Ludwig Boltzmann Cluster of Urology, Medical University of Vienna, Vienna, Austria.
J Urol. 2010 Mar;183(3):878-83. doi: 10.1016/j.juro.2009.11.032. Epub 2010 Jan 18.
We outlined the putative significance of GST in renal cell carcinoma biology by investigating the influence of its deletion polymorphisms on renal cell carcinoma progression.
Genomic DNA was purified from peripheral blood leukocytes. GSTM1 and GSTT1 genes were polymerase chain reaction amplified and gene fragments were separated by agarose gel electrophoresis. Intact GSTM1 and GSTT1 alleles were identified by the presence of 230 and 480 bp fragments, respectively. Genotypes were associated with clinicopathological variables and survival.
Of 147 patients with renal cell carcinoma 80 (54%) had the GSTM1 null and 27 (18%) had the GSTT1 null genotype. The GST genotype distribution did not differ significantly from that in 112 controls without renal cell carcinoma. However, the GSTM1 null genotype was associated with 60% lower odds of the papillary subtype (OR 0.40, 95% CI 0.18 to 0.92, p = 0.032), lower Fuhrman grade (chi-square 9.77, p = 0.008) and a lower risk of metastatic disease in patients with the clear cell subtype (chi-square 4.48, p = 0.034). Of patients with the clear cell subtype those with the GSTM1 null genotype had improved cancer specific survival (p = 0.0412). GSTT1 did not correlate with any pathological variable except age at renal cell carcinoma onset since patients with renal cell carcinoma and the GSTT1 null genotype were significantly younger than their counterparts (mean +/- SD age 58.5 +/- 14.2 vs 65.4 +/- 12.8 years, p = 0.016).
GSTM1 deletion polymorphism impacts renal cell carcinoma histological subtype, Fuhrman grade and metastatic behavior while GSTT1 deletion leads to renal cell carcinoma onset at a younger age. In patients with clear cell renal cell carcinoma the GSTM1 null genotype may be associated with better prognosis.
通过研究 GST 缺失多态性对肾细胞癌进展的影响，阐述 GST 在肾细胞癌生物学中的假定意义。
从外周血白细胞中提取基因组 DNA。应用聚合酶链反应扩增 GSTM1 和 GSTT1 基因，并通过琼脂糖凝胶电泳分离基因片段。通过存在 230 和 480 bp 片段分别鉴定完整的 GSTM1 和 GSTT1 等位基因。将基因型与临床病理变量和生存相关联。
在 147 例肾细胞癌患者中，80 例（54%）具有 GSTM1 缺失基因型，27 例（18%）具有 GSTT1 缺失基因型。GST 基因型分布与 112 例无肾细胞癌的对照者无显著差异。然而，GSTM1 缺失基因型与乳头状亚型的发病几率降低 60%相关（OR 0.40，95%CI 0.18 至 0.92，p = 0.032），与 Fuhrman 分级较低（卡方 9.77，p = 0.008）和透明细胞亚型转移疾病风险较低相关（卡方 4.48，p = 0.034）。在透明细胞亚型患者中，GSTM1 缺失基因型的患者具有更好的癌症特异性生存（p = 0.0412）。GSTT1 与任何病理变量均无相关性，除了肾细胞癌发病年龄，因为具有肾细胞癌和 GSTT1 缺失基因型的患者明显比对照组年轻（平均值 +/- 标准差年龄 58.5 +/- 14.2 与 65.4 +/- 12.8 岁，p = 0.016）。
GSTM1 缺失多态性影响肾细胞癌组织学亚型、Fuhrman 分级和转移行为，而 GSTT1 缺失导致肾细胞癌发病年龄更小。在透明细胞肾细胞癌患者中，GSTM1 缺失基因型可能与更好的预后相关。
