細胞激素之基因多型性與口腔癌及癌前病變之相關性

Cytokine Polymorphisms and the Relation of Oral Cancer and Oral Potentially Malignant Disorders

許瀚仁(Han-Jen Hsu)

指導教授 ： 柯政全

共同指導教授 ： 謝天渝(Tien-Yu Shieh)

高雄醫學大學/口腔醫學院/牙醫學研究所/博士(2014年)

摘要

口腔癌是全世界發生率排名第六之癌症，每年有三十萬個新診斷之病例。在台灣，口腔癌是男性癌症死因中之第四位。雖然流行病學研究中發現嚼食檳榔及抽菸為口腔癌之重要危險因子，但是疾病的發生率並不高，大多數嚼食檳榔及抽菸的人並未罹病，基因型的不同可能能夠解釋其個別的差異。
細胞激素是發炎反應中重要的調節因子，和腫瘤的發生及預後具有其相關性。有許多研究顯示癌症的發生及預後和細胞激素的基因多型性相關。我們的研究是假設細胞激素之基因多型性與口腔癌及口腔黏膜癌前病變的發生及預後相關。
收案期間為2005年四月份至2006年11月，共蒐集高雄醫學大學附設中和紀念醫院口腔顎面外科162名口腔癌病患及42名口腔黏膜癌前病變之病人。另外再共118名健康對照組。以問卷調查方式取得口腔癌及口腔黏膜癌前病變之病患其個人基本資料及相關危險因子。之後，抽取血液檢測其TNF-α、IFN-γ、TGF-β1、 IL-6、與 IL-10之基因多型性，了解此細胞激素之基因多型性和口腔黏膜疾病之發生的相關性，並進行五年的存活率追蹤，以研究口腔癌之癒後及存活率是否與細胞激素的基因多型性相關。 結果:在影響口腔癌及口腔黏膜癌前病變的危險因子研究上，除了菸、酒及檳榔為疾病發生的危險因子外， TGF-β1及 IL-6之基因多型性和口腔黏膜癌前病變之發生之發生具相關性；IL-6、TGF-β1、IL-10及TNF-α之基因多型性則和口腔癌的發生具相關性。在五年存活率之分析研究上，基因多型性與存活率並無顯著相關性。

關鍵字

細胞激素 ； 基因多型性 ； 口腔癌 ； 口腔黏膜癌前病變

並列摘要

Oral cancer (OC) is the sixth most common cancer in the world with approximately 300,000 new cases diagnosed annually. In Taiwan, this disease is one of the malignancies with the most rapidly increasing incidence and the leading cause of death from cancer in men. The available epidemiological evidence indicates that the chewing of the area nut and smoking of cigarette are the important risk factors for OC；however the prevalence rate to develop the OC was relatively low compared with the high frequency of areca nut chewing and cigarette smoking . Genetic predisposition might explain such an individual variability.
Immune system is a complex function for the host defense against biologic, chemical, physical, and irritants. The association between cytokine gene polymorphisms with cancer was investigated. We hypothesized that the risk and prognosis of oral potentially malignant disorders (OPMD) and oral cancer (OC) might be associated with cytokine gene polymorphisms.
A total of 162 OC and 42 OPMD patients treated at the department of Oral and Maxillo-facial Surgery of Chung-Ho Memorial Hospital, Kaohsiung Medical University in Kaohsiung, Taiwan were recruited for this study with informed consent between April 2005 and November 2006. The healthy control group comprised 118 consecutive volunteers who attended a yearly health check-up. We collected data on demographics, the history of exposure to risk factors such as betel quid chewing, cigarette smoking and alcohol drinking with a standard questionnaire for each study subject.
We analyzed eight polymorphisms in five different cytokine genes [IFN-γ (+874 T/A), TGF-s1 (codon 10 T/C and 25 G/C), TNF-α (-308 G/A), IL-6 (-174G/C) and IL-10 (-1082 A/G,-819 T/C,-592 A/C) ]. Allele and genotype data were analyzed for significance of differences between cases and controls
Result: The IL-6, TGF-s1, and TNF-α gene polymorphisms may have a significant association on the development of OPMD. The polymorphisms in IL-6, TNF-α, TGF-β1, and IL-10 and may also have a significant influence on the development of OC. Those polymorphisms are not associated with 5-year survival in patients with OC.

並列關鍵字

cytokine ； polymorphism ； oral cancer ； oral potentially malignant diseases

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