Dana-Farber Cancer Institute, Dana 710B, 44 Binney St, Boston, MA 02115.
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.
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.
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).
Genetic variants of SLCO2B1 and SLCO1B3 may function as pharmacogenomic determinants of resistance to ADT in prostate cancer.
Written by:
Yang M, Xie W, Mostaghel E, Nakabayashi M, Werner L, Sun T, Pomerantz M, Freedman M, Ross R, Regan M, Sharifi N, Figg WD, Balk S, Brown M, Taplin ME, Oh WK, Lee GS, Kantoff PW. Are you the author?
Reference: J Clin Oncol. 2011 Jun 20;29(18):2565-73.
doi: 10.1200/JCO.2010.31.2405
PubMed Abstract
PMID: 21606417
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