SLCO2B1 和 SLCO1B3 可能决定接受雄激素剥夺疗法治疗前列腺癌的患者的进展时间。
SLCO2B1 and SLCO1B3 may determine time to progression for patients receiving androgen deprivation therapy for prostate cancer.
机构信息
Dana-Farber Cancer Institute, Harvard Medical School, Dana 710B, 44 Binney St., Boston, MA 02115, USA.
出版信息
J Clin Oncol. 2011 Jun 20;29(18):2565-73. doi: 10.1200/JCO.2010.31.2405. Epub 2011 May 23.
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.
摘要
目的
雄激素剥夺疗法（ADT）是治疗晚期前列腺癌的重要手段，但疗效差异较大。我们假设雄激素转运体基因 SLCO2B1 和 SLCO1B3 的遗传变异可能决定 ADT 的进展时间。
方法
对 538 例接受 ADT 治疗的前列腺癌患者进行了 SLCO2B1 和 SLCO1B3 单核苷酸多态性（SNP）的基因分型。通过生化测定研究了 SLCO2B1 编码 SNP 在转运雄激素方面的生物学功能。
结果
SLCO2B1 中的 3 个 SNP 与 ADT 的进展时间（TTP）相关（P<.05）。这些多态性的中位 TTP 差异约为 10 个月。允许雄激素更有效输入的 SLCO2B1 基因型增强细胞生长，并与 ADT 的 TTP 缩短相关。同时携带 SLCO2B1 和 SLCO1B3 基因型（可更有效地输入雄激素）的患者，ADT 的中位 2 年 TTP 缩短了 2 年，表明存在基因-基因相互作用（P（交互）=.041）。
结论
SLCO2B1 和 SLCO1B3 的遗传变异可能是前列腺癌对 ADT 耐药的药物基因组决定因素。
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