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

被引：9

作者：

Maagdenberg, Hedy ^{[1
,2
,3
,4
]}

Oosterom, Natanja ^{[5
,6
]}

Zanen, Jolanda ^{[2
,7
]}

Gemmati, Donato ^{[8
]}

Windsor, Rachael E. ^{[9
]}

Heil, Sandra G. ^{[6
]}

Esperon, Patricia ^{[10
]}

Jabeen, Shakila ^{[11
,12
]}

Ruiz-Arguelles, Guillermo J. ^{[13
,14
]}

Zolk, Oliver ^{[15
]}

Hoerning, Susanne ^{[16
]}

Sleurs, Charlotte ^{[17
]}

Lopez-Lopez, Elixabet ^{[18
,19
]}

Moreno-Galvan, Monica ^{[20
,21
]}

van den Heuvel-Eibrink, Marry M. ^{[5
]}

van der Zee, Anke H. ^{[4
,5
]}

Carleton, Bruce C. ^{[1
,2
,3
]}

机构：

[1] BC Childrens Hosp, Res Inst, Vancouver, BC, Canada

[2] Univ British Columbia, Fac Med, Dept Pediat, Div Translat Therapeut, Vancouver, BC, Canada

[3] BC Childrens Hosp, Pharmaceut Outcomes Programme, Vancouver, BC, Canada

[4] Univ Amsterdam, Amsterdam Univ Med Ctr, Dept Resp Med, Amsterdam, Netherlands

[5] Princess Maxima Ctr Pediat Oncol, Utrecht, Netherlands

[6] Erasmus MC Univ Med Ctr Rotterdam, Dept Clin Chem, Rotterdam, Netherlands

[7] Univ Utrecht, Dept Pharmaceut Sci, Utrecht, Netherlands

[8] Univ Ferrara, Ctr Thrombosis & Hemostasis, Dept Translat Med, Ferrara, Italy

[9] Univ Coll London Hosp NHS Fdn Trust, Children & Young Peoples Canc Serv, London, England

[10] Univ Republica, Fac Quim, Dept Bioquim Clin, Lab Biol Mol, Montevideo, Uruguay

[11] Akershus Univ Hosp, Div Med, Dept Clin Mol Biol EpiGen, Lorenskog, Norway

[12] Oslo Univ Hosp, Inst Canc Res, Dept Canc Genet, Oslo, Norway

[13] Clin Ruiz Puebla, Ctr Hematol & Med Interna, Puebla, Mexico

[14] Clin Ruiz Puebla, Lab Clin Puebla, Puebla, Mexico

[15] Univ Hosp, Inst Pharmacol Nat Prod & Clin Pharmacol, Ulm, Germany

[16] Univ Hosp Children & Adolescents, Dept Pediat Oncol & Immunol, Erlangen, Germany

[17] Katholieke Univ Leuven, Dept Pediat Hematooncol, Leuven, Belgium

[18] Univ Basque Country UPV EHU, Dept Genet Phys Anthropol & Anim Physiol, Fac Med & Nursing, Leioa, Spain

[19] BioCruces Bizkaia Hlth Res Inst, Baracaldo, Spain

[20] Hosp Infantil Mexico Dr Federico Gomez, Dept Hematooncol, Mexico City, DF, Mexico

[21] CENAPRECE SSA, Soc Mexicana Salud Publ, Mexico City, DF, Mexico

来源：

CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY | 2021年 / 161卷

关键词：

Methotrexate; Mucositis; Gastrointestinal toxicity; Pharmacogenomics; Pediatric; Adult; Cancer; HIGH-DOSE METHOTREXATE; ACUTE LYMPHOBLASTIC-LEUKEMIA; METHYLENETETRAHYDROFOLATE REDUCTASE C677T; INDUCED ORAL MUCOSITIS; MTHFR; 677C-GREATER-THAN-T; INDUCED TOXICITY; FOLATE PATHWAY; RISK-FACTOR; POLYMORPHISMS; CHILDHOOD;

D O I：

10.1016/j.critrevonc.2021.103312

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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 MTXinduced 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).

引用

页数：12

共 75 条

[71] Influence of Folate-Related Gene Polymorphisms on High-Dose Methotrexate-Related Toxicity and Prognosis in Turkish Children with Acute Lymphoblastic Leukemia [J].