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The CYP2D6*4 polymorphism affects breast cancer survival in tamoxifen users

  • Epidemiology
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Abstract

Cytochrome P450 2D6 (CYP2D6) plays an important role in the formation of endoxifen, the active metabolite of tamoxifen. In this study the association between the most prevalent CYP2D6 null-allele in Caucasians (CYP2D6*4) and breast cancer mortality was examined among all incident users of tamoxifen in a population-based cohort study. Breast cancer mortality was significantly increased in patients with the * 4/*4 genotype (HR = 4.1, CI 95% 1.1–15.9, P = 0.041) compared to wild type patients. The breast cancer mortality increased with a hazard ratio of 2.0 (CI 95% 1.1–3.4, P = 0.015) with each additional variant allele. No increased risk of all-cause mortality or all-cancer mortality was found in tamoxifen users carrying a CYP2D6*4 allele. The risk of breast cancer mortality is increased in tamoxifen users with decreased CYP2D6 activity, consistent with the model in which endoxifen formation is dependent on CYP2D6 activity.

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Acknowledgments

This work is supported by the Netherlands Genomics Initiative (NGI)/Netherlands Organisation for Scientific Research (NWO) [050.060.810]. The Rotterdam Study is supported by the Erasmus Medical Center and Erasmus University Rotterdam; the Netherlands Organization for Scientific Research; the Netherlands Organization for Health Research and Development (ZonMw); the Research Institute for Diseases in the Elderly; the Ministry of Education, Culture and Science; the Ministry of Health Welfare and Sports; the European Commission; and the Municipality of Rotterdam.

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Authors and Affiliations

  1. Department of Epidemiology, Erasmus MC, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands

    Monique J. Bijl, Albert Hofman, Bruno H. Ch. Stricker & Loes E. Visser

  2. Department of Hospital Pharmacy, Erasmus MC, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands

    Monique J. Bijl, Laureen A. Lammers, Arnold G. Vulto, Teun van Gelder & Loes E. Visser

  3. Department of Clinical Chemistry, Erasmus MC, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands

    Ron H. N. van Schaik

  4. Department of Internal Medicine, Erasmus MC, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands

    Teun van Gelder & Bruno H. Ch. Stricker

  5. Drug Safety Unit, Inspectorate for Health Care, P.O. Box 16119, 2500 BC, The Hague, The Netherlands

    Bruno H. Ch. Stricker

Authors
  1. Monique J. Bijl
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  2. Ron H. N. van Schaik
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  3. Laureen A. Lammers
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  4. Albert Hofman
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  8. Loes E. Visser
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Corresponding author

Correspondence to Bruno H. Ch. Stricker.

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Bijl, M.J., van Schaik, R.H.N., Lammers, L.A. et al. The CYP2D6*4 polymorphism affects breast cancer survival in tamoxifen users. Breast Cancer Res Treat 118, 125–130 (2009). https://doi.org/10.1007/s10549-008-0272-2

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  • DOI: https://doi.org/10.1007/s10549-008-0272-2

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