ArticleBreast cancer research and treatment2017
SLCO1B1 polymorphisms and plasma estrone conjugates in postmenopausal women with ER+ breast cancer: genome-wide association studies of the estrone pathway.
Article in Breast cancer research and treatment, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 22 citations in OpenAlex.
- Effects ofPharmacogenomics · 2019Trial
- Genetic Variation in Steroid and Xenobiotic Metabolizing Pathways and Enterolactone Excretion Before and After Flaxseed Intervention in African American and European American Women.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2019Trial
- SLCO1B1 genetic variation and hormone therapy in menopausal women.Menopause (New York, N.Y.) · 2018Trial
- Genome-wide association studies of missing metabolite measures from two population-based studies.Genome biology · 2026Article
- Determination and Disposition of the Aromatase Inhibitor Exemestane in CYP3A-Deficient Mice.Molecules (Basel, Switzerland) · 2025Article
- Genetic Variations in CYP19A1 and SLCO1B1 Genes and Their Association with Endometrial Cancer Risk in the Taiwanese Population: A Case-Control Study.International journal of molecular sciences · 2025Article
- OATP1B-type Transport Function Is a Determinant of Aromatase Inhibitor-Associated Arthralgia Susceptibility.Cancer research communications · 2025Article
- Effect of Genetic Variations in Drug-Metabolizing Enzymes and Drug Transporters on the Pharmacokinetics of Rifamycins: A Systematic Review.Pharmacogenomics and personalized medicine · 2022Review
- Article
- Genetic Influences in Breast Cancer Drug Resistance.Breast cancer (Dove Medical Press) · 2021Review
- Organic Anion Transporting Polypeptide 2B1 (OATP2B1) Genetic Variants:Frontiers in pharmacology · 2021Article
- Influence of Single Nucleotide Polymorphisms on Rifampin Pharmacokinetics in Tuberculosis Patients.Antibiotics (Basel, Switzerland) · 2020Review
- Unraveling the functional role of the orphan solute carrier, SLC22A24 in the transport of steroid conjugates through metabolomic and genome-wide association studies.PLoS genetics · 2019Article
- Single Nucleotide Polymorphisms at a Distance from Aryl Hydrocarbon Receptor (AHR) Binding Sites Influence AHR Ligand-Dependent Gene Expression.Drug metabolism and disposition: the biological fate of chemicals · 2019Article
- Organic Anion Transporting Polypeptides: Emerging Roles in Cancer Pharmacology.Molecular pharmacology · 2019Review
- In Vitro and In Vivo Anti-Breast Cancer Activities of Some Synthesized Pyrazolinyl-estran-17-one Candidates.Molecules (Basel, Switzerland) · 2018Article
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Authors and funding
19 authors at 8 institutions in 2 countries.
Funding
Abstract
backgroundEstrone (E1), the major circulating estrogen in postmenopausal women, promotes estrogen-receptor positive (ER+) breast tumor growth and proliferation. Two major reactions contribute to E1 plasma concentrations, aromatase (CYP19A1) catalyzed E1 synthesis from androstenedione and steroid sulfatase (STS) catalyzed hydrolysis of estrone conjugates (E1Cs). E1Cs have been associated with breast cancer risk and may contribute to tumor progression since STS is expressed in breast cancer where its activity exceeds that of aromatase.
methodsWe performed genome-wide association studies (GWAS) to identify SNPs associated with variation in plasma concentrations of E1Cs, E1, and androstenedione in 774 postmenopausal women with resected early-stage ER+ breast cancer. Hormone concentrations were measured prior to aromatase inhibitor therapy.
resultsMultiple SNPs in SLCO1B1, a gene encoding a hepatic influx transporter, displayed genome-wide significant associations with E1C plasma concentrations and with the E1C/E1 ratio. The top SNP for E1C concentrations, rs4149056 (p = 3.74E-11), was a missense variant that results in reduced transporter activity. Patients homozygous for the variant allele had significantly higher average E1C plasma concentrations than did other patients. Furthermore, three other SLCO1B1 SNPs, not in LD with rs4149056, were associated with both E1C concentrations and the E1C/E1 ratio and were cis-eQTLs for SLCO1B3. GWAS signals of suggestive significance were also observed for E1, androstenedione, and the E1/androstenedione ratio.
conclusionThese results suggest a mechanism for genetic variation in E1C plasma concentrations as well as possible SNP biomarkers to identify ER+ breast cancer patients for whom STS inhibitors might be of clinical value.
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