title: 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.
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.
authors.affiliation: Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Justenhoven
authors.forename: Elke
authors.initials: E
authors.lastname: Schaeffeler
authors.forename: Stefan
authors.initials: S
authors.lastname: Winter
authors.forename: Christian
authors.initials: C
authors.lastname: Baisch
authors.forename: Ute
authors.initials: U
authors.lastname: Hamann
authors.forename: Volker
authors.initials: V
authors.lastname: Harth
authors.forename: Sylvia
authors.initials: S
authors.lastname: Rabstein
authors.forename: Anne
authors.initials: A
authors.lastname: Spickenheuer
authors.forename: Beate
authors.initials: B
authors.lastname: Pesch
authors.forename: Thomas
authors.initials: T
authors.lastname: Brüning
authors.forename: Yon-Dschun
authors.initials: YD
authors.lastname: Ko
authors.forename: Matthias
authors.initials: M
authors.lastname: Schwab
authors.forename: Hiltrud
authors.initials: H
authors.lastname: Brauch
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D027381:Liver-Specific Organic Anion Transporter 1; D027361:Organic Anion Transporters / Q000235:genetics*; D029362:Organic Anion Transporters, Sodium-Independent / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D000077297:Pregnane X Receptor; D011987:Receptors, Steroid / Q000235:genetics*; D012306:Risk; D000074542:Solute Carrier Organic Anion Transporter Family Member 1B3
chemical_list: D027381:Liver-Specific Organic Anion Transporter 1; D027361:Organic Anion Transporters; D029362:Organic Anion Transporters, Sodium-Independent; D000077297:Pregnane X Receptor; D011987:Receptors, Steroid; C512988:SLCO1A2 protein, human; C503999:SLCO1B1 protein, human; C421209:SLCO1B3 protein, human; C450859:SLCO2B1 protein, human; D000074542:Solute Carrier Organic Anion Transporter Family Member 1B3