Comparative Study of Polymorphism Frequencies of the CYP2D6, CYP3A5, CYP2C8 and IL-10 Genes in Mexican and Spanish Women with Breast Cancer

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.

Original submitted 1 February 2013; revision submitted 22 April 2013

KEYWORDS::

• breast cancer
• capecitabine
• DNA
• paclitaxel
• pharmacogenetics
• polymorphism
• tamoxifen

Acknowledgements

The authors gratefully acknowledge the critical reading of the manuscript by S Lozano. The authors thank the patients for their valuable participation in this study and the authorities of the Hospital Universitario and the IMSS Hospital 25 for their cooperation.

Financial & competing interests disclosure

This work was supported by grants from the Ministry of Public Education of Mexico through the program PROMEP UANL-PTC-487 (to ML Garza-Rodríguez) and from the Council of Science and Technology (CONACYT), FONCICYT-95773 (to HA Barrera-Saldaña). The authors affiliated to Progenika Biopharma, S.A. have potential financial interest in the medical device tested in this paper. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Additional information

Funding

This work was supported by grants from the Ministry of Public Education of Mexico through the program PROMEP UANL-PTC-487 (to ML Garza-Rodríguez) and from the Council of Science and Technology (CONACYT), FONCICYT-95773 (to HA Barrera-Saldaña). The authors affiliated to Progenika Biopharma, S.A. have potential financial interest in the medical device tested in this paper. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.