hematological malignancies.
- Further research can explore the clinical utility of MTHFR genotyping for personalized MTX treatment strategies.
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