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GSTP1 and MTHFR polymorphisms are related with toxicity in breast cancer adjuvant anthracycline-based treatment

R Zárate1, S González-Santigo, J de la Haba

  • 1Laboratory of Biotechnology, University Clinic of Navarra, Pamplona, Spain. rzarate@unav.es

Current Drug Metabolism
|June 23, 2007
PubMed

Insights

Genetic variations in GSTP1 and MTHFR influence drug toxicity in breast cancer patients receiving anthracycline chemotherapy. These gene polymorphisms are key predictors of adverse events, aiding personalized treatment strategies.

Area of Science:

  • Pharmacogenomics
  • Oncology
  • Molecular Biology

Background:

  • Adjuvant anthracycline-based chemotherapy is standard for breast cancer.
  • Drug bioavailability and toxicity can vary significantly due to genetic factors.
  • Identifying genetic predictors of toxicity is crucial for optimizing patient outcomes.

Purpose of the Study:

  • To investigate the association between genetic polymorphisms in drug-metabolizing enzymes (DMEs) and tumor aggressivity genes.
  • To determine if specific genetic variations predict systemic drug bioavailability and toxicity in breast cancer patients undergoing anthracycline treatment.

Main Methods:

  • Analysis of fourteen previously identified polymorphisms in 94 breast cancer patients.
  • Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) and sequencing techniques were employed.
  • Multivariate logistic regression analysis was used to identify significant predictors.

Main Results:

  • GSTP1A>G and MTHFR 1298A>C genotypes were significant predictors of toxicity.
  • GSTP1 polymorphism correlated with hematological toxicity (P = 0.044, HR= 6.4).
  • MTHFR-1298 AC+CC genotypes were associated with increased non-hematological toxicity (P = 0.008, HR = 24).

Conclusions:

  • GSTP1 and MTHFR genotypes are relevant and independent factors influencing toxicity in adjuvant anthracycline-based breast cancer treatment.
  • These findings support the potential for using genetic profiling to personalize chemotherapy regimens.
  • Further research can validate these genetic markers for clinical application in breast cancer management.

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