TY - JOUR
T1 - Influence of MTHFR and RFC1 polymorphisms on toxicities during maintenance chemotherapy for childhood acute lymphoblastic leukemia or lymphoma
AU - Shimasaki, Noriko
AU - Mori, Tetsuya
AU - Torii, Chiharu
AU - Sato, Reiko
AU - Shimada, Hiroyuki
AU - Tanigawara, Yusuke
AU - Kosaki, Kenjiro
AU - Takahashi, Takao
PY - 2008/5/1
Y1 - 2008/5/1
N2 - We investigated preliminarily whether methylenetetrahydrofolate reductase (MTHFR) 677C/T or reduced folate carrier 1 (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.
AB - We investigated preliminarily whether methylenetetrahydrofolate reductase (MTHFR) 677C/T or reduced folate carrier 1 (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.
KW - Maintenance chemotherapy
KW - Methylenetetrahydrofolate reductase (MTHFR)
KW - Polymorphism
KW - Reduced folate carrier 1 (RFC1)
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U2 - 10.1097/MPH.0b013e318165b25d
DO - 10.1097/MPH.0b013e318165b25d
M3 - Article
C2 - 18458567
AN - SCOPUS:43149111567
SN - 1077-4114
VL - 30
SP - 347
EP - 352
JO - Journal of Pediatric Hematology/Oncology
JF - Journal of Pediatric Hematology/Oncology
IS - 5
ER -