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谷胱甘肽硫转移酶 T1(GSTT1)、谷胱甘肽 S-转移酶 M1(GSTM1)和细胞色素 P4501B1(CYP1B1)基因多态性与散发性肾细胞癌易感性的关系。

GSTT1, GSTM1, and CYP1B1 gene polymorphisms and susceptibility to sporadic renal cell cancer.

机构信息

Department of Urology, Hospital and University Complex of Albacete, Albacete, Spain.

出版信息

Urol Oncol. 2012 Nov-Dec;30(6):864-70. doi: 10.1016/j.urolonc.2010.10.001. Epub 2011 Apr 1.

Abstract

PURPOSE

To estimate the prevalence and importance of GSTT1, GSTM1, and CYP1B1 genotypes in renal cell carcinoma (RCC), and to identify their value as a prognostic factor.

MATERIALS AND METHODS

Cross-sectional study of a group of patients diagnosed with RCC (n = 133) and a control group (n = 208) with benign conditions and no history of tumor. Controls were selected by cumulative samples and mixed pairing. All subjects pertained to the catchment area for our hospital. Sociodemographic variables, anatomical pathology features, and presence of GSTT1, GSTM1, and CYP1B1 polymorphisms by multiplex PCR and sequencing techniques.

RESULTS

There were no differences in the genotype distribution of the GSTT1 and GSTM1 genes between cases and controls. In the case of CYP1B1, the GG genotype (Ala119) was more prevalent in patients with RCC (OR = 2.08; 95% CI: 1.32-2.28) and may be implicated in 34.3% (95% CI: 16.3-52.2) of RCCs. In patients with GSTT1 deletion, TNM stages III to IV were more common (39.1%); whereas in Val432 homozygous patients in CYP1B1, Fuhrman grades 3 to 4 (54.6%) were more common. Because this was a cross-sectional study, longitudinal studies are needed in the future to confirm these data.

CONCLUSIONS

No relationship between GSTT1 and GSTM1 genotypes and RCC risk was observed. Homozygous subjects with Ala119 in CYP1B1 had twice the risk of RCC as homozygous for Ser119 or heterozygotes. Patients with GSTT1 deletion had tumors of more advanced stages, and those with Val432 polymorphism in CYP1B1 had tumors of higher Fuhrman grade.

摘要

目的

评估 GSTT1、GSTM1 和 CYP1B1 基因型在肾细胞癌 (RCC) 中的流行程度和重要性,并确定它们作为预后因素的价值。

材料和方法

这是一项对一组确诊为 RCC(n = 133)的患者和一组无肿瘤病史的良性疾病对照组(n = 208)的病例对照研究。对照组通过累积样本和混合配对选择。所有受试者均来自我们医院的服务区。进行了社会人口统计学变量、解剖病理学特征以及 GSTT1、GSTM1 和 CYP1B1 多态性的多重 PCR 和测序技术检测。

结果

病例组和对照组 GSTT1 和 GSTM1 基因的基因型分布无差异。在 CYP1B1 方面,RCC 患者 GG 基因型(Ala119)更为常见(OR = 2.08;95%CI:1.32-2.28),可能与 34.3%(95%CI:16.3-52.2)的 RCC 相关。GSTT1 缺失的患者中,III 期至 IV 期更为常见(39.1%);而 CYP1B1 中 Val432 纯合子患者,Fuhrman 分级 3 至 4 级更为常见(54.6%)。由于这是一项横断面研究,未来需要进行纵向研究来证实这些数据。

结论

未观察到 GSTT1 和 GSTM1 基因型与 RCC 风险之间存在关联。CYP1B1 中 Ala119 纯合子的患者患 RCC 的风险是 Ser119 或杂合子的两倍。GSTT1 缺失的患者肿瘤分期更晚,而 CYP1B1 中 Val432 多态性的患者肿瘤 Fuhrman 分级更高。

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