缺氧誘導因子其基因多型性與肝細胞癌的相關性探討

肝細胞癌 (hepatocellular carcinoma; HCC)是世界各地主要的癌症死亡原因之一。在台灣男性中，它也是癌症死亡原因的第一位，也高居女性的第二順位。在近年來的統計研究中也發現，肝細胞癌的死亡率也有逐年增加的趨勢。而有許多的研究報告指出，單核苷基因多型性 (Single Nucleotide Polymorphism; SNP) 被認為與肝細胞癌的罹患風險有關，也可以當作一個預測因子。而在肝細胞癌形成過程中，與腫瘤微環境缺氣(hypoxia)有很大的相關性，但是缺氧誘導因子-1α(hypoxia-inducible factor-1α; HIF-1α)的基因多型性與肝細胞癌的相關性卻仍不清楚。因此，本研究的目的想要評估HIF-1α的兩個基因多型性C1772T和G1790A和罹患肝細胞癌及其臨床病理狀態之可能潛在相關性。本研究利用聚合酶連鎖反應限制片段長度分析(PCR-RFLP)的方式，針對347位的健康對照組與102位的肝細胞癌患者，觀察其HIF-1α基因多型性C1772T和G1790A的狀態並評估其對於肝細胞癌之相關性。經與健康對照組的受試者比對後發現，在調整了其他干擾因子之後，HIF-1αG1790A位置若存在GA此基因型，與GG基因型有較高罹患肝細胞癌的風險(AOR＝3.97；95% CI＝1.70-9.22)，這也意味著肝細胞癌易感性和HIF-1αG1790A的基因多型性存在著有意義相關。此外研究結果也透露HIF-1αG1790A的基因多型性和環境危險因子如香菸或酒精的使用有協同作用。然而HIF-1α的基因多型性與肝細胞癌的不同腫瘤大小或不同時期或轉移與否等臨床指標皆無明顯的相關性。因此，我們發現HIF-1α其G1790A基因多型性是決定肝細胞癌易感性之重要因子。而此基因多型性與香菸及酒精使用的交互作用可顯著地增加肝細胞癌形成風險。

關鍵字

肝細胞癌；單核苷基因多型性；缺氧誘導因子

並列摘要

Hepatocellular carcinoma (HCC) is one of the most frequent malignant neoplasms worldwide and is the second leading cause of cancer death in Taiwan. The aim of this study was to examine the potential associations of two hypoxia inducible factor-1α (HIF-1α) gene polymorphisms, C1772T and G1790A, with the susceptibility and clinicopathological status of hepatocellular carcinoma. A total of 449 subjects, including 347 healthy controls and 102 patients with hepatocellular carcinoma, were recruited in this study and subjected to polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analyses to estimate the impact of these two polymorphic variants on hepatocellular carcinoma. G1790A heterozygotes showed a higher risk for hepatocellular carcinoma, compared to GG genotypes after adjusting for other confounders (AOR=3.97; 95%CI=1.70-9.22), indicating a significant association between hepatocellular carcinoma susceptibility and G1790A polymorphism. Moreover, results also revealed the presence of synergistic effect between gene polymorphism of HIF-1α G1790A and environmental risk factors, such as tobacco and alcohol consumptions while there was no significant association between HIF-1α gene polymorphism and clinicopathological parameters of hepatocellular carcinoma. In conclusions, genetic polymorphism at G1790A of HIF-1α is an important factor for determining the susceptibility to hepatocellular carcinoma. The interaction effects of G1790A heterozygotes to tobacco and to alcohol consumption significantly increase the risk to develop hepatocellular carcinoma.

並列關鍵字

hypoxia inducible factor-1 ； hepatocellular carcinoma ； polymorphism

參考文獻

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國際替代計量

缺氧誘導因子其基因多型性與肝細胞癌的相關性探討

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