Correlation between gene polymorphism and adverse reactions of high-dose methotrexate in osteosarcoma patients: a systematic review and meta-analysis.

Abstract

OBJECTIVE:

We aimed to provide a reference based on evidence for an individualized clinical medication of high-dose methotrexate (HD-MTX) in osteosarcoma patients by evaluating the effect of gene polymorphism on adverse reactions of HD-MTX usage.

METHODS:

Several databases were combed for research on the association between gene polymorphisms and adverse reactions to HD-MTX up to January 2023. A meta-analysis and/or descriptive analysis on the incidence of HD-MTX-related adverse reactions were conducted by using clinical studies meeting inclusion criteria.

RESULTS:

Twelve studies involving 889 patients were included. There were 8, 6, 5, and 4 studies related to MTHFR C677T, MTHFR A1298C, RFC1 G80A, and MDR1 C3435T polymorphisms, respectively. The results of the meta-analysis showed that the MTHFR C677T polymorphism was associated with G3-4 hepatotoxicity, G3-4 nephrotoxicity, G3-4 gastrointestinal toxicity, and G3-4 mucositis under the recessive genetic model (MM vs. Mm/mm). Limited research showed that MTHFR C677T was associated with G3-4 nephrotoxicity in the allelic genetic model (M vs. m). MTHFR A1298C polymorphism was associated with a decreased risk of adverse reactions to HD-MTX usage, without statistical significance. This review's descriptive analysis showed no significant correlation between the RFC1 G80A, and MDR1 C3435T polymorphism and adverse reactions of HD-MTX.

CONCLUSION:

The MTHFR C677T mutation may enhance the risk of HD-MTX adverse reactions in osteosarcoma patients. Existing studies have not found a significant correlation between the MTHFR A1298C, RFC1 G80A, and MDR1 C3435T polymorphism and adverse reactions caused by HD-MTX. Lastly, this conclusion was limited because of few studies.

• Authors: Ben Liu, Gang Liu, Binbin Liu, Yao Guo, Ningning Peng, Tiejun Li
• Journal: World journal of surgical oncology (World J Surg Oncol) Vol. 22 Issue 1 Pg. 19 (Jan 11 2024) ISSN: 1477-7819 [Electronic] England
• PMID: 38212758 (Publication Type: Meta-Analysis, Systematic Review, Journal Article)
• Copyright: © 2024. The Author(s).

Chemical References

• Methotrexate
• Methylenetetrahydrofolate Reductase (NADPH2)

Topics

• Humans
• Methotrexate (adverse effects)
• Polymorphism, Genetic
• Alleles
• Methylenetetrahydrofolate Reductase (NADPH2) (genetics)
• Osteosarcoma (drug therapy, genetics)
• Polymorphism, Single Nucleotide
• Genotype