Influence of MTHFR and RFC1 Polymorphisms on Toxicities during maintenance chemotherapy for childhood acute lymphoblastic leukemia or lymphoma

被引：47

作者：

Shimasaki, Noriko ^{[1
]}

Mori, Tetyuya ^{[1
,3
]}

Torii, Chiharu ^{[1
]}

Sato, Reiko ^{[2
]}

Shimada, Hiroyuki ^{[1
]}

Tanigatvara, Yusuke ^{[2
]}

Kosaki, Kenjiro ^{[1
]}

Takahashi, Takao ^{[1
]}

机构：

[1] Keio Univ, Dept Pediat, Sch Med, Shinjuku Ku, Tokyo 1608582, Japan

[2] Keio Univ, Dept Pharm, Sch Med, Shinjuku Ku, Tokyo 1608582, Japan

[3] Natl Ctr Child Hlth & Dev, Dept Pediat Oncol, Tokyo, Japan

来源：

JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY | 2008年 / 30卷 / 05期

关键词：

polymorphism; maintenance chemotherapy; methylenetetrahydrofolate reductase (MTHFR); reduced folate carrier 1 (RFC1);

D O I：

10.1097/MPH.0b013e318165b25d

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

We investigated preliminarily whether methylenetetrahydrofolate reductase (MTHFR) 677C/T or reduced folate carrier (RFC1) 80G/A polymorphisms were associated with toxicities during maintenance chemotherapy with mercaptopurine (6MP) and methotrexate (MTX) in children with acute lymphoblastic leukemia or lymphoblastic lymphoma. The clinical records of 20 children (2 to 15-y old) who had received maintenance chemotherapy were reviewed retrospectively and their genomic DNA was genotyped to identify polymorphisms at MTHFR 677C/T, RFC1 80G/A, and thiopurine methyltransferase 719A/G. Maintenance chemotherapy with 6MP and MTX was repeated on a weekly basis, and any week during which 6MP and/or MTX dosing was withheld was counted as an interrupted episode. Associations between the risk of interruptions and polymorphisms Were Studied using a generalized estimating equation analysis. Patients with an increasing number of T alleles at MTHFR 677C/T experienced interruptions in both 6MP (P < 0.01) and MTX (P = 0.03) more frequently. Patients with an increasing number of A alleles at RFC1 80G/A experienced interruptions in 6MP (P = 0.04) more frequently. This preliminary study does not prove but suggests that MTHFR 677C/T and RFC1 80G/A polymorphisms may serve as predictors of toxicity during maintenance chemotherapy.

引用

页码：347 / 352

页数：6

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