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Breast Cancer Research and Treatment

, Volume 125, Issue 2, pp 563–569 | Cite as

Polymorphisms of the nuclear receptor pregnane X receptor and organic anion transporter polypeptides 1A2, 1B1, 1B3, and 2B1 are not associated with breast cancer risk

  • Christina Justenhoven
  • Elke Schaeffeler
  • Stefan Winter
  • Christian Baisch
  • Ute Hamann
  • Volker Harth
  • Sylvia Rabstein
  • Anne Spickenheuer
  • Beate Pesch
  • Thomas Brüning
  • Yon-Dschun Ko
  • Matthias Schwab
  • Hiltrud Brauch
Epidemiology

Abstract

Organic anion transporter polypeptides (OATPs, SLCOs) are involved in the uptake of conjugates steroid hormones such as estrone-3-sulfate. It has been suggested that the expression of OATPs in breast tissues could impact breast carcinogenesis and tumor pathology. The nuclear receptor pregnane X receptor (PXR) is involved in the regulation of SLCO1A2 expression. We investigated 31 variants located in PXR, SLCO1A2, SLCO1B1, SLCO1B3, and SLCO2B1 for an association with breast cancer risk and/or histo-pathological tumor characteristics. Polymorphisms were selected on the basis of a known or potential functional consequence and an allele frequency >2%. Genotyping was performed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry using the GENICA population-based breast cancer case–control collection comprising 1,021 cases and 1,015 age-matched controls. Statistical analysis was performed by SAS, and all tests were two-sided. None of the 31 analyzed transporter and PXR polymorphisms showed an association with breast cancer risk or tumor characteristics. Our data suggest that among the many known transporters common variations of PXR, SLCO1A2, SLCO1B1, SLCO1B3, and SLCO2B1 do not contribute to breast carcinogenesis.

Keywords

PXR OATP SLCO Polymorphisms Breast cancer risk 

Notes

Acknowledgments

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. This study was supported by the Federal Ministry of Education and Research (BMBF) Germany grants 01KW9975/5, 01KW9976/8, 01KW9977/0, 01KW0114, 03IS2061C, and 012P0502, as well as the Robert Bosch Foundation, Stuttgart; Department of Internal Medicine, Evangelische Kliniken Bonn gGmbH, Johanniter Krankenhaus, Bonn; Institute of Pathology, Medical Faculty of the University of Bonn, Deutsches Krebsforschungszentrum, Heidelberg; and Institute for Prevention and Occupational Medicine of the German Social Accident Insurance (IPA), Bochum, Germany.

Conflict of interest statement

None.

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Copyright information

© Springer Science+Business Media, LLC. 2010

Authors and Affiliations

  • Christina Justenhoven
    • 1
    • 2
  • Elke Schaeffeler
    • 1
    • 2
  • Stefan Winter
    • 1
    • 2
  • Christian Baisch
    • 3
  • Ute Hamann
    • 4
  • Volker Harth
    • 5
  • Sylvia Rabstein
    • 5
  • Anne Spickenheuer
    • 5
  • Beate Pesch
    • 5
  • Thomas Brüning
    • 5
  • Yon-Dschun Ko
    • 3
  • Matthias Schwab
    • 1
    • 2
    • 6
  • Hiltrud Brauch
    • 1
    • 2
  1. 1.Dr. Margarete Fischer-Bosch-Institute of Clinical PharmacologyStuttgartGermany
  2. 2.University of TübingenTübingenGermany
  3. 3.Department of Internal MedicineEvangelische Kliniken Bonn gGmbH, Johanniter KrankenhausBonnGermany
  4. 4.Molecular Genetics of Breast Cancer, Deutsches Krebsforschungszentrum (DKFZ)HeidelbergGermany
  5. 5.Institute for Prevention and Occupational Medicine of the German Social Accident Insurance (IPA)BochumGermany
  6. 6.Department of Clinical Pharmacology, Institute of Experimental and Clinical Pharmacology and ToxicologyUniversity HospitalTübingenGermany

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