SLCO2B1 and SLCO1B3 may determine time to progression for patients receiving androgen deprivation therapy for prostate cancer

Ming Yang, Wanling Xie, Elahe Mostaghel, Mari Nakabayashi, Lillian Werner, Tong Sun, Mark Pomerantz, Matthew Freedman, Robert Ross, Meredith Regan, Nima Sharifi, William Douglas Figg, Steven Balk, Myles Brown, Mary Ellen Taplin, William K. Oh, Gwo Shu Mary Lee, Philip W. Kantoff

Research output: Contribution to journalArticle

120 Scopus citations

Abstract

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 (Pinteraction = .041). Conclusion: Genetic variants of SLCO2B1 and SLCO1B3 may function as pharmacogenomic determinants of resistance to ADT in prostate cancer.

Original languageEnglish (US)
Pages (from-to)2565-2573
Number of pages9
JournalJournal of Clinical Oncology
Volume29
Issue number18
DOIs
StatePublished - Jun 20 2011

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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