Glutathione-S-transferase (GST) polymorphisms are associated with relapse after radical prostatectomy.
Glutathione-S-transferase (GST) polymorphisms are associated with relapse after radical prostatectomy.
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DOI：
10.1038/pcan.2012.45
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发表时间：
2013-03
影响因子：
4.8
通讯作者：
Vazquez, E.
中科院分区：
文献类型：
--
作者：
Cotignola, J.;Leonardi, D. B.;Shahabi, A.;Acuna, A. D.;Stern, M. C.;Navone, N.;Scorticati, C.;De Siervi, A.;Mazza, O.;Vazquez, E.
根治性耻骨后前列腺切除术（RRP）可以治愈器官局限性前列腺癌（PCa）；然而，一些肿瘤仍然会复发。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GSTs活性的遗传多态性可能会改变前列腺癌复发的风险。我们回顾性地招募了阿根廷接受RRP治疗的PCa患者，以研究GSTs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进行基因分型：GSTP1 c.313> G (p.105PCR-RFLP检测il >Val, rs1695)；GSTT1 null和GSTM1 null多态性。Kaplan-Meier曲线和Cox比例风险模型用于评估这些关联。GSTP1患者c.313GG基因型在未校正(风险比（HR)=3.16, 95%可信区间(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）中显示较短的生化无复发生存期（BRFS） （p=0.003）和较高的复发风险。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的基因型时，我们发现具有2个或更多风险等位基因的患者的BRFS较短（p=0.010），复发风险增加（HR=3.06, 95% CI= 1.20-7.80, p=0.019）。我们的研究结果支持GSTs基因分型在个性化治疗中的实施，作为对接受RRP的患者进行PCa管理的一种新的选择。这是阿根廷男性前列腺癌进展中首次检测GST多态性的研究。我们的研究结果在更大的队列中得到证实。
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 GSTs activities may modify the risk of PCa recurrence. We retrospectively recruited Argentine PCa patients treated with RRP to study the association between GSTs polymorphisms and PCa biochemical relapse after RRP. We genotyped germline DNA in 105 patients for: GSTP1 c.313 A>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.313 GG 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 2 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. This is the first study that examined GST polymorphisms in PCa progression in Argentine men. Replication of our findings in larger cohort is warranted.
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影响因子：
2.8
作者：
Mo, Zengnan;Gao, Yong;Jian, Lijuan
通讯作者：
Jian, Lijuan
影响因子：
3.9
作者：
Srivastava, SK;Singhal, SS;Singh, SV
通讯作者：
Singh, SV
影响因子：
2.3
作者：
To-Figueras, J;Gené, M;Corbella, J
通讯作者：
Corbella, J
影响因子：
2.8
作者：
Acevedo, C;Opazo, JL;Sepúlveda, LQ
通讯作者：
Sepúlveda, LQ
影响因子：
4.5
作者：
Corcoran, Niall M.;Hovens, Chris M.;Gleave, Martin E.
通讯作者：
Gleave, Martin E.