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

The Pharmacogenomics Journal volume 11, pages 100–107 (2011)Cite this article

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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.

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Acknowledgements

This study was supported by grants from the Italian National Research Council, the Italian Association for Cancer Research, the American-Italian Cancer Foundation, the Italian League Against Cancer and the Grieg Foundation. We gratefully acknowledge the contributions of Marcel Fontecha, Lothar Weiczorek.

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Authors and Affiliations

  1. Division of Cancer Prevention and Genetics, European Institute of Oncology, Milan, Italy

    D Serrano, M Lazzeroni, D Macis, H Johansson, A Guerrieri-Gonzaga, A Decensi & B Bonanni

  2. University of Rome Tor Vergata, School of Oncology, Rome, Italy

    M Lazzeroni

  3. Department of Laboratory Medicine, University-Hospital of Padova, Padova, Italy

    C-F Zambon, M Plebani & D Basso

  4. Division of Epidemiology and Biostatistics, European Institute of Oncology, Milan, Italy

    P Maisonneuve & N Rotmensz

  5. Hormone Laboratory, Haukeland University Hospital, Bergen, Norway

    J Gjerde & G Mellgren

  6. Institute of Medicine, University of Bergen, Bergen, Norway

    G Mellgren

  7. Division of Medical Oncology, E.O. Ospedali Galliera, Genova, Italy

    A Decensi

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  1. D Serrano
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Correspondence to D Serrano.

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Serrano, D., Lazzeroni, M., Zambon, CF. et al. Efficacy of tamoxifen based on cytochrome P450 2D6, CYP2C19 and SULT1A1 genotype in the Italian Tamoxifen Prevention Trial. Pharmacogenomics J 11, 100–107 (2011). https://doi.org/10.1038/tpj.2010.17

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  • DOI: https://doi.org/10.1038/tpj.2010.17

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