A systematic review and meta-analysis of MTHFR polymorphisms in methotrexate toxicity prediction in pediatric acute lymphoblastic leukemia

被引:0
作者
E Lopez-Lopez
I Martin-Guerrero
J Ballesteros
A Garcia-Orad
机构
[1] Physic Anthropology and Animal Physiology,Department of Genetics
[2] Faculty of Medicine and Dentistry,Department of Neurosciences
[3] University of the Basque Country,undefined
[4] University of the Basque Country,undefined
[5] CIBERSAM,undefined
来源
The Pharmacogenomics Journal | 2013年 / 13卷
关键词
pharmacogenetics; polymorphism; methotrexate; MTHFR; acute lymphoblastic leukemia; toxicity;
D O I
暂无
中图分类号
学科分类号
摘要
Methotrexate (MTX) is an important component of therapy used to treat childhood acute lymphoblastic leukemia (ALL). Two single-nucleotide polymorphisms (SNPs) in the methylenetetrahydrofolate reductase (MTHFR) gene, C677T and A1298C, affect MTHFR activity. A large body of studies has investigated the potential role of MTHFR SNPs in MTX toxicity in pediatric ALL. However, the results are controversial. In this review and meta-analysis, we critically evaluate the relationship between the C677T and A1298C polymorphisms of MTHFR and MTX toxicity in pediatric ALL. The majority of published reports do not find associations between MTHFR polymorphisms and toxicity in pediatric ALL. When associations are reported, often the results are contradictory to each other. The meta-analysis confirms a lack of association. In conclusion, MTHFR, C677T and A1298C polymorphisms do not seem to be good markers of MTX-related toxicity in pediatric ALL.
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页码:498 / 506
页数:8
相关论文
共 192 条
[1]  
Koppen IJ(2010)Folate related gene polymorphisms and susceptibility to develop childhood acute lymphoblastic leukaemia Br J Haematol 148 3-14
[2]  
Hermans FJ(2010)Childhood cancer survival: a report from the United Kingdom Childhood Cancer Study Cancer Epidemiol 34 659-666
[3]  
Kaspers GJ(2008)Acute lymphoblastic leukaemia Lancet 371 1030-1043
[4]  
Johnston WT(2007)Genetic polymorphisms associated with adverse events and elimination of methotrexate in childhood acute lymphoblastic leukemia and malignant lymphoma J Hum Genet 52 166-171
[5]  
Lightfoot TJ(1996)Intrinsic and acquired resistance to methotrexate in acute leukemia N Engl J Med 335 1041-1048
[6]  
Simpson J(2004)Pharmacogenetics of methotrexate Pharmacogenomics 5 819-834
[7]  
Roman E(2006)Prognostic significance of multidrug resistance-related proteins in childhood acute lymphoblastic leukaemia Eur J Cancer 42 295-309
[8]  
Pui CH(2009)Germline genetic variation in an organic anion transporter polypeptide associated with methotrexate pharmacokinetics and clinical effects J Clin Oncol 27 5972-5978
[9]  
Robison LL(2001)LST-2, a human liver-specific organic anion transporter, determines methotrexate sensitivity in gastrointestinal cancers Gastroenterology 120 1689-1699
[10]  
Look AT(2009)C677T and A1298C MTHFR polymorphisms, a challenge for antifolate and fluoropyrimidine-based therapy personalisation Eur J Cancer 45 1333-1351