腫瘤壞死因子之基因標記多型性與口腔鱗狀細胞癌之相關性研究

Association Between Genetic Polymorphism of Tumor Necrosis Factor-alpha and Risk of Oral Squamous Cell Carcinoma

李嘉鐸(Chia-Tuo Lee)

指導教授 ： 謝天渝 ； 張基隆

高雄醫學大學/口腔醫學院/牙醫學研究所/碩士(2005年)

摘要

口腔癌在台灣地區已是攸關國人健康的重要課題。根據之前的研究，口腔癌患者之TNF-α血清濃度明顯升高；而mRNA表現之相對強度亦有增加趨勢。本研究期望了解TNF-α於基因層級，在口腔癌致病機制中所扮演的角色。
　　本研究取樣含158名口腔癌患者及111名高雄市清潔隊員，全為男性，經問卷調查後抽取靜脈血以萃取DNA，針對TNF-α促進子上-238、-308，及-1031三個位置進行PCR-RFLP，實驗結果以t檢定、卡方檢定，及多元邏輯複迴歸分析之。
　　在不加入任何條件下，除-238之其餘位置基因型分佈都與對照組呈顯著差異；其中TNF-238 AA在兩組中皆不存在；-1031在兩組間有顯著差異，但基因型分佈頗為類似；值得注意的是，口腔癌患者之-308A明顯偏多，-308G則較健康人少，表示-308G可能具有對抗口腔癌之保護機制，而-308A則可能促進口腔癌之發生。此外，不論有無使用檳榔、菸、酒，僅-308於兩組間皆呈顯著差異，而-238僅在無喝酒經驗者中兩組有差異，其餘則皆無顯著差異。考慮各位置對於罹患口腔癌之風險，結果僅-308與-1031之變異為顯著之危險因子。
TNF-α基因位於人類MHC，為哺乳類基因體中最具多型性者，如此頻繁的多型性是否與口腔癌之發生有其相關？值得深入研究。

關鍵字

基因標記多型性 ； 腫瘤壞死因子 ； 口腔鱗狀細胞癌

並列摘要

Oral cancer has become a serious health issue in Taiwan. According to previous studies, there is a significant increase of TNF-α in the serum of the oral squamous cell carcinoma (SCC) patient. Besides, the mRNA expression of TNF-α were also elevated significantly in peripheral mononuclear cells from the SCC patients. We designed this study to investigate the genetic differences in the TNF-α promoter polymorphisms of the oral SCC patients, and to determine the role of gene polymorphisms for TNF-α in oral SCC.
　　158 oral SCC male patients and 111 male members of Kaohsiung cleaning squad were enrolled. Venous blood was collected from every case after informed consent. Promoter polymorphisms of TNF-α at position -238, -308, and -1031 were determined by PCR-RFLP.
　　There was no significant difference in the distribution of TNF-α promoter -238G/A, but not -308G/A and -1031T/C. Based on our results, the -238AA genotype did not exist either in the cancer group or in the health group. There was a significant difference in the genotype distribution of -1031, but the conditions were corresponding. The -308A allele frequency was significantly higher in the SCC group than in the health group. -308G may have some kind protective mechanism against to oral SCC, but in contrast -308A may be promotive to oral SCC. Regardless betel quid, cigarette, or alcohol use, there was a significant difference only in -308A. In the non-smoking group, it was the first time for -238A to reveal a significant difference. The polymorphisms of -308 and -1031 are risk factors of oral SCC.

並列關鍵字

TNF-alpha ； polymorphism ； oral cancer

參考文獻

1. 中華民國行政院衛生署統計資訊網, http://www.doh.gov.tw/statistic/index.htm

2. Aderka D, Englemann H, Hornik V, et al.: Increased serum levels of soluble receptors for tumor necrosis factor in cancer patients. Cancer Res 1991; 51(20): 5602-5607.

3. Ardizzoia A, Lissoni P, Brivio F.: Tumor necrosis factor in solid tumors: increases blood levels in the metastatic diaease. J. Biol. Regul. Homeost. Agents 1992; 6: 103-107.

4. Abrahamsson J, Carlsson B, Mellander L.: Tumor necrosis factor-alpha in malignant disease. Am J Pediatr Hematol Oncol 1993; 15: 364-369.

5. Nakashima J, Tachibana M, Ueno M.: Association between tumor necrosis factor in serum and cachexia in patients with prostate cancer. Clin Cancer Res 1998; 53: 1743-1748.