SLCO2B1 and SLCO1B3 May Determine Time to Progression for Patients Receiving Androgen Deprivation Therapy for Prostate Cancer
Open accessAbstract
PURPOSE: Androgen deprivation therapy (ADT), an important treatment for advanced prostate cancer, is highly variable in its effectiveness. We hypothesized that genetic variants of androgen transporter genes, SLCO2B1 and SLCO1B3, may determine time to progression on ADT. PATIENTS AND METHODS: A cohort of 538 patients with prostate cancer treated with ADT was genotyped for SLCO2B1 and SLCO1B3 single nucleotide polymorphisms (SNP). The biologic function of a SLCO2B1 coding SNP in transporting androgen was examined through biochemical assays. RESULTS: Three SNPs in SLCO2B1 were associated with time to progression (TTP) on ADT (P < .05). The differences in median TTP for each of these polymorphisms were about 10 months. The SLCO2B1 genotype, which allows more efficient import of androgen, enhances cell growth and is associated with a shorter TTP on ADT. Patients carrying both SLCO2B1 and SLCO1B3 genotypes, which import androgens more efficiently, exhibited a median 2-year shorter TTP on ADT, demonstrating a gene-gene interaction (P(interaction) = .041). CONCLUSION: Genetic variants of SLCO2B1 and SLCO1B3 may function as pharmacogenomic determinants of resistance to ADT in prostate cancer.
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OATP polymorphisms are associated with time to progression during androgen deprivation therapy.
“and OATP polymorphisms are associated with time to progression during androgen deprivation therapy (Yang et al., 2011).”
From Intracrine androgen biosynthesis, metabolism and action revisited (2018) · cites this paper as Yang et al., 2011
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References 34 · Cited by 159
- Authors
- Yang, M., Xie, W., Mostaghel, E., Nakabayashi, M., Werner, L., Sun, T., Pomerantz, M., Freedman, M., Ross, R., Regan, M., Sharifi, N., Figg, W. D., Balk, S., Brown, M., Taplin, M.-E., Oh, W. K., Lee, G.-S. M., & Kantoff, P. W.
- Affiliations
- Beth Israel Deaconess Medical Center (US)
- ORCID
- Venue
- Journal of Clinical Oncology
- Published
- 2011-06-20
- Volume
- 29
- Issue
- 18
- Pages
- 2565-2573
- ISSN
- 0732-183X (ISSN-L)
- 1527-7755
- PMC
- PMC3138634
- OpenAlex
- W2169468059
- Cited by
- 159
- References
- 34
- Citations by year
- 2025: 3 · 2024: 3 · 2023: 7 · 2022: 7 · 2021: 13 · 2020: 5 · 2019: 11 · 2018: 14 · 2017: 11 · 2016: 16 · 2015: 17 · 2014: 18 · 2013: 12 · 2012: 18
- FWCI
- 14.15
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Clinical Oncology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Cancer Institute (P50CA090381)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Prostate Cancer Treatment and Research
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Keywords
- SLCO2B1, SLCO1B3, androgen deprivation therapy, prostate cancer, time to progression, single nucleotide polymorphisms, pharmacogenomics, gene-gene interaction, treatment resistance
- MeSH terms
- Solute Carrier Organic Anion Transporter Family Member 1B3, Adenocarcinoma, Adult, Aged, Aged, 80 and over, Androgen Antagonists, Androgens, Biological Transport, DNA Mutational Analysis, Genotype, Humans, Gonadotropin-Releasing Hormone, Male, Middle Aged, Neoplasms, Hormone-Dependent, Orchiectomy, Prostatic Neoplasms, Testosterone, Disease Progression, Disease-Free Survival, Antineoplastic Agents, Hormonal, Drug Resistance, Neoplasm, Dehydroepiandrosterone Sulfate, Polymorphism, Single Nucleotide, Organic Anion Transporters, Organic Anion Transporters, Sodium-Independent, Kaplan-Meier Estimate
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