Prognostic Assessment of Three Single-Nucleotide Polymorphisms (GNB3 825C>T, BCL2-938C>A, MCL1-386C>G) in Extrahepatic Cholangiocarcinoma
Prognostic Assessment of Three Single-Nucleotide Polymorphisms (GNB3 825C>T, BCL2-938C>A, MCL1-386C>G) in Extrahepatic Cholangiocarcinoma
复制标题
DOI：
10.3109/07357900903095714
复制
发表时间：
2010-06-01
影响因子：
2.4
通讯作者：
Canbay, Ali
中科院分区：
文献类型：
--
作者：
Fingas, Christian Dominik;Katsounas, Antonios;Canbay, Ali
背景/目的：胆管细胞癌（CCA）具有毁灭性的预后，而能够精确预测临床结果的标志物长期以来仍然稀缺。最近，已经证明调节 G 蛋白信号转导和细胞凋亡的基因中几个单核苷酸多态性 (SNP) 的基因型分布可以作为各种癌症的有用预测参数。我们的目的是扩展适合预测 CCA 结果的 SNP 组。方法：对 40 名患有肝外 CCA 的白人患者和 40 名年龄和性别匹配的健康白种人进行基因分型，以阐明临床结果与以下三种 SNP 基因型之间的假定关联：G 蛋白 β 3 (GNB3) 825C>T、B 细胞淋巴瘤-2 (Bcl-2) -938C>A 和骨髓细胞白血病-1 (Mcl-1) -386C>G。结果：与显示 CT 或 TT 基因型的患者相比，GNB3 825C>T 多态性 C 等位基因纯合的患者表现出显着延长的总生存期（中位生存期[月]：31 vs. 13 vs. 7；p < .05），并且还表现出较低的胆红素血清水平。此外，BCL2-938C>A 多态性的 CC 基因型与较高的 GLDH 血清活性相关（U/l；29.8 +/- 7.1 对比 11.4 +/- 4.3 对比 5.6 +/- 1.7，比较 CC、CA 与 AA；p < .05）。所有 SNP 的基因型分布在患者与对照组中没有显着差异。结论：GNB3 825C>T SNP 可能是 CC 基因型肝外 CCA 患者的一种新型独立预后标志物，与良好的临床结果相关。需要进一步的前瞻性研究来证实这些结果并揭示其他功能性 SNP 效应。
Background/Aims: Cholangiocellular carcinoma (CCA) has a devastating prognosis and markers enabling a precise prediction of the clinical outcome have long remained scarce. Recently, it has been demonstrated that genotype distribution of several single-nucleotide polymorphisms (SNPs) in genes that modulate G protein-signal transduction and apoptosis can serve as helpful predictive parameters in various carcinomas. We here aimed at extending the panel of SNPs suitable for predicting the outcome of CCA. Methodology: Forty Caucasian patients with extrahepatic CCA and 40 age-and sex-matched healthy white Caucasians were genotyped to elucidate putative associations between clinical outcome and genotypes of the three following SNPs: G protein beta 3 (GNB3) 825C>T, B-cell-lymphoma-2 (Bcl-2) -938C>A, and myeloid cell leukemia-1 (Mcl-1) -386C>G. Results: Patients homozygous for the C allele of the GNB3 825C>T polymorphism exhibited a significant prolonged overall survival compared with patients displaying the CT or TT genotype (median survival [months]: 31 vs. 13 vs. 7; p < .05) and also showed lower bilirubin serum levels. Additionally, the CC genotype of the BCL2-938C>A polymorphism was associated with higher GLDH serum activities (U/l; 29.8 +/- 7.1 vs. 11.4 +/- 4.3 vs. 5.6 +/- 1.7 comparing CC vs. CA vs. AA; p < .05). Genotype distributions for all SNPs were not significantly different in patients vs. controls. Conclusions: GNB3 825C>T SNP may be a novel independent prognostic marker for patients suffering from extrahepatic CCA with the CC genotype to be associated with a favorable clinical outcome. Further prospective studies are needed to confirm these results and reveal additional functional SNP effects.