MTHFR gene polymorphisms and methotrexate toxicity in adult patients with hematological malignancies: a meta-analysis.
MTHFR gene polymorphisms has been shown to be associated with methotrexate (MTX) toxicity in adult hematological malignancies; however, the results remain inconclusive.



To examine the role of common MTHFR variants in MTX toxicity prediction, we performed a meta-analysis via identifying relevant studies for quantitative data pooling.



Our results showed a significant association between MTHFR C677T polymorphism and increased risk of MTX-induced all-grade (grade 1-4) and severe (grade 3-4) hepatic and gastrointestinal toxicities in Caucasian independent of MTX dosage. MTHFR 677T allele increased risk of severe mucositis and all-grade hematological toxicity. MTHFR A1298C polymorphism was not significantly associated with hepatic and hematological toxicity, whereas perhaps having a protective effect on mucositis and gastrointestinal toxicity.



MTHFR C677T polymorphism may be a good predictor for MTX toxicity in adult hematological malignancies.
Department of Pharmacy, Beijing Hospital, No. 1 Dahua Road, Dong Dan, Beijing 100730, P. R. China.
Ming
M
Zhao
Department of Pharmacy, Beijing Hospital, No. 1 Dahua Road, Dong Dan, Beijing 100730, P. R. China.
Liang
L
Liang
Department of Pharmacy, Beijing Hospital, No. 1 Dahua Road, Dong Dan, Beijing 100730, P. R. China.
Liwei
L
Ji
Department of Pharmacy, Beijing Hospital, No. 1 Dahua Road, Dong Dan, Beijing 100730, P. R. China.
Di
D
Chen
Department of Pharmacy, Beijing Hospital, No. 1 Dahua Road, Dong Dan, Beijing 100730, P. R. China.
Yatong
Y
Zhang
Department of Pharmacy, Beijing Hospital, No. 1 Dahua Road, Dong Dan, Beijing 100730, P. R. China.
Yuanchao
Y
Zhu
Department of Morphology, Surgery & Experimental Medicine, University of Ferrara, Ferrara 44121, Italy.
Alessia
A
Ongaro
D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects* / Q000627:therapeutic use*; D019337:Hematologic Neoplasms / Q000150:complications* / Q000188:drug therapy* / Q000235:genetics; D006801:Humans; D008727:Methotrexate / Q000009:adverse effects* / Q000627:therapeutic use*; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics
D000964:Antimetabolites, Antineoplastic; C573423:MTHFR protein, human; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D008727:Methotrexate
MTHFR; adult; hematological malignancy; polymorphism; toxicity