Comparative study of polymorphism frequencies of the CYP2D6, CYP3A5, CYP2C8 and IL-10 genes in Mexican and Spanish women with breast cancer

Pharmacogenomics. 2013 Oct;14(13):1583-92. doi: 10.2217/pgs.13.83.

Abstract

Aim: Pharmacogenetic studies in breast cancer (BC) may predict the efficacy of tamoxifen and the toxicity of paclitaxel and capecitabine. We determined the frequency of polymorphisms in the CYP2D6 gene associated with activation of tamoxifen, and those of the genes CYP2C8, CYP3A5 and DPYD associated with toxicity of paclitaxel and capecitabine. We also included a IL-10 gene polymorphism associated with advanced tumor stage at diagnosis.

Patients & methods: Genomic DNAs from 241 BC patients from northeast Mexico were genotyped using DNA microarray technology.

Results: For tamoxifen processing, CYP2D6 genotyping predicted that 90.8% of patients were normal metabolizers, 4.2% ultrarapid, 2.1% intermediate and 2.9% poor metabolizers. For paclitaxel and the CYP2C8 gene, 75.3% were normal, 23.4% intermediate and 1.3% poor metabolizers. Regarding the DPYD gene, only one patient was a poor metabolizer. For the IL-10 gene, 47.1% were poor metabolizers.

Conclusion: These results contribute valuable information towards personalizing BC chemotherapy in Mexican women.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antimetabolites, Antineoplastic / therapeutic use
  • Antineoplastic Agents, Hormonal / therapeutic use
  • Antineoplastic Agents, Phytogenic / therapeutic use
  • Aryl Hydrocarbon Hydroxylases / genetics*
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / genetics*
  • Capecitabine
  • Cytochrome P-450 CYP2C8
  • Cytochrome P-450 CYP2D6 / genetics*
  • Cytochrome P-450 CYP3A / genetics*
  • Deoxycytidine / analogs & derivatives
  • Deoxycytidine / therapeutic use
  • Female
  • Fluorouracil / analogs & derivatives
  • Fluorouracil / therapeutic use
  • Genotype
  • Humans
  • Interleukin-10 / genetics*
  • Mexico
  • Middle Aged
  • Paclitaxel / therapeutic use
  • Polymorphism, Genetic / genetics*
  • Spain
  • Tamoxifen / therapeutic use

Substances

  • Antimetabolites, Antineoplastic
  • Antineoplastic Agents, Hormonal
  • Antineoplastic Agents, Phytogenic
  • IL10 protein, human
  • Tamoxifen
  • Deoxycytidine
  • Interleukin-10
  • Capecitabine
  • Aryl Hydrocarbon Hydroxylases
  • CYP2C8 protein, human
  • CYP3A5 protein, human
  • Cytochrome P-450 CYP2C8
  • Cytochrome P-450 CYP2D6
  • Cytochrome P-450 CYP3A
  • Paclitaxel
  • Fluorouracil