SLCO2B1 and SLCO1B3 May Determine Time to Progression for Patients Receiving Androgen Deprivation Therapy for Prostate Cancer

Overview

Journal J Clin Oncol

Specialty Oncology

Date 2011 May 25

PMID 21606417

Citations 92

Authors

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

Affiliations

Soon will be listed here.

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 (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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