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The CYP1B1_1358_GG genotype is associated with estrogen receptor-negative breast cancer

  • Epidemiology
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Abstract

Cytochrome P450 1B1 (CYP1B1) is a major enzyme in the initial catabolic step of estradiol (E2) metabolism and belongs to the multitude of genes regulated by the estrogen receptor alpha (ERα). The common non-synonymous polymorphisms CYP1B1_1358_A>G and CYP1B1_1294_C>G increase CYP1B1 enzymatic activity. Given a relationship between CYP1B1 and breast tumor E2 level as well as E2 level and breast tumor ERα expression it is of interest to know whether CYP1B1 polymorphisms have an impact on the ERα status of breast cancer. We genotyped the GENICA population-based breast cancer case–control collection (1,021 cases, 1,015 controls) by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and investigated in cases the association between genotypes and tumor ERα status (739 ERα positive cases; 212 ERα negative cases) by logistic regression. We observed a significant association between the homozygous variant CYP1B1_1358_GG genotype and negative ERα status (P = 0.005; OR 2.82, 95% CI: 1.37–5.82) with a highly significant P trend for CYP1B1_1358_A>G and negative ERα status (P = 0.003). We also observed an association of CYP1B1_1358_GG and negative PR status (P = 0.015; OR 2.36, 95% CI: 1.18–4.70) and a P trend of 0.111 for CYP1B1_1358_A>G and negative progesterone receptor (PR) status. We conclude that the CYP1B1_1358_A>G polymorphism has an impact on ERα status in breast cancer in that the CYP1B1_1358_GG genotype known to encode higher CYP1B1 activity is associated with ERα negativity.

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Acknowledgements

We are indebted to all women participating in the GENICA study. We gratefully acknowledge support by interviewers as well as physicians and pathologists of the study region. High-throughput genotyping analyses were supported by Sandra Brod. This work was supported by the Federal Ministry of Education and Research (BMBF) Germany grants 01KW9975/5, 01KW9976/8, 01KW9977/0, and 01KW0114, the Robert Bosch Foundation of Medical Research, Stuttgart, Deutsches Krebsforschungszentrum, Heidelberg, Berufsgenossenschaftliches Forschungsinstitut für Arbeitsmedizin, Bochum, Department of Internal Medicine, Evangelische Kliniken Bonn gGmbH, Johanniter Krankenhaus, Bonn, Germany.

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Authors and Affiliations

  1. Molecular Mechanisms of Origin and Treatment of Breast Cancer, Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, 70376, Stuttgart, Germany

    Christina Justenhoven & Hiltrud Brauch

  2. University Tuebingen, Tuebingen, Germany

    Christina Justenhoven & Hiltrud Brauch

  3. Berufsgenossenschaftliches Forschungsinstitut für Arbeitsmedizin (BGFA), Ruhr University Bochum, Bochum, Germany

    Christiane B. Pierl, Beate Pesch & Thomas Brüning

  4. Institute of Pathology, Medical Faculty of the University of Bonn, Bonn, Germany

    Susanne Haas & Hans-Peter Fischer

  5. Department of Internal Medicine, Evangelische Kliniken Bonn gGmbH, Johanniter Krankenhaus, Bonn, Germany

    Christian Baisch, Volker Harth & Yon-Dschun Ko

  6. Molecular Genetics of Breast Cancer, Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Germany

    Ute Hamann

  7. Institute of Epidemiology, GSF-National Research Center for Environment and Health, Neuherberg, Germany

    Caren Vollmert & Thomas Illig

  8. Department of Mathematics, Universität Stuttgart, Stuttgart, Germany

    Jürgen Dippon

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  1. Christina Justenhoven
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  2. Christiane B. Pierl
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  3. Susanne Haas
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  4. Hans-Peter Fischer
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  6. Ute Hamann
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  7. Volker Harth
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  8. Beate Pesch
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  10. Caren Vollmert
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  11. Thomas Illig
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  14. Hiltrud Brauch
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Correspondence to Hiltrud Brauch.

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Justenhoven, C., Pierl, C.B., Haas, S. et al. The CYP1B1_1358_GG genotype is associated with estrogen receptor-negative breast cancer. Breast Cancer Res Treat 111, 171–177 (2008). https://doi.org/10.1007/s10549-007-9762-x

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  • DOI: https://doi.org/10.1007/s10549-007-9762-x

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