Glucose metabolism gene polymorphisms and clinical outcome in pancreatic cancer.
Glucose metabolism gene polymorphisms and clinical outcome in pancreatic cancer.
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DOI：
10.1002/cncr.25612
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发表时间：
2011-02-01
期刊：
影响因子：
6.2
通讯作者：
Li, Donghui
中科院分区：
文献类型：
--
作者：
Dong, Xiaoqun;Tang, Hongwei;Hess, Kenneth R.;Abbruzzese, James L.;Li, Donghui
关键词：
葡萄糖代谢改变是恶性肿瘤最常见的代谢标志。我们测试了葡萄糖代谢基因变异影响胰腺癌临床结果的假设。我们回顾性地对 154 名局部疾病患者的 5 个葡萄糖代谢基因的 26 个单核苷酸多态性 (SNP) 进行了基因分型，并在 552 名不同阶段的胰腺腺癌患者中验证了结果。使用多变量 Cox 比例风险回归模型并调整临床预测因子来评估基因型和总生存期 (OS) 之间的关联。在 154 名患者的训练集中，葡萄糖激酶 (GCK) IVS1+9652C>T 和己糖激酶 (HK)2 N692N 纯合变异与 OS 降低显着相关 (P < 0.001)。这些关联在 552 名患者的验证集和所有 706 名患者的组合数据集中得到了证实 (P ≤ 0.001)。此外，HK2 R844K 变异 K 等位基因与验证集和组合数据集中更好的生存相关（P ≤ 0.001）。按疾病分期进一步分析数据时，局部疾病患者的谷氨酰胺-果糖-6-磷酸转氨酶 (GFPT1) IVS14-3094T>C、HK2 N692N 和 R844K，以及晚期疾病患者的 GCK IVS1+9652C>T 是 OS 的显着独立预测因子 (P ≤ 0.001)。 GPI 的单倍型 CGG 和 HK2 的 GCTATGG 分别与更好的 OS 相关，P 值为 0.004 和 0.007。我们证明葡萄糖代谢基因多态性影响胰腺癌的临床结果。这些观察结果支持异常的葡萄糖代谢在胰腺癌发生中的作用。
Altered glucose-metabolism is the most common metabolic hallmark of malignancies. We tested the hypothesis that glucose-metabolism gene variations affect clinical outcome in pancreatic cancer. We retrospectively genotyped 26 single nucleotide polymorphisms (SNPs) from 5 glucose-metabolism genes in 154 patients with localized disease and validated the findings in 552 patients with different stages of pancreatic adenocarcinoma. Association between genotypes and overall survival (OS) was evaluated using multivariable Cox proportional hazard regression models with adjustment for clinical predictors. Glucokinase (GCK) IVS1+9652C>T and hexokinase (HK)2 N692N homozygous variants were significantly associated with reduced OS in the training set of 154 patients (P < 0.001). These associations were confirmed in the validation set of 552 patients and in the combined dataset of all 706 patients (P ≤ 0.001). In addition, HK2 R844K variant K allele was associated with a better survival in the validation set and the combined dataset (P ≤ 0.001). When data was further analyzed by disease stage, glutamine-fructose-6-phosphate transaminase (GFPT1) IVS14-3094T>C, HK2 N692N and R844K in patients with localized disease, and GCK IVS1+9652C>T in patients with advanced disease were significant independent predictors for OS (P ≤ 0.001). Haplotype CGG of GPI and GCTATGG of HK2 were associated with better OS, respectively, with a P value of 0.004 and 0.007. We demonstrated that glucose-metabolism gene polymorphisms affect clinical outcome in pancreatic cancer. These observations support a role of abnormal glucose metabolism in pancreatic carcinogenesis.
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