CYP2C19*2 and CYP2C19*17 variants and effect of tamoxifen on breast cancer recurrence: Analysis of the International Tamoxifen Pharmacogenomics Consortium dataset
Abstract The role of cytochrome P450 drug metabolizing enzymes in the efficacy of tamoxifen treatment of breast cancer is subject to substantial interest and controversy. CYP2D6 have been intensively studied, but the role of CYP2C19 is less elucidated, and we studied the association of CYPC19 genoty...
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Nature Portfolio
2017
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oai:doaj.org-article:4ceb888b86f14d59982b5e5a3175cd152021-12-02T11:52:57ZCYP2C19*2 and CYP2C19*17 variants and effect of tamoxifen on breast cancer recurrence: Analysis of the International Tamoxifen Pharmacogenomics Consortium dataset10.1038/s41598-017-08091-x2045-2322https://doaj.org/article/4ceb888b86f14d59982b5e5a3175cd152017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-08091-xhttps://doaj.org/toc/2045-2322Abstract The role of cytochrome P450 drug metabolizing enzymes in the efficacy of tamoxifen treatment of breast cancer is subject to substantial interest and controversy. CYP2D6 have been intensively studied, but the role of CYP2C19 is less elucidated, and we studied the association of CYPC19 genotype and recurrence of breast cancer. We used outcome and genotyping data from the large publicly available International Tamoxifen Pharmacogenomics Consortium (ITPC) dataset. Cox regression was used to compute the hazard ratios (HRs) for recurrence. CYP2C19 genotype data was available for 2 423 patients and the final sample cohort comprised 2 102 patients. CYP2C19*2 or *19 alleles did not influence DFS. For the CYP2C19*2 allele, the HR was 1.05 (CI 0.78–1.42) and 0.79 (CI 0.32–1.94) for hetero- and homozygote carriers, respectively. The corresponding HR for hetero- and homozygote carriers of the CYP2C19*17 allele were 1.02 (CI 0.71–1.46) and 0.57 (CI 0.26–1.24), respectively. Accounting for CYP2D6 genotype status did not change these estimates. We found no evidence to support a clinically meaningful role of CYP2C19 polymorphisms and response to tamoxifen in breast cancer patients and, consequently, CYP2C19 genotype status should not be included in clinical decisions on tamoxifen treatment.Per DamkierAnders KjærsgaardKimberly A. BarkerDeidre Cronin-FentonAnatasha CrawfordYlva HellbergEmilius A. M. JanssenCarl LangefeldThomas P. AhernTimothy L. LashNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-8 (2017) |
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Medicine R Science Q |
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Medicine R Science Q Per Damkier Anders Kjærsgaard Kimberly A. Barker Deidre Cronin-Fenton Anatasha Crawford Ylva Hellberg Emilius A. M. Janssen Carl Langefeld Thomas P. Ahern Timothy L. Lash CYP2C19*2 and CYP2C19*17 variants and effect of tamoxifen on breast cancer recurrence: Analysis of the International Tamoxifen Pharmacogenomics Consortium dataset |
| description |
Abstract The role of cytochrome P450 drug metabolizing enzymes in the efficacy of tamoxifen treatment of breast cancer is subject to substantial interest and controversy. CYP2D6 have been intensively studied, but the role of CYP2C19 is less elucidated, and we studied the association of CYPC19 genotype and recurrence of breast cancer. We used outcome and genotyping data from the large publicly available International Tamoxifen Pharmacogenomics Consortium (ITPC) dataset. Cox regression was used to compute the hazard ratios (HRs) for recurrence. CYP2C19 genotype data was available for 2 423 patients and the final sample cohort comprised 2 102 patients. CYP2C19*2 or *19 alleles did not influence DFS. For the CYP2C19*2 allele, the HR was 1.05 (CI 0.78–1.42) and 0.79 (CI 0.32–1.94) for hetero- and homozygote carriers, respectively. The corresponding HR for hetero- and homozygote carriers of the CYP2C19*17 allele were 1.02 (CI 0.71–1.46) and 0.57 (CI 0.26–1.24), respectively. Accounting for CYP2D6 genotype status did not change these estimates. We found no evidence to support a clinically meaningful role of CYP2C19 polymorphisms and response to tamoxifen in breast cancer patients and, consequently, CYP2C19 genotype status should not be included in clinical decisions on tamoxifen treatment. |
| format |
article |
| author |
Per Damkier Anders Kjærsgaard Kimberly A. Barker Deidre Cronin-Fenton Anatasha Crawford Ylva Hellberg Emilius A. M. Janssen Carl Langefeld Thomas P. Ahern Timothy L. Lash |
| author_facet |
Per Damkier Anders Kjærsgaard Kimberly A. Barker Deidre Cronin-Fenton Anatasha Crawford Ylva Hellberg Emilius A. M. Janssen Carl Langefeld Thomas P. Ahern Timothy L. Lash |
| author_sort |
Per Damkier |
| title |
CYP2C19*2 and CYP2C19*17 variants and effect of tamoxifen on breast cancer recurrence: Analysis of the International Tamoxifen Pharmacogenomics Consortium dataset |
| title_short |
CYP2C19*2 and CYP2C19*17 variants and effect of tamoxifen on breast cancer recurrence: Analysis of the International Tamoxifen Pharmacogenomics Consortium dataset |
| title_full |
CYP2C19*2 and CYP2C19*17 variants and effect of tamoxifen on breast cancer recurrence: Analysis of the International Tamoxifen Pharmacogenomics Consortium dataset |
| title_fullStr |
CYP2C19*2 and CYP2C19*17 variants and effect of tamoxifen on breast cancer recurrence: Analysis of the International Tamoxifen Pharmacogenomics Consortium dataset |
| title_full_unstemmed |
CYP2C19*2 and CYP2C19*17 variants and effect of tamoxifen on breast cancer recurrence: Analysis of the International Tamoxifen Pharmacogenomics Consortium dataset |
| title_sort |
cyp2c19*2 and cyp2c19*17 variants and effect of tamoxifen on breast cancer recurrence: analysis of the international tamoxifen pharmacogenomics consortium dataset |
| publisher |
Nature Portfolio |
| publishDate |
2017 |
| url |
https://doaj.org/article/4ceb888b86f14d59982b5e5a3175cd15 |
| work_keys_str_mv |
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1718394920688943104 |