ATIC Gene Polymorphism and Histologic Response to Chemotherapy in Pediatric Osteosarcoma

J Pediatr Hematol Oncol. 2017 Jul;39(5):e270-e274. doi: 10.1097/MPH.0000000000000802.


Accumulating evidence indicates that polymorphisms in folate pathway genes play a role in response to methotrexate (MTX) treatment in various diseases. This study explored the influence of these genetic polymorphisms on treatment outcome in pediatric osteosarcoma. Blood and tissue samples from 48 osteosarcoma patients were obtained, and the following polymorphisms were analyzed; SLC19A1 80G>A, DHFR 829C>T, MTHFR 677C>T, MTHFR 1298A>C, and ATIC 347C>G. We evaluated associations between these candidate gene polymorphisms and treatment outcome, including histologic response and event-free and overall survival, of patients treated with high-dose MTX. Patients with ATIC 347C>G exhibited a good histologic response to chemotherapy (odds ratio, 0.13; 95% confidence interval, 0.017-0.978; P=0.048). However, none of these single nucleotide polymorphisms we examined affected event-free survival or overall survival rates of the patients. Even though the role of single nucleotide polymorphisms of ATIC in chemotherapy-induced tumor necrosis has not been investigated yet, the ATIC 347C>G polymorphism may influence the levels of adenosine after MTX treatment, which may affect the histologic response of osteosarcoma. This relationship warrants validation in a larger, prospective cohort study.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine / blood
  • Adolescent
  • Antineoplastic Agents / therapeutic use
  • Child
  • Child, Preschool
  • Disease-Free Survival
  • Female
  • Humans
  • Hydroxymethyl and Formyl Transferases / genetics*
  • Male
  • Methotrexate / therapeutic use
  • Methylenetetrahydrofolate Reductase (NADPH2) / genetics
  • Multienzyme Complexes / genetics*
  • Nucleotide Deaminases / genetics*
  • Osteosarcoma / drug therapy*
  • Osteosarcoma / genetics*
  • Osteosarcoma / mortality
  • Polymorphism, Single Nucleotide*
  • Reduced Folate Carrier Protein / genetics
  • Survival Rate
  • Tetrahydrofolate Dehydrogenase / genetics


  • Antineoplastic Agents
  • Multienzyme Complexes
  • Reduced Folate Carrier Protein
  • SLC19A1 protein, human
  • inosine monophosphate synthase
  • Methylenetetrahydrofolate Reductase (NADPH2)
  • Tetrahydrofolate Dehydrogenase
  • Hydroxymethyl and Formyl Transferases
  • Nucleotide Deaminases
  • Adenosine
  • Methotrexate