TY - JOUR
T1 - Genetic variants associated with methotrexate-induced mucositis in cancer treatment
T2 - A systematic review and meta-analysis
AU - Maagdenberg, Hedy
AU - Oosterom, Natanja
AU - Zanen, Jolanda
AU - Gemmati, Donato
AU - Windsor, Rachael E.
AU - Heil, Sandra G.
AU - Esperón, Patricia
AU - Jabeen, Shakila
AU - Ruiz-Argüelles, Guillermo J.
AU - Zolk, Oliver
AU - Hoerning, Susanne
AU - Sleurs, Charlotte
AU - Lopéz-Lopéz, Elixabet
AU - Moreno-Galván, Mónica
AU - van den Heuvel-Eibrink, Marry M.
AU - Maitland-van der Zee, Anke H.
AU - Carleton, Bruce C.
N1 - Publisher Copyright:
© 2021 Elsevier B.V.
PY - 2021/5
Y1 - 2021/5
N2 - 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).
AB - 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).
KW - Adult
KW - Cancer
KW - Gastrointestinal toxicity
KW - Methotrexate
KW - Mucositis
KW - Pediatric
KW - Pharmacogenomics
UR - http://www.scopus.com/inward/record.url?scp=85105515984&partnerID=8YFLogxK
U2 - 10.1016/j.critrevonc.2021.103312
DO - 10.1016/j.critrevonc.2021.103312
M3 - Review article
C2 - 33794308
AN - SCOPUS:85105515984
SN - 1040-8428
VL - 161
JO - Critical Reviews in Oncology/Hematology
JF - Critical Reviews in Oncology/Hematology
M1 - 103312
ER -