AUTHOR=Han Jian , Liu Lu , Meng Li , Guo Huan , Zhang Jin , Han Zhi-Qiang , Hong Zhen-Ya 

TITLE=Effect of Polymorphisms of ABCB1 and MTHFR on Methotrexate-Related Toxicities in Adults With Hematological Malignancies

JOURNAL=Frontiers in Oncology

VOLUME=11

YEAR=2021

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.759805

DOI=10.3389/fonc.2021.759805

ISSN=2234-943X

ABSTRACT=<p>Study of the association between single nucleotide polymorphisms (SNPs) of methotrexate (MTX) pathway genes and MTX-related toxicity in the treatment of hematological malignancies is popular. Here, we studied the association between SNPs of MTHFR and ABCB1 and MTX-related toxicity in 157 adult Chinese patients diagnosed with hematological malignancies. Patients were genotyped for MTHFR rs1801131, MTHFR rs1801133, and ABCB1 rs1045642 by fluorescence <italic>in situ</italic> hybridization. Patients with MTHFR rs1801133T allele had a significantly higher risk of hematopoietic toxicity compared with those with CC genotype (p=0.003). With respect to MTHFR rs1801131, patients with CC and AC genotypes had significantly lower frequency of hematopoietic toxicity than patients with AA genotype (p=0.044). In conclusion, we identified an important influence of the SNPs of ABCB1 and MTHFR on MTX-related hematopoietic toxicity in adults with hematological malignancies. To optimize high-dose (HD)-MTX therapy and reduce related hematopoietic toxicity, it is necessary to detect the SNPs of MTHFR and ABCB1 before initiating HD-MTX and deciding the optimal dose of MTX and duration of leucovorin rescue, according to genetic tests and disease type in adults with hematological malignancies.</p>