2123 ANDROGEN TRANSPORT GENE POLYMORPHISMS AND PROSTATE CANCER RISK AND OUTCOMES

Abstract

You have accessJournal of UrologyProstate Cancer: Markers II1 Apr 20102123 ANDROGEN TRANSPORT GENE POLYMORPHISMS AND PROSTATE CANCER RISK AND OUTCOMES Jonathan L. Wright, Elahe A. Mostaghel, Erika M. Kwon, Elaine A. Ostrander, Daniel W. Lin, and Janet L. Stanford Jonathan L. WrightJonathan L. Wright Seattle, WA More articles by this author , Elahe A. MostaghelElahe A. Mostaghel Seattle, WA More articles by this author , Erika M. KwonErika M. Kwon Bethesda, MD More articles by this author , Elaine A. OstranderElaine A. Ostrander Bethesda, MD More articles by this author , Daniel W. LinDaniel W. Lin Seattle, WA More articles by this author , and Janet L. StanfordJanet L. Stanford Seattle, WA More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2010.02.2211AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Cellular uptake of steroid hormones is facilitated by organic anion transport polypeptides. The genes SLCO2B1 and SLCO1B3 are two members of this superfamily and are involved in the transport of androgens. Variations in these genes may alter the risk of prostate cancer (PCa) and affect outcomes though altered androgen uptake. To examine this, we investigate PCa risk and outcomes associated with single nucleotide polymorphisms (SNPs) in SLCO2B1 and SLCO1B3. METHODS Participants in two population-based case-control studies were included. SNPs in SLCO2B1 and SLCO1B3 were selected from the Genome Variation Server. Risk of PCa was determined with multivariate logistic and polytomous regression for the dominant and codominant models adjusting for age, family history of PCa (FH) and PSA testing. Mortality and cause of death were determined from the SEER registry. Risk of PCSM was determined with multivariate Cox proportional hazard analysis adjusting for age, FH, PSA, Gleason sum, stage, primary treatment, BMI and smoking status. RESULTS Five SNPs from SLCO2B1 and 4 SNPs from SLCO1B3 were analyzed. Data were available for 1309 cases and 1266 controls. Carriers of either one copy (OR 0.90, 95% CI 0.75 – 1.07) or two copies (OR 0.67, 95% CI 0.43 – 1.03) of the variant A allele for SNP rs949069 in SLCO2B1 had a reduction in risk of PCa compared to homozygotes for the wild type allele (p-trend = 0.05). The median follow-up for cases was 7.0 years (range 0.77 – 16.4 years) with 64 deaths due to PCa. Carries of the variant A allele in the SLCO2B1 SNP rs12422149 had a more than 2-fold increased risk of PCSM (adjusted HR 2.07, 95% CI 1.15 – 3.71) in the dominant model. No associations with risk or PSCM were seen with SLCO1B3 SNPs. CONCLUSIONS Polymorphisms in the androgen transporter gene SLCO2B1 are associated with a reduction in the risk of PCa (SNP rs949069) and an increased risk of PCSM (SNP rs12422149). These findings underscore the complex interaction between local androgen levels and PCa and require further investigation. © 2010 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 183Issue 4SApril 2010Page: e825 Advertisement Copyright & Permissions© 2010 by American Urological Association Education and Research, Inc.MetricsAuthor Information Jonathan L. Wright Seattle, WA More articles by this author Elahe A. Mostaghel Seattle, WA More articles by this author Erika M. Kwon Bethesda, MD More articles by this author Elaine A. Ostrander Bethesda, MD More articles by this author Daniel W. Lin Seattle, WA More articles by this author Janet L. Stanford Seattle, WA More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...