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

Hedy Maagdenberg, Natanja Oosterom, Jolanda Zanen, Donato Gemmati, Rachael E. Windsor, Sandra G. Heil, Patricia Esperón, Shakila Jabeen, Guillermo J. Ruiz-Argüelles, Oliver Zolk, Susanne Hoerning, Charlotte Sleurs, Elixabet Lopéz-Lopéz, Mónica Moreno-Galván, Marry M. van den Heuvel-Eibrink, Anke H. Maitland-van der Zee, Bruce C. Carleton

Research output: Contribution to journalReview articlepeer-review

9 Citations (Scopus)

Abstract

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 MTX-induced 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).

Original languageEnglish
Article number103312
JournalCritical Reviews in Oncology/Hematology
Volume161
DOIs
Publication statusPublished - May 2021

Keywords

  • Adult
  • Cancer
  • Gastrointestinal toxicity
  • Methotrexate
  • Mucositis
  • Pediatric
  • Pharmacogenomics

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