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

doi:10.1016/j.critrevonc.2021.103312

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 journal › Review article › peer-review

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 language	English
Pages (from-to)	103312
Journal	Critical Reviews in Oncology/Hematology
Volume	161
DOIs	https://doi.org/10.1016/j.critrevonc.2021.103312
Publication status	Published - 2021
Externally published	Yes

Keywords

Antimetabolites, Antineoplastic/adverse effects
Humans
Methotrexate/adverse effects
Methylenetetrahydrofolate Reductase (NADPH2)/genetics
Mucositis/chemically induced
Neoplasms/drug therapy
Polymorphism, Single Nucleotide

Access to Document

10.1016/j.critrevonc.2021.103312

Cite this

Maagdenberg, H., Oosterom, N., Zanen, J., Gemmati, D., Windsor, R. E., Heil, S. G., Esperón, P., Jabeen, S., Ruiz-Argüelles, G. J., Zolk, O., Hoerning, S., Sleurs, C., Lopéz-Lopéz, E., Moreno-Galván, M., van den Heuvel-Eibrink, M. M., Maitland-van der Zee, A. H., & Carleton, B. C. (2021). Genetic variants associated with methotrexate-induced mucositis in cancer treatment: A systematic review and meta-analysis. Critical Reviews in Oncology/Hematology, 161, 103312. https://doi.org/10.1016/j.critrevonc.2021.103312

@article{8c617003fb1e481b85b2b3d5da922d50,

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

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).",

keywords = "Antimetabolites, Antineoplastic/adverse effects, Humans, Methotrexate/adverse effects, Methylenetetrahydrofolate Reductase (NADPH2)/genetics, Mucositis/chemically induced, Neoplasms/drug therapy, Polymorphism, Single Nucleotide",

author = "Hedy Maagdenberg and Natanja Oosterom and Jolanda Zanen and Donato Gemmati and Windsor, {Rachael E} and Heil, {Sandra G} and Patricia Esper{\'o}n and Shakila Jabeen and Ruiz-Arg{\"u}elles, {Guillermo J} and Oliver Zolk and Susanne Hoerning and Charlotte Sleurs and Elixabet Lop{\'e}z-Lop{\'e}z and M{\'o}nica Moreno-Galv{\'a}n and {van den Heuvel-Eibrink}, {Marry M} and {Maitland-van der Zee}, {Anke H} and Carleton, {Bruce C}",

year = "2021",

doi = "10.1016/j.critrevonc.2021.103312",

language = "English",

volume = "161",

pages = "103312",

journal = "Critical Reviews in Oncology/Hematology",

issn = "1040-8428",

publisher = "Elsevier Ireland Ltd",

}

Maagdenberg, H, Oosterom, N, Zanen, J, Gemmati, D, Windsor, RE, Heil, SG, Esperón, P, Jabeen, S, Ruiz-Argüelles, GJ, Zolk, O, Hoerning, S, Sleurs, C, Lopéz-Lopéz, E, Moreno-Galván, M, van den Heuvel-Eibrink, MM, Maitland-van der Zee, AH & Carleton, BC 2021, 'Genetic variants associated with methotrexate-induced mucositis in cancer treatment: A systematic review and meta-analysis', Critical Reviews in Oncology/Hematology, vol. 161, pp. 103312. https://doi.org/10.1016/j.critrevonc.2021.103312

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

PY - 2021

Y1 - 2021

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 - Antimetabolites, Antineoplastic/adverse effects

KW - Humans

KW - Methotrexate/adverse effects

KW - Methylenetetrahydrofolate Reductase (NADPH2)/genetics

KW - Mucositis/chemically induced

KW - Neoplasms/drug therapy

KW - Polymorphism, Single Nucleotide

U2 - 10.1016/j.critrevonc.2021.103312

DO - 10.1016/j.critrevonc.2021.103312

M3 - Review article

C2 - 33794308

SN - 1040-8428

VL - 161

SP - 103312

JO - Critical Reviews in Oncology/Hematology

JF - Critical Reviews in Oncology/Hematology

ER -

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

Abstract

Keywords

Access to Document

Fingerprint

Cite this