Department of Biological Chemistry, School of Sciences, University of Buenos Aires-IQUIBICEN, CONICET, Buenos Aires, Argentina.
Prostate Cancer Prostatic Dis. 2013 Mar;16(1):28-34. doi: 10.1038/pcan.2012.45. Epub 2012 Nov 13.
Organ confined prostate cancer (PCa) can be cured by radical retropubic prostatectomy (RRP); however, some tumors will still recur. Current tools fail to identify patients at risk of recurrence. Glutathione-S-transferases (GSTs) are involved in the metabolism of carcinogens, hormones and drugs. Thus, genetic polymorphisms that modify the GST activities may modify the risk of PCa recurrence.
We retrospectively recruited Argentine PCa patients treated with RRP to study the association between GST polymorphisms and PCa biochemical relapse after RRP. We genotyped germline DNA in 105 patients for: GSTP1 c.313A>G (p.105 Ile>Val, rs1695) by PCR-RFLP; and GSTT1 null and GSTM1 null polymorphisms by multiplex PCR. Kaplan-Meier curves and Cox proportional hazard models were used to evaluate these associations.
Patients with GSTP1 c.313GG genotype showed shorter biochemical relapse-free survival (BRFS) (P = 0.003) and higher risk for recurrence in unadjusted (Hazard ratio (HR) = 3.16, 95% confidence interval (95% CI) = 1.41-7.06, P = 0.005) and multivariate models (HR = 3.01, 95% CI = 1.13-8.02, P = 0.028). We did not find significant associations for GSTT1 and GSTM1 genotypes. In addition, we found shorter BRFS (P = 0.010) and increased risk for recurrence for patients having two or more risk alleles when we combined the genotypes of the three GSTs in multivariate models (HR = 3.06, 95% CI = 1.20-7.80, P = 0.019).
Our results give support to the implementation of GSTs genotyping for personalized therapies as a novel alternative for PCa management for patients who undergo RRP. To the best of our knowledge, this is the first study that examined GST polymorphisms in PCa progression in Argentine men. Replication of our findings in larger cohort is warranted.
局限性前列腺癌（PCa）可以通过根治性前列腺切除术（RRP）治愈；然而，有些肿瘤仍会复发。目前的工具无法识别有复发风险的患者。谷胱甘肽-S-转移酶（GSTs）参与致癌物、激素和药物的代谢。因此，改变 GST 活性的遗传多态性可能会改变 PCa 复发的风险。
我们回顾性招募了接受 RRP 治疗的阿根廷 PCa 患者，以研究 GST 多态性与 RRP 后 PCa 生化复发之间的关系。我们对 105 例患者的种系 DNA 进行了 GSTP1 c.313A>G（p.105 Ile>Val，rs1695）的 PCR-RFLP 基因分型；以及 GSTT1 缺失和 GSTM1 缺失多态性的多重 PCR 基因分型。使用 Kaplan-Meier 曲线和 Cox 比例风险模型来评估这些关联。
携带 GSTP1 c.313GG 基因型的患者生化无复发生存（BRFS）较短（P=0.003），且未校正（危险比（HR）=3.16，95%置信区间（95%CI）=1.41-7.06，P=0.005）和多变量模型（HR=3.01，95%CI=1.13-8.02，P=0.028）中复发风险更高。我们没有发现 GSTT1 和 GSTM1 基因型的显著相关性。此外，当我们在多变量模型中结合三种 GST 基因型时，我们发现 BRFS 更短（P=0.010），且携带两个或更多风险等位基因的患者复发风险更高（HR=3.06，95%CI=1.20-7.80，P=0.019）。
我们的结果支持对接受 RRP 治疗的患者进行 GST 基因分型以实现个体化治疗，作为 PCa 管理的新方法。据我们所知，这是第一项研究 GST 多态性在阿根廷男性 PCa 进展中的研究。需要在更大的队列中复制我们的研究结果。
