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首页> 外文期刊>Cancer causes and control: CCC >Polymorphisms in glutathione S-transferase genes increase risk of prostate cancer biochemical recurrence differentially by ethnicity and disease severity
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Polymorphisms in glutathione S-transferase genes increase risk of prostate cancer biochemical recurrence differentially by ethnicity and disease severity

机译：谷胱甘肽S-转移酶基因的多态性按种族和疾病严重程度不同地增加前列腺癌生化复发的风险

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Objective: Genetic polymorphisms that modify the detoxifying activity of glutathione S-transferases (GSTs) can affect the level of carcinogenic metabolites created by endogenous steroid hormones and exogenous chemical substances. Although the GSTM1 null genotype has been shown to increase prostate cancer mortality in Caucasians, potential associations between GST polymorphisms and prostate cancer biochemical recurrence (BCR) have not been well studied, particularly in African-Americans. Methods: We examined potential associations between the GSTM1 null, GSTT1 null and GSTP1 Ile105Val polymorphisms and BCR, after prostatectomy, in 168 African-American and 226 Caucasian patients treated at Henry Ford Hospital in Detroit, Michigan using Cox proportional hazards modeling. Results: We found that African-Americans with the GSTT1 null genotype had increased BCR risk compared to those having GSTT1 present (hazard ratio (HR) = 2.30; 95% CI = 1.01-5.18; p = 0.04); and African-Americans with the GSTT1 null genotype and high grade tumors had an even greater risk (HR = 7.82; 95% CI = 2.49-24.50; p < 0.001). In Caucasians, an increased risk was observed in those patients with high grade tumors and the GSTM1 null genotype (HR = 2.88; 95% CI = 1.16-7.14; p = 0.02). Similar associations were observed for advanced stage and more aggressive (high grade or advanced stage) disease. Conclusion: Our results suggest GSTs may hold promise as therapeutic targets in more advanced prostate cancers, particularly, in African-Americans.
机译：目的：改变谷胱甘肽S-转移酶（GSTs）解毒活性的遗传多态性可以影响内源性类固醇激素和外源性化学物质产生的致癌代谢产物的水平。尽管已显示GSTM1无效基因型会增加白种人的前列腺癌死亡率，但尚未对GST多态性与前列腺癌生化复发（BCR）之间的潜在关联进行充分研究，尤其是在非裔美国人中。方法：我们采用Cox比例风险模型研究了密歇根州底特律亨利福特医院治疗的168名非裔美国人和226名白人患者，在前列腺切除术后检查了GSTM1 null，GSTT1 null和GSTP1 Ile105Val多态性与BCR之间的潜在关联。结果：我们发现，具有GSTT1无效基因型的非裔美国人与存在GSTT1的非裔美国人相比，BCR风险增加（危险比（HR）= 2.30; 95％CI = 1.01-5.18; p = 0.04）; GSTT1基因型无效和患有高级别肿瘤的非裔美国人则具有更高的风险（HR = 7.82; 95％CI = 2.49-24.50; p <0.001）。在高加索人中，患有高级别肿瘤和GSTM1无效基因型的患者的风险增加（HR = 2.88; 95％CI = 1.16-7.14; p = 0.02）。对于晚期和更具侵略性（高级别或晚期）疾病，观察到相似的关联。结论：我们的研究结果表明，GST有望在更晚期的前列腺癌（尤其是非裔美国人）中作为治疗靶点。

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