WWOX基因多型性與肺癌患者其EGFR突變的相關性探討

中山醫學大學機構典藏 CSMUIR > 醫學院 > 醫學研究所 > 博碩士論文 > Item 310902500/19676

Please use this identifier to cite or link to this item: https://ir.csmu.edu.tw:8080/ir/handle/310902500/19676

Title:	WWOX基因多型性與肺癌患者其EGFR突變的相關性探討 Study of the association between WWOX polymorphism in lung cancer with epidermal growth factor receptor mutation
Authors:	林芷芸 Lin, Chih-Yun
Contributors:	中山醫學大學:醫學研究所;張耀仁;楊順發
Keywords:	WWOX;表皮生長因子;肺癌;基因多型性 Epidermal growth factor receptor (EGFR);single nucleotide polymorphism (SNP);WWOX;lung cancer
Date:	2018
Issue Date:	2019-01-04T04:44:38Z (UTC)
Abstract:	肺癌（lung cancer）是全球發生率最高的癌症，根據衛生福利部統計，105年主要癌症死亡原因第一名就是氣管、支氣管及肺癌。目前醫界已知道分子標靶治療，如表皮生長因子受體（Epidermal growth factor receptor，簡稱EGFR）抑制劑，應使用於特定的肺癌病患。而EGFR抑制劑的治療效果又與癌細胞EGFR突變有關。WW domain containing oxidoreductase（WWOX）基因位於16q23.3-24.1的位置，在多種的癌症中常發現此斷裂基因造成異質染色體的缺失，因此WWOX基因被定義為腫瘤抑制基因。過去的研究已證實WWOX的基因多型性與癌症風險有關，而EGFR的突變型態又與肺癌的治療相關。本研究分析肺癌病人攜帶WWOX 不同基因多型性與其EGFR突變之間的相關性，並探討其與臨床病理特徵等指標的相關性分析。在本研究中收集316位肺癌病人的血液萃取DNA，利用real-time PCR genotype的分析方式探討WWOX基因多型性與肺癌患者其EGFR突變的相關性。研究中觀察WWOX基因中rs11545028、rs12918952、rs3764340、rs73569323及rs383362等五種多型性的變異，並合併以上這些基因表現去釐清WWOX的基因多型性對於肺癌患者所造成的影響，分析WWOX基因多型性與肺癌患者EGFR突變的相關性，並探討其與臨床病理特徵等指標的相關性。研究結果發現，WWOX基因的多型性在EGFR突變與否的肺癌個案皆無顯著相關，但進一步分析發現，rs3764340攜帶CC與CG+GG的變異對於EGFR突變的肺癌患者在淋巴結轉移的狀態上有顯著差異，特別對於在EGFR L858R突變的肺癌患者在腫瘤型態與淋巴結轉移的狀態上有顯著差異。另外，比較rs73569323攜帶CC與CT+TT的變異對於EGFR L858R突變的肺癌患者在腫瘤型態有顯著差異。研究結果證明WWOX基因的多型性與EGFR突變，特別是L858R突變的肺癌患者其腫瘤型態與淋巴結轉移的狀態相關。 Lung cancer is the leading cause of death from cancer. Epidermal growth factor receptor (EGFR) inhibitor, a molecular targeted therapy, treatment for specific patients of lung cancer. The treatment effect of EGFR-tyrosine kinase inhibitor (EGFR-TKI) is related to the EGFR mutations of cancer cells. Several studies have indicated that the mutations of EGFR are common in lung adenocarcinomas, especially in female lung cancer patients with never-smoking history. The human WW domain-containing oxidoreductase (WWOX) gene located on chromosome 16q23.3-24.1, one of the most active fragile sites. WWOX gene has been identified as a tumor suppressor gene due to a high frequency of LOH (loss of heterozygosity) in tumors. It was reported that WWOX single nucleotide polymorphisms (SNPs) are associated with cancer. Our hypothesis suggests that the gene variations in WWOX are associated with EGFR mutations of lung cancer. Five SNPs, including rs11545028, rs12918952, rs3764340, rs73569323 and rs383362, of WWOX gene were observed from 316 patients with lung cancer. The clinical and pathological characteristics data, including age, gender, smoking status, TNM staging, and EGFR mutation status were recorder. The results indicated that WWOX rs3764340 polymorphism carrying G allele was significant associated with lymph node metastasis in lung cancer patients with EGFR mutation. Especially the associations between lymph node metastasis and tumor status in lung cancer patients with EGFR L858R point mutation were significant. In addition, rs73569323 carring T allele was significant associated with tumor status of EGFR L858R mutation lung cancer patients. The results of the study demonstrated that the polymorphism of WWOX is associated with the tumor status and lymph node metastasis in lung cancer patients with EGFR mutations, particularly L858R point mutations.
URI:	https://ir.csmu.edu.tw:8080/ir/handle/310902500/19676
Appears in Collections:	[醫學研究所] 博碩士論文

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