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 (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 Dr. Margarete Fischer-Bosch Institute for Clinical Pharmacology [Stuttgart]
2 Eberhard Karls Universität Tübingen = Eberhard Karls University of Tuebingen
3 Department of Internal Medicine
4 Molecular Genetics of Breast Cancer, Deutsches Krebsforschungszentrum (DKFZ)
5 IPA - Institute for Prevention and Occupational Medicine of the German Social Accident Insurance
6 Department of Clinical Pharmacology, Institute of Experimental and Clinical Pharmacology and Toxicology

Organic anion transporter polypeptides (OATPs, s) 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 expression. We investigated 31 variants located in , , , , and 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 , , , , and do not contribute to breast carcinogenesis.

Mots clés: PXR; OATP; SLCO; Polymorphisms; Breast cancer risk

Christina Justenhoven, Elke Schaeffeler, Stefan Winter, Christian Baisch, Ute Hamann, et al.. 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. Breast Cancer Research and Treatment, 2010, 125 (2), pp.563-569. ⟨10.1007/s10549-010-1046-1⟩. ⟨hal-00556268⟩