Genetic variants associated with methotrexate-induced mucositis in cancer treatment: A systematic review and meta-analysis

Methotrexate (MTX), an important chemotherapeutic agent, is often accompanied with mucositis. The occurrence and severity are unpredictable and show large interindividual variability. In this study, we review and meta-analyze previously studied genetic variants in relation to MTX-induced mucositis. We conducted a systematic search in Medline and Embase. We included genetic association studies of MTXinduced mucositis in cancer patients. A meta-analysis was conducted for single nucleotide polymorphisms (SNPs) for which at least two studies found a statistically significant association. A total of 34 SNPs were associated with mucositis in at least one study of the 57 included studies. Two of the seven SNPs included in our meta-analysis were statistically significantly associated with mucositis: MTHFR c.677C > T (recessive, grade >3 vs grade 0-2, OR 2.53, 95 %CI [1.48-4.32], False Discovery Rate[FDR]corrected p-value 0.011) and MTRR c.66A > G (overdominant, grade >1 vs grade 0, OR 2.08, 95 %CI [1.16-3.73], FDR-corrected p-value 0.042).

Automated summary

Methotrexate-induced mucositis varies greatly among individuals, and genetic variants such as MTHFR c.677C > T and MTRR c.66A > G have been found to have statistically significant associations with the occurrence of mucositis. Further research in this area may help in predicting and managing this common side effect of MTX treatment.