Polymorphisms of the androgen transporting gene SLCO2B1 may influence the castration resistance of prostate cancer and the racial differences in response to androgen deprivation

Prostate Cancer Prostatic Dis. 2013 Dec;16(4):336-40. doi: 10.1038/pcan.2013.23. Epub 2013 Jul 30.

Abstract

Background: Organic anion-transporting polypeptides (OATPs) encoded by SLCO mediate the cellular uptake of many compounds, including androgens. SLCO1B3 and SLCO2B1 are polymorphic, and single-nucleotide polymorphisms of those genes alter androgen transport efficiency. We aimed to investigate the association between genetic variations in SLCOs and the progression to castration-resistant prostate cancer (CRPC).

Methods: We studied the progression to CRPC for the SLCO1B3 rs4149117 and SLCO2B1 rs12422149 genotypes in 87 prostate cancer patients who received androgen deprivation therapy (ADT). Data were analyzed using the χ(2) test, Kaplan-Meier survival analysis and Cox proportional hazard model.

Results: SLCO3B1 genotypes were not significantly associated with the time to progression (TTP); however, patients carrying the active androgen transport SLCO2B1 genotype (GG allele) exhibited a median TTP that was 7 months shorter than that of patients with impaired androgen-transporting activity SLCO2B1 polymorphisms (GA/AA alleles) (10.0 vs 17.0 months, P=0.004). Active androgen transport genotypes of SLCO2B1 (GG allele) occurred more frequently in African and Caucasian populations than in Japanese and Han Chinese populations (P<0.001).

Conclusions: These data suggest that SLCO2B1 rs12422149 variants could provide prognostic value for prostate cancer patients treated with ADT and influence ethnic differences in response to ADT. Active androgen import may be one of the underlying mechanisms of resistance to ADT, and androgen-transporting systems could provide novel biomarkers and targets for CRPC treatment.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Alleles
  • Androgen Antagonists / therapeutic use*
  • Antineoplastic Agents, Hormonal / therapeutic use*
  • Asian Continental Ancestry Group / genetics
  • Gene Frequency
  • Genotype
  • Humans
  • Japan
  • Male
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Staging
  • Orchiectomy*
  • Organic Anion Transporters / genetics*
  • Polymorphism, Single Nucleotide*
  • Prostatic Neoplasms / genetics*
  • Prostatic Neoplasms / mortality
  • Prostatic Neoplasms / pathology
  • Prostatic Neoplasms / therapy*
  • Treatment Outcome

Substances

  • Androgen Antagonists
  • Antineoplastic Agents, Hormonal
  • Organic Anion Transporters
  • SLCO2B1 protein, human