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

Authors
  • Maagdenberg, Hedy;
  • Oosterom, Natanja;
  • Zanen, Jolanda;
  • Gemmati, Donato;
  • Windsor, Rachael E;
  • Heil, Sandra G;
  • Esperon, Patricia;
  • Jabeen, Shakila;
  • Ruiz-Arguelles, Guillermo J;
  • Zolk, Oliver;
  • Hoerning, Susanne;
  • Sleurs, Charlotte; 85069;
  • Lopez-Lopez, Elixabet;
  • Moreno-Galvan, Monica;
  • van den Heuvel-Eibrink, Marry M;
  • van der Zee, Anke H;
  • Carleton, Bruce C;
Publication Date
May 01, 2021
Source
Lirias
Keywords
Language
English
License
Unknown
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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). / status: published

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