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Impact of methylenetetrahydrofolate reductase (MTHFR) polymorphisms on methotrexate-induced toxicities in acute

Lin Yang1, Xin Hu, Luhang Xu

  • 1Department of Pharmacy, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China. hxydyl@yeah.net

Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine
|April 25, 2012
PubMed

Insights

Methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism increases methotrexate toxicity risk in acute lymphoblastic leukemia (ALL) patients. Genotyping MTHFR may help personalize ALL treatment and reduce adverse effects.

Area of Science:

  • Pharmacogenomics
  • Oncology
  • Genetics

Background:

  • Methotrexate (MTX) is a key drug in acute lymphoblastic leukemia (ALL) treatment.
  • Methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms may influence MTX efficacy and toxicity.
  • Existing research on MTHFR polymorphisms and MTX-induced toxicities in ALL yields conflicting results.

Purpose of the Study:

  • To conduct a meta-analysis to clarify the association between MTHFR polymorphisms and MTX-induced toxicities in ALL patients.
  • To provide a more precise estimation of these associations by combining available data.

Main Methods:

  • Systematic literature search of PubMed, Embase, and China National Knowledge Infrastructure databases until September 21, 2011.
  • Inclusion of 14 studies evaluating MTHFR C677T and/or MTHFR A1298C polymorphisms.
  • Statistical analysis using odds ratios (OR) and 95% confidence intervals (CI) to assess toxicity risks.

Main Results:

  • MTHFR C677T polymorphism was significantly associated with increased risks of liver toxicity, myelosuppression, oral mucositis, gastrointestinal toxicity, and skin toxicity.
  • MTHFR A1298C polymorphism was linked to a decreased risk of skin toxicity.
  • Specific ORs and CIs were reported for various genotypes and toxicity types.

Conclusions:

  • MTHFR C677T polymorphism is a significant risk factor for MTX-induced toxicities in ALL patients.
  • Genotyping MTHFR, particularly C677T, before ALL treatment could aid in tailoring MTX therapy.
  • Further large-scale, well-designed studies are needed to validate these findings.

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