MTHFR 677 C>T- and 1298 A>C-related adverse effects in 5-fluorouracil-based chemotherapy in the Asian population: a systematic review and meta-analysis

This study was conducted to delineate the correlation between polymorphisms in methylenetetrahydrofolate reductase (MTHFR) and toxicity of 5-fluorouracil (5-FU)-based chemotherapy regimens in the Asian demographic.

A systematic review across PubMed, Embase, and the Cochrane Library databases from inception up to November 23, 2023, was performed. We employed standardized methods for data extraction and quality evaluation, followed by a meta-analysis to ascertain odds ratios and 95% confidence intervals associated with chemotherapy-induced toxicity.

This systematic review and meta-analysis integrated results from nine studies, encompassing a total of 1882 patients with cancer. Notably, there was a pronounced increase in the risk of severe haematological toxicity (notably neutropenia) and gastrointestinal toxicity (specifically diarrhea) among patients harbouring the MTHFR 677 C>T variant. Conversely, the relationship between the MTHFR 1298 A>C polymorph and chemotherapy-induced toxicity remained ambiguous. The integrity of the results was confirmed through publication bias and sensitivity analyses, demonstrating the robustness and reliability of the findings.

A link exists between MTHFR 677 C>T and heightened toxicity risk in Asian patients undergoing 5-FU-based chemotherapy.