TY - JOUR
T1 - SLCO2B1 and SLCO1B3 may determine time to progression for patients receiving androgen deprivation therapy for prostate cancer
AU - Yang, Ming
AU - Xie, Wanling
AU - Mostaghel, Elahe
AU - Nakabayashi, Mari
AU - Werner, Lillian
AU - Sun, Tong
AU - Pomerantz, Mark
AU - Freedman, Matthew
AU - Ross, Robert
AU - Regan, Meredith
AU - Sharifi, Nima
AU - Figg, William Douglas
AU - Balk, Steven
AU - Brown, Myles
AU - Taplin, Mary Ellen
AU - Oh, William K.
AU - Lee, Gwo Shu Mary
AU - Kantoff, Philip W.
PY - 2011/6/20
Y1 - 2011/6/20
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=79959294088&partnerID=8YFLogxK
U2 - 10.1200/JCO.2010.31.2405
DO - 10.1200/JCO.2010.31.2405
M3 - Article
C2 - 21606417
AN - SCOPUS:79959294088
SN - 0732-183X
VL - 29
SP - 2565
EP - 2573
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 18
ER -