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Polymorphisms of drug-metabolizing enzymes and risk of childhood acute lymphoblastic leukemia

S Pakakasama1, E Mukda, W Sasanakul

  • 1Department of Pediatrics, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand. rasam@mhidol.ac.th

American Journal of Hematology
|June 28, 2005
PubMed

Insights

The GSTM1 null genotype may increase the risk of childhood acute lymphoblastic leukemia (ALL). This finding suggests a potential genetic susceptibility in childhood cancer risk among the Thai population.

Area of Science:

  • Pharmacogenetics
  • Cancer Epidemiology
  • Molecular Biology

Background:

  • Phase I and II enzymes are crucial for drug and xenobiotic metabolism.
  • Single-nucleotide polymorphisms (SNPs) in these enzymes can affect their function and expression.
  • Genetic susceptibility and environmental factors are implicated in cancer etiology.

Purpose of the Study:

  • To investigate the association between polymorphisms in drug-metabolizing enzymes and the risk of childhood acute lymphoblastic leukemia (ALL).
  • To explore the potential role of genetic variations in enzymes like CYP1A1, CYP3A4, CYP3A5, GSTM1, and GSTT1 in childhood ALL.

Main Methods:

  • Genotyping of CYP 1A1, CYP 3A4*1B, CYP 3A5*3, CYP 3A5*6, GSTM1, and GSTT1 polymorphisms using PCR-RFLP.
  • Comparison of allele and genotype frequencies between 107 children with ALL and 320 healthy controls.
  • Statistical analysis to determine odds ratios and confidence intervals for identified polymorphisms.

Main Results:

  • No significant differences in allele frequencies were observed for CYP 1A1 polymorphisms between ALL cases and controls.
  • CYP 3A4*1B and CYP 3A5 polymorphisms did not show a statistically significant association with childhood ALL risk.
  • The GSTM1 null genotype was significantly more frequent in children with ALL (OR 1.7; 95% CI, 1.0, 2.7), suggesting an increased risk.

Conclusions:

  • The GSTM1 null genotype is associated with an increased risk of childhood ALL in the studied Thai population.
  • These findings highlight the potential role of specific genetic polymorphisms in drug-metabolizing enzymes in the susceptibility to childhood leukemia.
  • Further research is warranted to elucidate the precise mechanisms linking GSTM1 null genotype to childhood ALL.

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