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SNPs and taxane toxicity in breast cancer patients

Virginia Bosó1, María José Herrero, Ana Santaballa

  • 1Pharmacogenetics Unit, Pharmacy Department, Hospital Universitari i Politècnic La Fe, Valencia, Spain.

Pharmacogenomics
|December 16, 2014
PubMed
Abstract

Insights

Genetic variants in CYP3A4, ERCC1, and CYP2C8 influence taxane chemotherapy side effects in breast cancer patients. Identifying these genetic markers can help personalize treatment and reduce toxicity.

Area of Science:

  • Pharmacogenomics
  • Oncology
  • Molecular Biology

Background:

  • Taxanes are widely used chemotherapy agents for breast cancer.
  • Chemotherapy-induced toxicity can significantly impact patient outcomes and treatment adherence.
  • Genetic factors are increasingly recognized as contributors to inter-individual variability in drug response and toxicity.

Purpose of the Study:

  • To identify single nucleotide polymorphisms (SNPs) associated with taxane-induced toxicity in breast cancer patients.
  • To investigate the role of genes involved in taxane metabolism and DNA repair in predicting toxicity.
  • To explore potential genetic markers for personalized taxane therapy selection.

Main Methods:

  • A panel of 47 SNPs in 20 genes related to taxane pathways was designed.
  • Genomic DNA from 113 breast cancer patients (70 on docetaxel, 43 on paclitaxel) was analyzed.
  • Statistical analysis was performed to correlate SNP genotypes with specific toxicities.

Main Results:

  • Two SNPs (CYP3A4*1B and ERCC1 Gln504Lys) were associated with docetaxel toxicity (infusion-related reactions and mucositis, respectively).
  • For paclitaxel toxicity, CYP2C8 HapC, CYP2C8 rs1934951, and ERCC1 Gln504Lys were linked to anemia and neuropathy.
  • Significant associations were observed with p-values less than or equal to 0.01.

Conclusions:

  • Genes involved in DNA repair and reactive oxygen species pathways influence taxane toxicity in patients receiving platinum-free chemotherapy.
  • The identified genetic variants may serve as predictive biomarkers for taxane-induced adverse events.
  • These findings support the potential for genetic profiling to optimize breast cancer treatment selection and improve patient safety.
Keywords:
breast neoplasmsdrug-related adverse reactionsgenetic polymorphismpharmacogeneticstaxoids

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