Mutation screening and association study of the folylpolyglutamate synthetase (FPGS) gene with susceptibility to childhood acute lymphoblastic leukemia

Duangjai Piwkham, Teerapong Siriboonpiputtana, Joke Beuten, Samart Pakakasama, Jonathan A Gelfond, Karan Paisooksantivatana, Gail Tomlinson, Budsaba Rerkamnuaychoke

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

Background: Folylpolyglutamate synthetase (FPGS), an important enzyme in the folate metabolic pathway, plays a central role in intracellular accumulation of folate and antifolate in several mammalian cell types. Loss of FPGS activity results in decreased cellular levels of antifolates and consequently to polyglutamatable antifolates in acute lymphoblastic leukemia (ALL). Materials and Methods: During May 1997 and December 2003, 134 children diagnosed with ALL were recruited from one hospital in Thailand. We performed a mutation analysis in the coding regions of the FPGS gene and the association between single nucleotide polymorphisms (SNPs) within FPGS in a case-control sample of childhood ALL patients. Mutation screening was conducted by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) and subsequently with direct sequencing (n=72). Association analysis between common FPGS variants and ALL risk was done in 98 childhood ALL cases and 95 healthy volunteers recruited as controls. Results: Seven SNPs in the FPGS coding region were identified by mutation analysis, 3 of which (IVS13+55C > T, g.1297T > G, and g.1508C > T) were recognized as novel SNPs. Association analysis revealed 3 of 6 SNPs to confer significant increase in ALL risk these being rs7039798 (p= 0.014, OR=2.14), rs1544105 (p=0.010, OR= 2.24), and rs10106 (p=0.026, OR= 1.99). Conclusions: These findings suggested that common genetic polymorphisms in the FPGS coding region including rs7039789, rs1544105, and rs10106 are significantly associated with increased ALL risk in Thai children.

Original languageEnglish (US)
Pages (from-to)4727-4732
Number of pages6
JournalAsian Pacific Journal of Cancer Prevention
Volume16
Issue number11
DOIs
StatePublished - 2015

Keywords

  • Acute lymphoblastic leukemia
  • Folylpolyglutamate synthetase
  • Single nucleotide polymorphism

ASJC Scopus subject areas

  • Oncology
  • Cancer Research
  • Public Health, Environmental and Occupational Health
  • Epidemiology

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