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Genetic variants associated with methotrexate-induced mucositis in cancer treatment: A systematic review and
Hedy Maagdenberg1, Natanja Oosterom2, Jolanda Zanen3
1BC Children's Hospital Research Institute, Vancouver, BC, Canada; Division of Translational Therapeutics, Department of Pediatrics, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada; Pharmaceutical Outcomes Programme, BC Children's Hospital, Vancouver, BC, Canada; Department of Respiratory Medicine, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
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).
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