Asian Pacific Journal of Cancer Prevention

  • 제13권7호
  • /
  • Pages.3461-3464
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  • 2012
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  • 1513-7368(pISSN)
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  • 2476-762X(eISSN)
아시아태평양암예방학회 (Asian Pacific Journal of Cancer Prevention)
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Association Between Polymorphisms of Dihydrofolate Reductase and Gamma Glutamyl Hydrolase Genes and Toxicity of High Dose Methotrexate in Children with Acute Lymphoblastic Leukemia

  • Koomdee, Napatrupron (Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University) ;
  • Hongeng, Suradej (Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University) ;
  • Apibal, Suntaree (Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University) ;
  • Pakakasama, Samart (Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University)
  • 발행 : 2012.07.31
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초록

Methotrexate (MTX) is an important drug for the treatment of childhood acute lymphoblastic leukemia (ALL). However, related toxicity occurs in many organs which may cause interruption of treatment, morbidity, and mortality. Single nucleotide polymorphisms (SNPs) of dihydrofolate reductase (DHFR) and gamma glutamyl hydrolase (GGH) are known to alter their enzymatic activity and thus affect the metabolism of MTX and influence the effectiveness. Therefore, we hypothesized that genetic variations of DHFR and GGH genes may influence the risk of toxicity after high dose MTX. The study population comprised of 105 children with ALL who were treated according to the modified St Jude Total XV protocol. The patients received 2.5 or $5g/m^2$ of MTX for 5 doses during the consolidation phase. Genotyping of DHFR 829C>T and GGH-401C>T was performed using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The GGH-401CT and TT genotypes were associated with increased risk of leukopenia and thrombocytopenia after high dose MTX (OR 2.97, 95%CI; 1.24-7.13 and OR 4.02, 95%CI; 1.58-10.26). DHFR 829C>T was not associated with toxicity. In conclusion, the GGH-401CT and TT genotypes were found to increase the risk of severe leukopenia and thrombocytopenia after exposure to high dose MTX for childhood ALL therapy.

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참고문헌

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피인용 문헌

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  2. Influence of genetic polymorphisms of FPGS, GGH, and MTHFR on serum methotrexate levels in Chinese children with acute lymphoblastic leukemia vol.74, pp.2, 2014, https://doi.org/10.1007/s00280-014-2507-8
  3. γ-Glutamyl hydrolase modulation significantly influences global and gene-specific DNA methylation and gene expression in human colon and breast cancer cells vol.10, pp.1, 2015, https://doi.org/10.1007/s12263-014-0444-0
  4. Gene polymorphisms in the folate metabolism and their association with MTX-related adverse events in the treatment of ALL vol.36, pp.7, 2015, https://doi.org/10.1007/s13277-015-3602-0
  5. Dihydrofolate Reductase Genetic Polymorphisms Affect Methotrexate Dose Requirements in Pediatric Patients With Acute Lymphoblastic Leukemia on Maintenance Therapy vol.39, pp.8, 2017, https://doi.org/10.1097/MPH.0000000000000908
  6. Genetic markers in methotrexate treatments pp.1473-1150, 2018, https://doi.org/10.1038/s41397-018-0047-z
  7. SNPs affecting the clinical outcomes of regularly used immunosuppressants vol.19, pp.5, 2018, https://doi.org/10.2217/pgs-2017-0182