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GSTM1 and codon 72 P53 polymorphism in multiple myeloma

Manoela M Ortega1, Helen N Honma, Lair Zambon

  • 1Department of Internal Medicine, Faculty of Medical Sciences, State University of Campinas, Campinas, São Paulo, Brazil.

Annals of Hematology
|July 27, 2007
PubMed

Insights

Genetic variations in GSTM1, GSTT1, and P53 genes do not affect multiple myeloma (MM) risk. However, specific genotypes, like GSTM1 null and P53 PP+AP, may influence MM progression in Brazilian patients.

Area of Science:

  • Genetics
  • Oncology
  • Molecular Biology

Background:

  • Glutathione S-transferase (GST) enzymes, encoded by GSTM1 and GSTT1 genes, detoxify cytotoxic agents.
  • The P53 tumor suppressor gene has a common polymorphism at amino acid position 72, resulting in arginine (A) or proline (P) variants with distinct functions.
  • The association between GSTM1, GSTT1, and P53 genotypes and multiple myeloma (MM) risk remains largely unexplored.

Purpose of the Study:

  • To investigate the potential association between GSTM1, GSTT1, and P53 genotypes and the risk of developing multiple myeloma (MM) in a Brazilian population.
  • To explore if these genetic variations influence disease progression in MM patients.

Main Methods:

  • Genomic DNA was collected from 106 MM patients and 230 healthy controls.
  • Polymerase chain reaction (PCR)-based methods were employed to determine the genotypes of GSTM1, GSTT1, and P53.
  • Statistical analyses were performed to compare genotype frequencies and disease risk between patients and controls, and across different disease stages.

Main Results:

  • No significant differences in the frequencies of GSTM1, GSTT1, and P53 genotypes were observed between MM patients and controls.
  • Individuals with specific genotypes, including GSTM1 null and P53 PP+AP, showed an increased prevalence in advanced Stage III MM compared to Stages I+II.
  • The combined GSTM1 null and P53 PP+AP genotypes were significantly more frequent in Stage III MM patients.

Conclusions:

  • GSTM1, GSTT1, and P53 genotypes do not appear to be risk factors for developing multiple myeloma (MM).
  • The study identified a potential role for the variant codon 72 P53 allele and the absence of the GSTM1 detoxification pathway in the progression of MM.
  • These findings suggest that while not affecting initial risk, certain genetic profiles may influence disease advancement in the Brazilian population.

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