穀胱甘肽硫轉移酵素之基因多型性與肝細胞癌之相關性探討

肝細胞癌 (hepatocellular carcinoma; HCC)目前是全世界常見的惡性腫瘤之一。在台灣地區，每年也是在癌症死亡率的前幾名。而有諸多研究報告曾指出，基因的多型性 (Single Nucleotide Polymorphism; SNP) 被認為與罹患惡性腫瘤的風險有關，也可以當作一個預測因子。而之前有文獻曾指出，在肝細胞癌腫瘤細胞增殖、血管新生與腫瘤細胞轉移上，穀胱甘肽硫轉移酵素異構酶(Glutathione S-transferases theta and mu) 扮演著重要的角色。因此，本研究之目的，即在於評估在穀胱甘肽硫轉移酵素異構酶的基因多型性與罹患肝細胞癌的風險及其與臨床病理狀態的相關性。本研究利用聚合酶鏈限制性連鎖反應的方式，針對三百八十六位的健康對照組與一百零二位的肝細胞癌患者，進行這些受測者的GSTT1及GSTM1之基因多型性分析。經與健康對照組的受試者比對後發現，在小於56歲的族群中，肝細胞癌患者若存在GSTT1的基因，經由校正不同比對因子後，則至少有2.77倍的高風險 (95% CI: 1.09-7.09)會誘發成肝細胞癌，但是與誘發成肝細胞癌的不同腫瘤大小或不同時期或轉移與否皆無明顯的相關性。然而，GSTM1的基因多型性與罹患肝細胞癌風險或不同的病理狀態中都沒有明顯的相關性。因此，我們可以發現，在小於56歲的族群中，GSTT1的基因多型性可被視為促進肝細胞癌的發生與其病理上發展成肝細胞癌之相關因子。以本研究的結果，推論在小於56歲的肝細胞癌患者中，諸多造成肝細胞癌的因子中，與GSTT1的基因多型性有關，而與GSTM1基因多型性無關。因此，希望可以將GSTT1的基因多型性應用到肝細胞癌中，並期許可以當作一個診斷或追蹤肝細胞癌的輔助因子。

Hepatocellular carcinoma (HCC) is one of the most frequent malignant neoplasms worldwide and is the second leading cause of cancer death in Taiwan. Genetic polymorphism has been reported as a factor for increased susceptibility of hepatocellular carcinoma. Glutathione S-transferases theta (GSTT1) and mu (GSTM1) play essential roles in detoxification of ingested xenobiotics and modulation of the susceptibility of gene-related cancer. The aim of this study was to estimate the relationships between these two gene polymorphisms and hepatocellular carcinoma risk and clinicopathological status in Taiwanese. Polymerase chain reaction (PCR) was used to determine gene polymorphisms of 102 patients with hepatocellular carcinoma and 386 healthy controls. Both gene polymorphisms were not associated with the clinical pathological status of hepatocellular carcinoma and serum levels of liver-related clinical pathological markers. While no relationship between GSTM1 gene polymorphism and HCC susceptibility was found, individuals of age < 56 years old with GSTT1 present genotype had a risk of 2.77 fold (95% CI: 1.09-7.09) for hepatocellular carcinoma compared to that with null variant, after adjustment for other confounders. GSTT1 and GSTM1 null genotypes do not associate with increased risk of hepatocellular carcinoma.