Expression of SLCO Transport Genes in Castration-Resistant Prostate Cancer and Impact of Genetic Variation in SLCO1B3 and SLCO2B1 on Prostate Cancer Outcomes

被引：118

作者：

Wright, Jonathan L. ^{[1
,2
]}

Kwon, Erika M. ^{[3
]}

Ostrander, Elaine A. ^{[3
]}

Montgomery, R. Bruce ^{[4
]}

Lin, Daniel W. ^{[1
,2
]}

Vessella, Robert ^{[1
]}

Stanford, Janet L. ^{[2
,5
]}

Mostaghel, Elahe A. ^{[4
,6
]}

机构：

[1] Univ Washington, Dept Urol, Seattle, WA 98195 USA

[2] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA

[3] NHGRI, Canc Genet Branch, Bethesda, MD 20892 USA

[4] Univ Washington, Sch Publ Hlth, Dept Med, Seattle, WA 98195 USA

[5] Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA

[6] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98104 USA

来源：

CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION | 2011年 / 20卷 / 04期

关键词：

TESTOSTERONE; IDENTIFICATION; ANDROGENS; SUPPRESSION; RECEPTOR;

D O I：

10.1158/1055-9965.EPI-10-1023

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

Background: Metastases from men with castration-resistant prostate cancer (CRPC) harbor increased tumoral androgens versus untreated prostate cancers. This may reflect steroid uptake by OATP (organic anion transporting polypeptide)/SLCO transporters. We evaluated SLCO gene expression in CRPC metastases and determined whether prostate cancer outcomes are associated with single nucleotide polymorphisms (SNP) in SLCO2B1 and SLCO1B3, transporters previously shown to mediate androgen uptake. Methods: Transcripts encoding eleven SLCO genes were analyzed in untreated prostate cancer and in metastatic CRPC tumors obtained by rapid autopsy. SNPs in SLCO2B1 and SLCO1B3 were genotyped in a population-based cohort of 1,309 Caucasian prostate cancer patients. Median survival follow-up was 7.0 years (0.77-16.4). The risk of prostate cancer recurrence/progression and prostate cancer-specific mortality (PCSM) was estimated with Cox proportional hazards analysis. Results: Six SLCO genes were highly expressed in CRPC metastases versus untreated prostate cancer, including SLCO1B3 (3.6-fold; P = 0.0517) and SLCO2B1 (5.5-fold; P = 0.0034). Carriers of the variant alleles SLCO2B1 SNP rs12422149 (HR: 1.99; 95% CI: 1.11-3.55) or SLCO1B3 SNP rs4149117 (HR: 1.76; 95% CI: 1.00-3.08) had an increased risk of PCSM. Conclusions: CRPC metastases show increased expression of SLCO genes versus primary prostate cancer. Genetic variants of SLCO1B3 and SLCO2B1 are associated with PCSM. Expression and genetic variation of SLCO genes which alter androgen uptake may be important in prostate cancer outcomes. Impact: OATP/SLCO genes may be potential biomarkers for assessing risk of PCSM. Expression and genetic variation in these genes may allow stratification of patients to more aggressive hormonal therapy or earlier incorporation of nonhormonal-based treatment strategies. Cancer Epidemiol Biomarkers Prev; 20(4); 619-27. (C) 2011 AACR.

引用

页码：619 / 627

页数：9

共 34 条

[1]

Al Sarakbi W, 2006, ANTICANCER RES, V26, P4985

[2]

Transporter gene expression in lactating and nonlactating human mammary epithelial cells using real-time reverse transcription-polymerase chain reaction [J].