Efficacy of tamoxifen based on cytochrome P450 2D6, CYP2C19 and SULT1A1 genotype in the Italian Tamoxifen Prevention Trial

D. Serrano, M. Lazzeroni, C. F. Zambon, D. MacIs, P. Maisonneuve, H. Johansson, A. Guerrieri-Gonzaga, M. Plebani, D. Basso, J. Gjerde, G. Mellgren, N. Rotmensz, A. Decensi, B. Bonanni

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Abstract

The role of pharmacogenomics and tamoxifen was investigated by analyzing several polymorphisms of cytochrome P450 and SULT1A1 gene in a nested case control study from the Italian Tamoxifen Prevention Trial. This study included 182 Caucasian subjects, 47 breast cancer (BC) cases and 135 matched controls. We used the AmpliChip CYP450 Test to screen 33 alleles of CYP2D6 and 3 of CYP2C19. One more variant for CYP2C19*17 and two single-nucleotide polymorphisms for the gene SULT1A1 were also performed. By using the AmpliChip CYP450 Test, out of 182 subjects, we identified 8 poor metabolizer (PM), 17 intermediate metabolizer (IM), 151 extensive metabolizer (EM) and 3 ultrarapid metabolizer (UM). PM women allocated to the tamoxifen arm showed a higher risk of developing BC compared to the remaining phenotypes (P=0.035). In an exploratory analysis, among 58 women with a CYP2D6*2A allele, 9 BCs were diagnosed in the placebo arm and only 1 in the tamoxifen arm (P=0.0001). CYP2C19 and SULT1A1 polymorphisms did not show any correlation with tamoxifen efficacy. Tamoxifen showed reduced efficacy in CYP2D6 PMs in the chemoprevention setting. Conversely, the CYP2D6*2A allele may be associated with increased efficacy of tamoxifen. These findings support the relevance of pharmaco-genomics in tailoring tamoxifen treatment.

Original languageEnglish
Pages (from-to)100-107
Number of pages8
JournalPharmacogenomics Journal
Volume11
Issue number2
DOIs
Publication statusPublished - Apr 2011

Fingerprint

Cytochrome P-450 CYP2D6
Tamoxifen
Genotype
Alleles
Breast Neoplasms
Cytochrome P-450 CYP2C19
Pharmacogenetics
Chemoprevention
Genomics
Cytochrome P-450 Enzyme System
Genes
Single Nucleotide Polymorphism
Case-Control Studies
Placebos
Phenotype

Keywords

  • breast cancer
  • chemoprevention
  • CYP2D6
  • genotype
  • tamoxifen

ASJC Scopus subject areas

  • Pharmacology
  • Molecular Medicine
  • Genetics

Cite this

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title = "Efficacy of tamoxifen based on cytochrome P450 2D6, CYP2C19 and SULT1A1 genotype in the Italian Tamoxifen Prevention Trial",
abstract = "The role of pharmacogenomics and tamoxifen was investigated by analyzing several polymorphisms of cytochrome P450 and SULT1A1 gene in a nested case control study from the Italian Tamoxifen Prevention Trial. This study included 182 Caucasian subjects, 47 breast cancer (BC) cases and 135 matched controls. We used the AmpliChip CYP450 Test to screen 33 alleles of CYP2D6 and 3 of CYP2C19. One more variant for CYP2C19*17 and two single-nucleotide polymorphisms for the gene SULT1A1 were also performed. By using the AmpliChip CYP450 Test, out of 182 subjects, we identified 8 poor metabolizer (PM), 17 intermediate metabolizer (IM), 151 extensive metabolizer (EM) and 3 ultrarapid metabolizer (UM). PM women allocated to the tamoxifen arm showed a higher risk of developing BC compared to the remaining phenotypes (P=0.035). In an exploratory analysis, among 58 women with a CYP2D6*2A allele, 9 BCs were diagnosed in the placebo arm and only 1 in the tamoxifen arm (P=0.0001). CYP2C19 and SULT1A1 polymorphisms did not show any correlation with tamoxifen efficacy. Tamoxifen showed reduced efficacy in CYP2D6 PMs in the chemoprevention setting. Conversely, the CYP2D6*2A allele may be associated with increased efficacy of tamoxifen. These findings support the relevance of pharmaco-genomics in tailoring tamoxifen treatment.",
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AU - Lazzeroni, M.

AU - Zambon, C. F.

AU - MacIs, D.

AU - Maisonneuve, P.

AU - Johansson, H.

AU - Guerrieri-Gonzaga, A.

AU - Plebani, M.

AU - Basso, D.

AU - Gjerde, J.

AU - Mellgren, G.

AU - Rotmensz, N.

AU - Decensi, A.

AU - Bonanni, B.

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