SNPs and taxane toxicity in breast cancer patients

Autores de IIS La Fe

• Virginia Bosó Ribelles

  Autor

• María José Herrero Cervera

  Autor

• Ana Santaballa Bertrán

  Autor

• Laura Palomar Abad

  Autor

• Juan Eduardo Megías Vericat

  Autor

• Luis Esteban Rojas Orellana

  Autor

• María Remedios Marques Miñana

  Autor

• José Luis Poveda Andrés

  Autor

• Joaquin Montalar Salcedo

  Autor

• Salvador F Aliño Pellicer

  Autor

Participantes ajenos a IIS La Fe

• de la Cueva H

Grupos

• Farmacogenética

• Investigación Clínica y Traslacional en Cáncer

Abstract

Aim: In order to identify genetic variants associated with taxanes toxicity, a panel with 47 SNPs in 20 genes involved in taxane pathways was designed. Patients & methods: Genomic DNA of 113 breast cancer patients was analyzed (70 taking docetaxel, 43 taking paclitaxel). Results: Two SNPs associated with docetaxel toxicity were identified: CYP3A4*1B with infusion-related reactions; and ERCC1 Gln504Lys with mucositis (p <= 0.01). Regarding paclitaxel toxicity: CYP2C8 HapC and CYP2C8 rs1934951 were associated with anemia; and ERCC1 Gln504Lys with neuropathy (p <= 0.01). Conclusion: Genes involved in DNA repair mechanisms and reactive oxygen species levels influence taxane toxicity in cancer patients treated with chemotherapy schemes not containing platinum. These findings could lead to better treatment selection for breast cancer patients.

Keywords

• breast neoplasms; drug-related adverse reactions; genetic polymorphism; pharmacogenetics; taxoids