IL-18基因多型性對肝癌的易感性和臨床病理之相關性研究

Association between interleukin-18 polymorphisms and hepatocellular carcinoma occurrence and clinical progression

劉漢傑(Hon-Kit Lau)

指導教授 ： 楊順發

中山醫學大學/醫學院/醫學研究所/博士(2017年)

摘要

肝癌在世界各地為一種日益嚴重之惡性腫瘤疾病。在台灣，根據2017年衛生福利部所公布的統計數據顯示，惡性腫瘤在死亡原因中高居首位，且肝癌在所有癌症死亡人數中佔第二位。介白質素-18 (interleukin-18，IL-18)，被認為能促進發炎反應，另外也有研究指出在癌症發展過程中，IL-18是腫瘤細胞生成因素之一。此外，IL-18基因多型性和發炎性疾病及自體免疫性疾病有關。而目前IL-18基因多型性與肝癌之間的研究還不明確。因此，本實驗想要探討IL-18 (rs1976518 & rs187238) 兩者基因多型性和肝癌易感性與其臨床病理參數，包括臨床分期、腫瘤大小、淋巴結轉移、細胞分化狀態等可能潛在相關性。本實驗利用即時定量聚合酶連鎖反應方法，針對559位健康對照組與342位肝癌患者，觀察其IL-18基因多型性，評估與肝癌的罹患易感性。經與健康對照組的受試者比對後發現，IL-18 (rs187238) 攜帶有一個C對偶基因頻率與肝癌發生率有關 (p < 0.05)，基因型G/C+C/C的人比基因型G/G的人有1.987倍的機率罹患肝癌(95% CI: 1.301-3.032, p < 0.05)；在肝癌患者中，IL-18 (rs187238) 攜帶有G/C+C/C基因的患者，造成罹患B型肝炎機率是攜帶G/G基因型的1.668倍(95% CI: 1.001-2.786, p < 0.05)。因此本篇研究認為，IL-18 (rs187238) 基因多型性，攜帶C對偶基因頻率與台灣人族群罹患肝癌的易感性有關，可視為肝癌發生以及感染B型肝炎的可能因子。

關鍵字

肝癌 ； 介白質素-18 ； 基因多型性

並列摘要

Liver cancer is growing problem of malignant disease worldwide and is the second leading ause of cancer death in Taiwan. The aim of this study was to examine the potential association of interleukin-18 (IL-18) polymorphisms with the susceptibility and clinicopathological status of hepatocellular carcinoma. A total of 901 subjects, including 559 controls and 342 patients with hepatocellular carcinoma, were recruited in this study and subjected to polymerase chian reaction- restriction fragment length polymorphism (PCR-RFLP) analysis to estimate the impact of this polymorphism variant. This experimental evidence shows that individuals with at least 1 varied C allele of rs187238 (IL-18 polymorphism) had a 1.987-fold risk (95% confidence interval [CI] = 1.301-3.032, p < 0.05) of developing hepatocellular carcinoma compared to patients with the wild-type G/G homozygote. Hepatocellular carcinoma patients with at least 1 varied C allele of rs187238 had a 1.668-fold risk of HBsAg positive compared to patients with the wild-type G/G homozygote. In conclusions, the varied C allele of the IL-18 gene may be considered a factor contributing to increased susceptibility, and may be a predictive factor for infected with HBV in Taiwanese with hepatocellular carcinoma.

並列關鍵字

Liver cancer ； interleukin-18 ； Gene polymorphism

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